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1.
Addict Biol ; 29(4): e13392, 2024 04.
Artigo em Inglês | MEDLINE | ID: mdl-38564607

RESUMO

Suicide attempts (SA) are prevalent in substance use disorders (SUD). Epigenetic mechanisms may play a pivotal role in the molecular mechanisms of environmental effects eliciting suicidal behaviour in this population. Hypothalamic-pituitary-adrenal axis (HPA), oxytocin and neurotrophin pathways have been consistently involved in SA, yet , their interplay with childhood adversity remains unclear, particularly in SUD. In 24 outpatients with SUDs, we examined the relation between three parental dysfunctional styles and history of SA with methylation of 32 genes from these pathways, eventually analysing 823 methylation sites. Extensive phenotypic characterization was obtained using a semi-structured interview. Parental style was patient-reported using the Measure of Parental Style (MOPS) questionnaire, analysed with and without imputation of missing items. Linear regressions were performed to adjust for possible confounders, followed by multiple testing correction. We describe both differentially methylated probes (DMPs) and regions (DMRs) for each set of analyses (with and without imputation of MOPS items). Without imputation, five DMRs in OXTR, CRH and NTF3 significantly interacted with MOPS father abuse to increase the risk for lifetime SA, thus covering the three pathways. After imputation of missing MOPS items, two other DMPs from FKBP5 and SOCS3 significantly interacted with each of the three father styles to increase the risk for SA. Although our findings must be interpreted with caution due to small sample size, they suggest implications of stress reactivity genes in the suicidal risk of SUD patients and highlight the significance of father dysfunction as a potential marker of childhood adversity in SUD patients.


Assuntos
Transtornos Relacionados ao Uso de Substâncias , Tentativa de Suicídio , Humanos , Criança , Sistema Hipotálamo-Hipofisário , Sistema Hipófise-Suprarrenal , Pais , Transtornos Relacionados ao Uso de Substâncias/genética , Epigênese Genética
2.
Eur J Haematol ; 107(2): 190-201, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34288162

RESUMO

BACKGROUND: A high prevalence of pulmonary embolism (PE) has been described during COVID-19. Our aim was to identify predictive factors of PE in non-ICU hospitalized COVID-19 patients. METHODS: Data and outcomes were collected upon admission during a French multicenter retrospective study, including patients hospitalized for COVID-19, with a CT pulmonary angiography (CTPA) performed in the emergency department for suspected PE. Predictive factors significantly associated with PE were identified through a multivariate regression model. RESULTS: A total of 88 patients (median [IQR] age of 68 years [60-78]) were analyzed. Based on CTPA, 47 (53.4%) patients were diagnosed with PE, and 41 were not. D-dimer ≥3000 ng/mL (OR 8.2 [95% CI] 1.3-74.2, sensitivity (Se) 0.84, specificity (Sp) 0.78, P = .03), white blood count (WBC) ≥12.0 G/L (29.5 [2.3-1221.2], Se 0.47, Sp 0.92, P = .02), and ferritin ≥480 µg/L (17.0 [1.7-553.3], Se 0.96, Sp 0.44, P = .03) were independently associated with the PE diagnosis. The presence of the double criterion D-dimer ≥3000 ng/mL and WBC ≥12.0 G/L was greatly associated with PE (OR 21.4 [4.0-397.9], P = .004). CONCLUSION: The white blood count, the D-dimer and ferritin levels could be used as an indication for CTPA to confirm PE on admission in non-ICU COVID-19 patients.


Assuntos
COVID-19/complicações , Ferritinas/metabolismo , Produtos de Degradação da Fibrina e do Fibrinogênio/metabolismo , Contagem de Leucócitos , Embolia Pulmonar/sangue , Embolia Pulmonar/complicações , COVID-19/virologia , França , Humanos , Admissão do Paciente , Estudos Retrospectivos , SARS-CoV-2/isolamento & purificação
4.
Therapie ; 73(3): 185-191, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29395300

RESUMO

BACKGROUND: To compare the steady state plasma concentrations (Css) of three antiretroviral drugs in both normal and overweight patients, and to determine the relationship between Css and fat mass (FM) or lean body mass. METHODS: Patients treated for more than 6 months once daily with one of the antiretroviral drugs: efavirenz (EFV) 600mg, atazanavir boosted with ritonavir (ATV-r) 300mg/100mg, or darunavir boosted with ritonavir (DRV-r) 800mg/100mg, combined with two nucleoside analogues, were enrolled prospectively. One at steady state, plasma samples for the assessment of drug concentration were taken and body composition was assessed by bioelectrical impedance. RESULTS: One hundred and thirty-nine patients were enrolled (46, 45 and 48 in the groups EFV, ATV-r and DRV-r respectively). Their mean age was 46.2±10.4 years, 58% were male, 55.4% were from Sub Sahara African (SSA); body mass index (BMI) was 25.4±4.4kg/m2. Mean drug plasma Css of the three drugs did not differ according to BMI group. DRV-r Css tended to be higher in patients with BMI≥25kg/m2 (2896.7±1689 versus 2091.9±1038, P=0.09) and was significantly correlated with FM (r=0.3, P=0.02). In subgroup analysis, the effect of FM on DRV-r Css was significant in patients from SSA (r=0.4, P=0.04). CONCLUSIONS: Css result from many factors and body composition has been shown to only weakly influence interindividual variability but should be investigated in morbidly obese patients treated with DRV-r.


Assuntos
Fármacos Anti-HIV/farmacocinética , Sulfato de Atazanavir/farmacocinética , Benzoxazinas/farmacocinética , Composição Corporal/fisiologia , Peso Corporal/fisiologia , Darunavir/farmacocinética , Adulto , Idoso , Alcinos , Ciclopropanos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Sobrepeso/metabolismo
5.
Pharmacol Res ; 118: 82-92, 2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-27693910

RESUMO

An interaction of drug with food, herbs, and dietary supplements is usually the consequence of a physical, chemical or physiologic relationship between a drug and a product consumed as food, nutritional supplement or over-the-counter medicinal plant. The current educational review aims at reminding to the prescribing physicians that the most clinically relevant drug-food interactions may not be strictly limited to those with grapefruit juice and with the Saint John's Wort herbal extract and may be responsible for changes in drug plasma concentrations, which in turn decrease efficacy or led to sometimes life-threatening toxicity. Common situations handled in clinical practice such as aging, concomitant medications, transplant recipients, patients with cancer, malnutrition, HIV infection and those receiving enteral or parenteral feeding may be at increased risk of drug-food or drug-herb interactions. Medications with narrow therapeutic index or potential life-threatening toxicity, e.g., the non-steroidal anti-inflammatory drugs, opioid analgesics, cardiovascular medications, warfarin, anticancer drugs and immunosuppressants may be at risk of significant drug-food interactions to occur. Despite the fact that considerable effort has been achieved to increase patient' and doctor's information and ability to anticipate their occurrence and consequences in clinical practice, a thorough and detailed health history and dietary recall are essential for identifying potential problems in order to optimize patient prescriptions and drug dosing on an individual basis as well as to increase the treatment risk/benefit ratio.


Assuntos
Citrus paradisi , Interações Alimento-Droga , Sucos de Frutas e Vegetais , Interações Ervas-Drogas , Hypericum , Inibidores do Citocromo P-450 CYP3A/farmacologia , Suplementos Nutricionais , Humanos , Transportador 1 de Ânion Orgânico Específico do Fígado/antagonistas & inibidores , Micronutrientes/administração & dosagem , Farmacovigilância , Varfarina/farmacologia
6.
Pharmacol Res ; 118: 64-70, 2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-27609660

RESUMO

The purpose of the present work was to study the change in morphine metabolic ratio in obese subjects before and after Roux-en-Y Gastric Bypass (RYGB) and to identify clinical and/or biological factors associated with this change. The pharmacokinetics (PK) of oral morphine (30mg), morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G) was performed in patients before (n=25; mean BMI=43.2 (35.4-61.9)kg/m2), 7-15days (n=16) and 6 months after RYGB (n=19; mean BMI=32.3 (25.4-46.0)kg/m2). Morphine Cmax and AUC0-inf were significantly increased and morphine Tmax significantly shortened at 6 months after RYGB compared with preoperative data, indicating an important increase in the rate and extent of morphine absorption. The morphine metabolic ratio 0-inf M3G+M6G/Morphine, decreased significantly from the preoperative to 6 months postoperative period with an average of -26% (range -74%; +21%; p=0.004), but not in the immediate post-operative period. The change in morphine metabolic ratio was associated with a change in BMI, fat mass in kg, and triglyceride levels (rho=0.5, p≤0.04). The degree of change in several markers of low-grade inflammation, or the level of liver steatosis and fibrosis before surgery, was not associated with the change in morphine metabolic ratios. Our findings indicate that RYGB-induced weight loss significantly decreases morphine metabolic ratio, arguing for an effect of morbid obesity on glucuronidation. With glucuronide exposure at 6 months similar to preoperative values, a higher morphine AUC0-inf should encourage reducing morphine dosage in patients undergoing RYGB and chronically receiving immediate-release oral morphine.


Assuntos
Derivados da Morfina/metabolismo , Morfina/metabolismo , Obesidade Mórbida/metabolismo , Feminino , Derivação Gástrica , Humanos , Masculino , Obesidade Mórbida/cirurgia
7.
Mol Pharm ; 13(3): 766-73, 2016 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-26751618

RESUMO

The objective of our work was to study the association between the jejunal expression levels of P-gp, MRP2, MRP3, UGT2B7, CYP3A4, the ABCB1 c.3435C > T polymorphism, and several obesity-associated biomarkers, as well as oral morphine and glucuronides pharmacokinetics in a population of morbidly obese subjects. The pharmacokinetics of oral morphine (30 mg) and its glucuronides was performed in obese patients candidate to bariatric surgery. A fragment of jejunal mucosa was preserved during surgery. Subjects were genotyped for the ABCB1 single nucleotide polymorphism (SNP) c.3435C > T. The subjects were 6 males and 23 females, with a mean body mass index of 44.8 (35.4-61.9) kg/m(2). The metabolic ratios AUC0-inf M3G/morphine and AUC0-inf M6G/morphine were highly correlated (rs = 0.8, p < 0.0001) and were 73.2 ± 24.6 (34.7-137.7) and 10.9 ± 4.1 (3.8-20.6). The pharmacokinetic parameters of morphine and its glucuronides were not associated with the jejunal contents of P-gp, CYP3A4, MRP2, and MRP3. The jejunal content of UGT2B7 was positively associated with morphine AUC0-inf (rs = 0.4, p = 0.03). Adiponectin was inversely correlated with morphine Cmax (rs = -0.44, p = 0.03). None of the factors studied was associated with morphine metabolic ratios. The interindividual variability in the jejunal content of drug transporters and metabolizing enzymes, the ABCB1 gene polymorphism, and the low-grade inflammation did not explain the variability in morphine and glucuronide exposure. High morphine metabolic ratio argued for an increased morphine glucuronidation in morbidly obese patients.


Assuntos
Analgésicos Opioides/farmacocinética , Biomarcadores/análise , Glucuronídeos/farmacocinética , Jejuno/metabolismo , Morfina/farmacocinética , Obesidade Mórbida/metabolismo , Subfamília B de Transportador de Cassetes de Ligação de ATP/genética , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo , Administração Oral , Adolescente , Adulto , Analgésicos Opioides/administração & dosagem , Índice de Massa Corporal , Citocromo P-450 CYP3A , Feminino , Glucuronídeos/administração & dosagem , Glucuronosiltransferase/metabolismo , Humanos , Jejuno/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Morfina/administração & dosagem , Proteína 2 Associada à Farmacorresistência Múltipla , Proteínas Associadas à Resistência a Múltiplos Medicamentos/metabolismo , Obesidade Mórbida/tratamento farmacológico , Polimorfismo de Nucleotídeo Único/genética , Distribuição Tecidual , Adulto Jovem
8.
Mol Pharm ; 13(8): 2631-40, 2016 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-27347605

RESUMO

Protein expression levels of drug-metabolizing enzymes and transporters in human jejunal tissues excised from morbidly obese subjects during gastric bypass surgery were evaluated using quantitative targeted absolute proteomics. Protein expression levels of 15 cytochrome P450 (CYP) enzymes, 10 UDP-glucuronosyltransferase (UGT) enzymes, and NADPH-P450 reductase (P450R) in microsomal fractions from 28 subjects and 49 transporters in plasma membrane fractions from 24 of the same subjects were determined using liquid chromatography-tandem mass spectrometry. Based on average values, UGT1A1, UGT2B15, UGT2B17, SGLT1, and GLUT2 exhibited high expression levels (over 10 fmol/µg protein), though UGT2B15 expression was detected at a high level in only one subject. CYP2C9, CYP2D6, CYP3A5, UGT1A6, P450R, ABCG2, GLUT5, PEPT1, MCT1, 4F2 cell-surface antigen heavy chain (4F2hc), LAT2, OSTα, and OSTß showed intermediate levels (1-10 fmol/µg protein), and CYP1A1, CYP1A2, CYP1B1, CYP2C18, CYP2C19, CYP2J2, CYP3A7, CYP4A11, CYP51A1, UGT1A3, UGT1A4, UGT1A8, UGT2B4, ABCC1, ABCC4, ABCC5, ABCC6, ABCG8, TAUT, OATP2A1, OATP2B1, OATP3A1, OATP4A1, OCTN1, CNT2, PCFT, MCT4, GLUT4, and SLC22A18 showed low levels (less than 1 fmol/µg protein). The greatest interindividual difference (364-fold) was detected for UGT2B17. However, differences in expression levels of other quantified UGTs (except UGT2B15 and UGT2B17), CYPs (except CYP1A1 and CYP3A5), and P450R, and all quantified transporters, were within 10-fold. Expression levels of CYP1A2 and GLUT4 were significantly correlated with body-mass index. The levels of 4F2hc showed significant gender differences. Smokers showed increased levels of UGT1A1 and UGT1A3. These findings provide a basis for understanding the changes in molecular mechanisms of jejunal metabolism and transport, as well as their interindividual variability, in morbidly obese patients.


Assuntos
Sistema Enzimático do Citocromo P-450/metabolismo , Glucuronosiltransferase/metabolismo , Jejuno/metabolismo , Obesidade Mórbida/metabolismo , Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/metabolismo , Citocromo P-450 CYP2C9/metabolismo , Citocromo P-450 CYP2D6/metabolismo , Citocromo P-450 CYP3A/metabolismo , Feminino , Transportador de Glucose Tipo 2/metabolismo , Transportador de Glucose Tipo 5/metabolismo , Humanos , Técnicas In Vitro , Intestino Delgado/metabolismo , Masculino , Antígenos de Histocompatibilidade Menor/metabolismo , Proteínas de Neoplasias/metabolismo , Transportadores de Ânions Orgânicos/metabolismo , Transportador 1 de Peptídeos , Transportador 1 de Glucose-Sódio/metabolismo , Simportadores
10.
Br J Clin Pharmacol ; 79(6): 967-77, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25556837

RESUMO

AIMS: Methadone is characterized by wide intersubject variability regarding the dose needed to obtain full therapeutic response. We assessed the influence of sociodemographic, ethnic, clinical, metabolic and genotypic variables on methadone maintenance dose requirement in opioid-dependent responder patients. METHODS: Eighty-one stable patients (60 men and 21 women, 43.7 ± 8.1 years old, 63.1 ± 50.9 mg day(-1) methadone), divided into quartiles with respect to the median daily dose, were enrolled and underwent clinical examination, treatment history and determination of liver/intestinal cytochrome P450 (CYP) 3A4 activity measured by the midazolam test, R,S-methadone trough concentration and clinically significant polymorphisms of the OPRM1, DRD2, COMT, ABCB1, CYP2B6, CYP3A5, CYP2C19 and CYP2D6 genes. RESULTS: Methadone maintenance dose was correlated to the highest dose ever used (r(2) = 0.57, P < 0.0001). Fractioned methadone intake (odds ratio 4.87, 95% confidence interval 1.27-18.6, P = 0.02), bodyweight (odds ratio 1.57, 95% confidence interval 1.01-2.44, P = 0.04), history of cocaine dependence (80 vs. 44 mg day(-1) in never-addict patients, P = 0.005) and ethnicity (Asian > Caucasian > African, P = 0.04) were independently associated with high-dose methadone in multiple regression analysis. A modest correlation was observed between liver/intestinal CYP3A4 activity and methadone dose at steady state (Spearman rank correlation coefficient [rs ] = 0.21, P = 0.06) but not with highest dose ever used (rs = 0.15, P = 0.18) or dose-normalized R,S-methadone trough concentrations (rs = -0.05, P = 0.64). Concomitant CYP3A4 inhibitors only affected the relationship between methadone dose and R,S-methadone trough concentration. None of the genetic polymorphisms explored was predictive of the methadone maintenance dose. CONCLUSIONS: Methadone maintenance dose was predicted by sociodemographic and clinical variables rather than genetic polymorphisms or liver/intestinal CYP3A4 activity in stable patients.


Assuntos
Analgésicos Opioides/administração & dosagem , Cálculos da Dosagem de Medicamento , Usuários de Drogas , Dependência de Heroína/tratamento farmacológico , Intestinos/enzimologia , Fígado/enzimologia , Metadona/administração & dosagem , Tratamento de Substituição de Opiáceos , Polimorfismo de Nucleotídeo Único , Polimedicação , Adulto , Analgésicos Opioides/efeitos adversos , Analgésicos Opioides/farmacocinética , Biotransformação/genética , Citocromo P-450 CYP3A/genética , Citocromo P-450 CYP3A/metabolismo , Inibidores do Citocromo P-450 CYP3A/efeitos adversos , Interações Medicamentosas , Monitoramento de Medicamentos , Etnicidade , Feminino , França/epidemiologia , Frequência do Gene , Genótipo , Dependência de Heroína/enzimologia , Dependência de Heroína/etnologia , Dependência de Heroína/genética , Humanos , Masculino , Metadona/efeitos adversos , Metadona/farmacocinética , Pessoa de Meia-Idade , Razão de Chances , Farmacogenética , Fenótipo , Estudos Prospectivos , Fatores de Risco
11.
Am J Addict ; 24(7): 613-20, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26331953

RESUMO

BACKGROUND AND OBJECTIVES: The burden of opiate dependence not only relies on somatic complications such as infectious diseases or acute intoxication but also on frequent psychiatric events such as major depressive disorder (MDD) and suicidal behavior (SB). Given the preclinical and clinical evidence regarding the associations between cannabinoid systems and both opiate dependence and psychiatric disorders, we chose to address whether one single nucleotide polymorphism (SNP) of the cannabinoid receptor type 1 gene (CNR1) named rs2023239 would be associated with lifetime MDD and SB in a population of opiate-dependent outpatients remitted under stable methadone treatment. METHODS: Sociodemographic and clinical data were included as independent factors in two logistic regression models aimed at predicting SB and MDD, respectively, performed with 85 Caucasian individuals. RESULTS: The minor C allele of rs2023239 showed an independent protective effect against lifetime MDD after adjustment for potential confounders. It was not associated with variables related to suicidal behavior. CONCLUSIONS AND SCIENTIFIC SIGNIFICANCE: Despite limitations due to the modest sample size, our results are consistent with previous research on the endocannabinoid system and suggest new leads for detecting subjects at risk of MDD, which remains insufficiently diagnosed and treated in patients suffering from severe addictive disorders.


Assuntos
Transtorno Depressivo Maior/complicações , Transtorno Depressivo Maior/genética , Metadona/uso terapêutico , Tratamento de Substituição de Opiáceos , Transtornos Relacionados ao Uso de Opioides/complicações , Transtornos Relacionados ao Uso de Opioides/tratamento farmacológico , Polimorfismo de Nucleotídeo Único/genética , Receptor CB1 de Canabinoide/genética , Adulto , Alelos , Transtorno Depressivo Maior/psicologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Transtornos Relacionados ao Uso de Opioides/genética , Transtornos Relacionados ao Uso de Opioides/psicologia , Pacientes Ambulatoriais/psicologia , Fatores de Proteção , Ideação Suicida , Adulto Jovem
12.
Therapie ; 69(4): 367-81, 2014.
Artigo em Francês | MEDLINE | ID: mdl-24998702

RESUMO

OBJECTIVE: Several surveys have shown a declining performance of French investigators in conducting clinical trials. This is partly due to insufficient and heterogeneous investigator training and site organisation. A multidisciplinary group was set up to propose solutions. We describe the tools developed to improve study site organisation. RESULTS: This working group was made up of clinical research experts from academia, industry, drug regulatory authorities, general practice, and consulting. Methods and tools were developed to improve site organisation. CONCLUSIONS: The proposed tools mainly focus on increasing investigators' awareness of their responsibilities, their research environment, the importance of a thorough feasibility analysis, and the implementation of active patient recruitment strategies. These tools should be able to improve site organisation and performances in conducting clinical trials.


Assuntos
Pesquisa Biomédica/organização & administração , Pesquisa Biomédica/educação , Pesquisa Biomédica/métodos , Pesquisa Biomédica/normas , Protocolos Clínicos/normas , Ensaios Clínicos como Assunto/normas , Comportamento Cooperativo , Estudos de Viabilidade , Humanos , Seleção de Pacientes , Papel Profissional , Registros , Projetos de Pesquisa/normas , Pesquisadores , Responsabilidade Social , Design de Software
15.
Ann Pharmacother ; 47(1): e4, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23324515

RESUMO

OBJECTIVE: To report a case of an overweight man with lymph node tuberculosis due to Mycobacterium bovis, a part of the Mycobacterium tuberculosis complex, treated with fixed-dose combination (FDC) chemotherapy. CASE REPORT: Following guidelines, according to the patient's weight (92 kg), we prescribed the maximum recommended doses of isoniazid-rifampin-pyrazinamide FDC. It led initially to underdosing, with a poor clinical outcome, justifying increased doses and a complex regimen using separate drugs (isoniazid 600 mg, rifampin 1200 mg, and levofloxacin 1000 mg) to achieve therapeutic drug concentrations and clinical response. DISCUSSION: Usually recommended doses of FDC chemotherapies may be inappropriate in overweight patients. We discuss here the different factors that may be involved in poor clinical outcomes, particularly the consequences of excess weight on drug metabolism: drug-drug interaction, FDC use, generic formulation use, intestinal malabsorption, and acetylation profile. CONCLUSIONS: Therapeutic drug monitoring in overweight patients may be useful in the clinical setting to help clinicians individualize drug therapeutic regimens and optimize drug response, adherence, and safety.


Assuntos
Antituberculosos/uso terapêutico , Mycobacterium bovis/isolamento & purificação , Sobrepeso , Tuberculose dos Linfonodos/tratamento farmacológico , Adulto , Antituberculosos/administração & dosagem , Combinação de Medicamentos , Monitoramento de Medicamentos , Quimioterapia Combinada , Humanos , Isoniazida/administração & dosagem , Isoniazida/uso terapêutico , Levofloxacino , Masculino , Ofloxacino/administração & dosagem , Ofloxacino/uso terapêutico , Guias de Prática Clínica como Assunto , Pirazinamida/administração & dosagem , Pirazinamida/uso terapêutico , Rifampina/administração & dosagem , Rifampina/uso terapêutico , Resultado do Tratamento , Tuberculose dos Linfonodos/microbiologia
16.
Front Med (Lausanne) ; 10: 1103752, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36744139

RESUMO

Diagnosis, prognostic assessment, and monitoring disease activity in patients with large vessel vasculitis (LVV) can be challenging. Early recognition of LVV and treatment adaptation is essential because vascular complications (aneurysm, dilatations, ischemic complications) or treatment related side effects can occur frequently in these patients. 18-fluorodeoxyglucose positron emission tomography/computed tomography (2-[18F]FDG-PET/CT) is increasingly used to diagnose, follow, and evaluate treatment response in LVV. In this review, we aimed to summarize the current evidence on the value of 2-[18F]FDG-PET/CT for diagnosis, follow, and treatment monitoring in LVV.

17.
Autoimmun Rev ; 22(4): 103285, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36738953

RESUMO

OBJECTIVE: Hypertrophic pachymeningitis is a rare clinical disorder involving localized or diffuse thickening of the dura mater. Considering pachymeningitis is both in the clinical spectrum of IgG4-RD and ANCA vasculitis (specifically granulomatosis with polyangiitis), an overlap syndrome is discussed. METHODS: We report a case of hypertrophic pachymeningitis revealed by headache and cranial nerve dysfunction, and coexistence of biopsy-proven IgG4-RD pachymeningitis and MPO-ANCA positivity. Furthermore, all cases previously reported in the literature of pachymeningitis with IgG4-RD and presence of ANCA were analyzed. RESULTS: Thirteen patients with pachymeningitis, IgG4-RD and ANCA were analyzed. Patients with HP-related IgG4 and ANCA are mainly male (8, 62%). Median age at diagnosis was 64 years. Main clinical manifestations at diagnosis were localized to the head and neck with headaches (10, 77%), cranial nerve dysfunction (7, 54%), hearing impairment (6, 46%) and vertigo (4, 31%). Except 1 patient with diffuse aortitis, no other systemic manifestation was observed at diagnosis and during follow-up. Serum IgG4 was often elevated (11, 85%) and ANCA was mainly with myeloperoxidase specificity (11, 85%). Seven patients had cerebrospinal fluid analyse with lymphocytic pleocytosis in 5 cases (71%), elevated proteins in 4 cases (57%), positive oligoclonal bands in 3 cases (42%) and decreased glucose in one case (14%). On the MRI, the thickening of the dura mater concerned most often the posterior fossa, in 7 cases (54%). Among 10 cases with histological findings, all showed increased IgG4-positivity of plasma cells, 50% lymphocytic infiltrate but none presented the three major histological criteria of IgG4-related disease. Three (30%) showed histological signs of vasculitis with vascular wall damage and/or giant cells. Among the 12 patients treated with steroid therapy, a clinical improvement was noted in 11 cases (92%). Relapse occurred during tapering in 4 patients (33%). An immunosuppressive drug was added in 2nd line for 7 cases (54%), with a clinical improvement in all. CONCLUSION: Pachymeningitis with IgG4 and ANCA seems a localized disease to the head and neck. Leptomeningeal biopsy commonly found IgG4 criteria and no vasculitis. All patients responded well to steroid therapy and immunosuppressive drugs, especially rituximab, with clinical and radiological improvement but relapse and/or sequelae are not uncommon.


Assuntos
Doença Relacionada a Imunoglobulina G4 , Meningite , Vasculite , Humanos , Masculino , Pessoa de Meia-Idade , Feminino , Doença Relacionada a Imunoglobulina G4/complicações , Doença Relacionada a Imunoglobulina G4/diagnóstico , Anticorpos Anticitoplasma de Neutrófilos , Imunossupressores/uso terapêutico , Vasculite/tratamento farmacológico , Meningite/complicações , Meningite/diagnóstico , Meningite/tratamento farmacológico , Cefaleia , Imunoglobulina G , Recidiva , Esteroides/uso terapêutico
18.
J Clin Med ; 12(22)2023 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-38002732

RESUMO

Concomitant administration of multiple drugs frequently causes severe pharmacokinetic or pharmacodynamic drug-drug interactions (DDIs) resulting in the possibility of enhanced toxicity and/or treatment failure. The activity of cytochrome P450 (CYP) 3A4 and P-glycoprotein (P-gp), a drug efflux pump sharing localization and substrate affinities with CYP3A4, is a critical determinant of drug clearance, interindividual variability in drug disposition and clinical efficacy, and appears to be involved in the mechanism of numerous clinically relevant DDIs, including those involving dexamethasone. The recent increase in the use of high doses of dexamethasone during the COVID-19 pandemic have emphasized the need for better knowledge of the clinical significance of drug-drug interactions involving dexamethasone in the clinical setting. We therefore aimed to review the already published evidence for various DDIs involving dexamethasone in vitro in cell culture systems and in vivo in animal models and humans.

19.
J Clin Med ; 12(13)2023 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-37445384

RESUMO

Inflammatory labyrinthitis is defined as a fluctuant vestibulo-cochlear syndrome associated with an impairment of the blood-labyrinthine barrier (BLB) on delayed FLAIR MRI sequences. Systemic and intratympanic corticosteroids are the gold standard treatment but their effect is frequently insufficient. The objective is here to determine whether infliximab could be of value in the treatment of bilateral inflammatory labyrinthitis. A retrospective monocentric study was conducted between January 2013 and December 2021. All patients included in the study were affected with a bilateral vestibulo-cochlear syndrome associated with bilateral blood-labyrinthine barrier impairment. Patients were administered infliximab at the dose of 5 mg/kg every 6 weeks for 6 months. Audiometry, MRI with delayed FLAIR sequences on the labyrinth, and corticosteroid doses still required were assessed both before and after treatment with infliximab was completed. Pure-tone average (PTA) was the primary outcome. The secondary outcomes were the speech recognition threshold (SRT), the Dizziness Handicap Inventory (DHI) score, and the corticosteroid (CS) dose. A total of nine patients including five men and four women were enrolled in the study. Thirteen ears were analyzed. After a 6-month period of treatment, the mean PTA (54 ± 24 db versus 66 ± 22 db; p = 0.027), SRT (54 ± 37 db versus 66 ± 32 db; p = 0.041) and DHI score (27 ± 15 versus 9 ± 2; p = 0.032) significantly improved. After the 6-month treatment period, the mean CS dose decreased from 38 ± 33 to 6 ± 5 mg/day (p = 0.003). We conclude that infliximab substantially improves the vestibulo-cochlear function in patients with bilateral inflammatory labyrinthitis and could be of value in corticosteroid-dependent cases.

20.
Int Urogynecol J ; 23(12): 1727-34, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-22588140

RESUMO

INTRODUCTION AND HYPOTHESIS: Management of stress urinary incontinence (SUI) with intravaginal devices is an alternative to surgical management, but data of a high level of evidence remain scarce. Our goal was to assess efficacy, tolerance, and acceptability of the 75NC007 intravaginal device for SUI management. METHODS: A phase III, multicenter randomized controlled trial was conducted. After an initial washout period with no treatment, allowing baseline evaluation, women with SUI were randomly assigned to a treatment or control group (no treatment). The primary endpoint was the reduction of incontinence episode frequency (IEF), according to bladder diaries, as compared to baseline. Secondary endpoints were variation of the Urinary Symptom Profile (USP) score, of 24-h pad test, and of CONTILIFE questionnaire scores as compared to baseline. Intent-to-treat and per-protocol analyses were conducted. RESULTS: Fifty-five patients were enrolled and analyzed (26 controls and 29 treated). The mean relative variations of IEF, SUI USP subscore, and overactive bladder (OAB) USP subscore were more significant in the treatment group than in the control group (-31.7 ± 65.1 % vs -7.6 ± 24.5 %, p = 0.002, -2.4 ± 2.6 vs 0.2 ± 2.2, p = 0.004, and -1.5 ± 2.8 vs 0.2 ± 1.8, p = 0.016, respectively). The dysuria USP subscore was slightly decreased in the treatment group. CONTILIFE scores were slightly improved in the treatment group. Pad test variations were not different between groups. No serious adverse event was noted throughout the entire study. CONCLUSIONS: The 75NC007 intravaginal device is a safe and effective noninvasive treatment of SUI in women.


Assuntos
Pessários , Incontinência Urinária por Estresse/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Pessoa de Meia-Idade , Satisfação do Paciente , Pessários/efeitos adversos
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