RESUMO
Attention deficit with or without hyperactivity disorder (ADHD) is one of the most frequent neuropsychiatric disorders, and affects 2-4% of adults. In contrast with many European countries, the identification and management of adult ADHD remains underdeveloped in France, and a subject of controversy. This review provides a practical update on current knowledge about ADHD in adults for French-speaking professionals who have to detect or manage adult patients with ADHD. ADHD is classified as a neurodevelopmental disorder in the recent update of the international diagnostic classification. While symptoms and impairment due to ADHD are frequently severe during childhood, they often evolve as children grow older, with frequent persistent disabilities in adulthood. In adulthood, the clinical presentation, as in childhood, involves the symptom triad of inattention, hyperactivity and impulsivity. However, differences are noted: hyperactivity is more often internalized, symptoms of inattention may be masked by anxiety symptoms or obsessive-like compensation strategies. ADHD is often diagnosed during childhood, but it is not rare for the diagnosis to be made later. Failure to recognise symptoms resulting in misdiagnosis, or alternatively well-developed compensation factors could be two underlying reasons for the long delay until diagnosis. Other symptoms, such as emotional deregulation or executive function-related symptoms are also usually observed in adults. In addition, in adults, ADHD is often associated with other psychiatric disorders (in 80% of cases); this makes the diagnosis even more difficult. These disorders encompass a broad spectrum, from mood disorders (unipolar or bipolar), to anxiety disorders, and other neurodevelopmental disorders and personality disorders, especially borderline and antisocial personality disorder. Substance-use disorders are very common, either as a consequence of impulsivity and emotional dysregulation or as an attempt at self-treatment. Sleep disorders, especially restless leg syndrome and hypersomnolence, could share common pathophysiological mechanisms with ADHD. ADHD and comorbidity-related symptoms are responsible for serious functional impairment, in various domains, leading to academic, social, vocational, and familial consequences. The impact on other psychiatric disorders as an aggravating factor should also be considered. The considerable disability and the poorer quality of life among adults with ADHD warrant optimal evaluation and management. The diagnostic procedure for ADHD among adults should be systematic. Once the positive diagnosis is made, the evaluation enables characterisation of the levels of severity and impairment at individual level. A full examination should also assess medical conditions associated with ADHD, to provide personalized care. In recent years, a growing number of assessment tools have been translated and validated in French providing a wide range of structured interviews and standardized self-report questionnaires for the evaluation of core and associated ADHD symptoms, comorbidities and functional impairment. The treatment of ADHD in adults is multimodal, and aims to relieve the symptoms, limit the burden of the disease, and manage comorbidities. The most relevant and validated psychological approaches are psycho-education, cognitive-behavioural therapy and "third wave therapies" with a specific focus on emotional regulation. Cognitive remediation and neurofeedback are promising strategies still under evaluation. Medications, especially psychostimulants, are effective for alleviating ADHD symptoms with a large effect size. Their safety and tolerance are satisfactory, although their long-term clinical benefit is still under discussion. In France, methylphenidate is the only stimulant available for the treatment of ADHD. Unfortunately, there is no authorization for its use among adults except in continuation after adolescence. Hence the prescription, which is subject to the regulations on narcotics, is off-label in France. This article aims to provide practical considerations for the management of ADHD and associated disorders in adults, in this particular French context.
Assuntos
Transtorno do Deficit de Atenção com Hiperatividade/diagnóstico , Transtorno do Deficit de Atenção com Hiperatividade/terapia , Adulto , Envelhecimento/psicologia , Transtorno do Deficit de Atenção com Hiperatividade/tratamento farmacológico , Transtorno do Deficit de Atenção com Hiperatividade/psicologia , Estimulantes do Sistema Nervoso Central , Humanos , Metilfenidato/uso terapêutico , PsicoterapiaRESUMO
During the last decade, there has been a growing interest in understanding the fate of food during digestion in the gastrointestinal tract in order to strengthen the possible effects of food on human health. Ideally, food digestion should be studied in vivo on humans but this is not always ethically and financially possible. Therefore simple static in vitro digestion models mimicking the gastrointestinal tract have been proposed as alternatives to in vivo experiments but these models are quite basic and hardly recreate the complexity of the digestive tract. In contrast, dynamic models that allow pH regulation, flow of the food and injection in real time of digestive enzymes in the different compartments of the gastrointestinal tract are more promising to accurately mimic the digestive process. Most of the systems developed so far have been compared for their performances to in vivo data obtained on animals and/or humans. The objective of this article is to review the validation towards in vivo data of some of the dynamic digestion systems currently available in order to determine what aspects of food digestion they are able to mimic. Eight dynamic digestion systems are presented as well as their validation towards in vivo data. Advantages and limits of each simulator is discussed. This is the result of a cooperative international effort made by some of the scientists involved in Infogest, an international network on food digestion.
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Biomimética/métodos , Digestão/fisiologia , Alimentos , Técnicas In Vitro , Modelos Biológicos , Animais , Fermentação , Trato Gastrointestinal/fisiologia , Humanos , Concentração de Íons de Hidrogênio , NutrientesRESUMO
OBJECTIVE: Off-label prescription is a common practice in psychiatry, raising health and economic concerns. Collegial consultation could allow a framed prescription of treatments that are not authorized in specific indications. Attention Deficit Hyperactivity in adult populations (ADHD) is a striking example of a pathology where off-label prescription is frequent. First considered to be a childhood disorder, the awareness of this condition in adults is increasing, leading to the development of new clinical practices and treatments. However, the adult ADHD diagnosis and its management are still emerging in France despite a high prevalence. Treatment of adult ADHD relies on methylphenidate prescription, but the initiation of this drug is not authorized in adult populations. Methylphenidate is a central nervous system stimulant that is structurally close to amphetamine and acts as a norepinephrine and dopamine reuptake inhibitor. Due to these pharmacological properties, neuropsychiatric and cardiovascular side-effects could occur. Furthermore, its addictive potential has led France to classify it as a psychoactive drug, dispensed via secured prescription. The first prescription and the one-year follow-up are restricted to neurologists, paediatrics, psychiatrists and sleep disorders specialists at hospital. The objective of this article is to propose a multidisciplinary framework for the off-label prescription of methylphenidate in adult ADHD. METHODS: The Multidisciplinary Advice Consultation for Exceptional Addiction Treatments (Consultation d'Avis Multidisciplinaire de Traitements d'Exception en Addictologie CAMTEA) was first set up in Lille for the prescription of baclofen in alcohol dependence and was then extended to topiramate in binge eating disorder. This procedure has been adapted to the particularities of ADHD in adult populations, the differential diagnosis (bipolar disorder, depressive disorder, anxious disorder, personality disorder, substance use disorder) and the co-morbidities requiring a full psychiatric and neuropsychological assessment. Moreover, a particular attention has been paid to the monitoring of neuropsychiatric, cardiovascular and misuse risk because of the potential side-effects of methylphenidate. RESULTS: The proposed prescription framework is structured into several specialized consultations. A first psychiatric evaluation aims to diagnose adult ADHD, using the French version of the Diagnostisch Interview Voor ADHD 2.0 questionnaire (DIVA 2.0), and to assess the quality of life impact with the Weiss Functional Inventory Rating Scale (WIFRS). It also searches for the presence of differential diagnosis or co-morbidities. The second appointment consists of a pharmacological evaluation that aims to search for contraindications and potential drug interaction. A neuropsychological evaluation based on standardized tests (Weschler Adulte Intelligence Scale [WAIS IV], Conner's Continuous Performance Test 3 [CPT] and the Minnesota Multiphasic Personnality Inventory [MMPI]) is also required to evaluate neurocognitive disabilities and personality features. Once the parameters of the different assessments have been collected, the synthesis is presented during a multidisciplinary meeting in order to assess the risk-benefit ratio for each patient. Several specialties are involved in this multidisciplinary meeting: psychiatry, addictology, general medicine, addictovigilance, pharmacovigilance and neuropsychology. One strategy among three possibilities can be decided: (1) contraindication to treatment with methylphenidate, (2) attention deficit disorder that does not require medication management, and (3) indication of treatment with methylphenidate with the choice of the pharmacological form (immediate or prolonged release). A biological check-up and an electrocardiogram are carried out systematically before any treatment. If the decision is made to initiate treatment, it is started at the lowest dosage and followed by a titration phase. A weekly follow-up is carried out during the titration phase in order to assess treatment efficacy and safety. After treatment stabilization, the general practitioner can carry out the renewal, and the patient will be reassessed within the framework of the multidisciplinary consultation every 3 months. CONCLUSION: When an off-label prescription is being considered, it must comply with the basic rules of good clinical practice, and the benefit/risk ratio should be constantly reassessed. The proposed multidisciplinary framework, adapted to the characteristics of adult ADHD and the pharmacological properties of methylphenidate, appears to be an interesting strategy to meet the requirements of the good clinical practice. The complementary assessments carried out and the collegial framework allow enhancing the patient's follow-up and minimize the drug risk, particularly in the psychiatric, addictive and cardiovascular adverse events. Finally, this framework could also help the monitoring of other off-label treatments for ADHD, such as atomoxetine or guanfacine.
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Transtorno do Deficit de Atenção com Hiperatividade/tratamento farmacológico , Estimulantes do Sistema Nervoso Central/uso terapêutico , Metilfenidato/uso terapêutico , Uso Off-Label , Adulto , Estimulantes do Sistema Nervoso Central/administração & dosagem , Estimulantes do Sistema Nervoso Central/efeitos adversos , Prescrições de Medicamentos , Eletrocardiografia , Feminino , França , Humanos , Masculino , Conduta do Tratamento Medicamentoso , Metilfenidato/administração & dosagem , Metilfenidato/efeitos adversos , Testes Neuropsicológicos , Equipe de Assistência ao Paciente , Escalas de Graduação Psiquiátrica , Encaminhamento e Consulta , Resultado do TratamentoRESUMO
During the last decade, there has been a growing interest in understanding food's digestive fate in order to strengthen the possible effects of food on human health. Ideally, food digestion should be studied in vivo on humans but this is not always ethically and financially possible. Therefore, simple in vitro digestion models mimicking the gastrointestinal tract have been proposed as alternatives to in vivo experiments. Thus, it is no surprise that these models are increasingly used by the scientific community, although their various limitations to fully mirror the complexity of the digestive tract. Therefore, the objective of this article was to call upon the collective experiences of scientists involved in Infogest (an international network on food digestion) to review and reflect on the applications of in vitro digestion models, the parameters assessed in such studies and the physiological relevance of the data generated when compared to in vivo data. The authors provide a comprehensive review in vitro and in vivo digestion studies investigating the digestion of macronutrients (i.e., proteins, lipids, and carbohydrates) as well as studies of the bioaccessibility and bioavailability of micronutrients and phytochemicals. The main conclusion is that evidences show that despite the simplicity of in vitro models they are often very useful in predicting outcomes of the digestion in vivo. However, this has relies on the complexity of in vitro models and their tuning toward answering specific questions related to human digestion physiology, which leaves a vast room for future studies and improvements.
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Digestão/fisiologia , Alimentos , Trato Gastrointestinal/fisiologia , Humanos , Modelos BiológicosRESUMO
INTRODUCTION: Incidence of urolithiasis is increasing in industrialized countries. Amendments can be explained among others by dietary changes. More and more young patients have urolithiasis. The objective of this study was to analyze and update the epidemiology of stones in south of France about age and gender. MATERIAL AND METHODS: A retrospective single-center study from 2009 to June 2015 included all urolithiasis analyzed by infrared spectroscopy. Groups were composed according to the mineral content (oxalocalcic with whewellite and weddelite, calcium phosphate stones, uric acid stones ). RESULTS: A total of 749 stones were analyzed. The sex ratio was 1.96 all aged confused. The most common stones were oxalocalcic (51.3 %), followed mixed stones (21.2 %) and calcium phosphate stones (11.9 %). The calcium oxalate stones are mainly composed of whewellite (42 %) and calcium phosphate stones of carbapatite (18.6 %). The stones of whewellite were more frequent in men (P=0.0009), as well as uric acid stones (P=0.01) and mixed stones in women (P=0.00003), as well as calcium phosphate (P=0.0005). CONCLUSIONS: Epidemiology of stones has changed with an increased incidence in women, and nephrolithiasis patients getting older. A change in the type of stones is observed with increasing the proportion of mixed stones especially among women. Nutritional and metabolic studies are needed to find the etiology of the change in the epidemiology of urolithiasis. LEVEL OF EVIDENCE: 4.
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Urolitíase/epidemiologia , Adolescente , Adulto , Distribuição por Idade , Idoso , Idoso de 80 Anos ou mais , Oxalato de Cálcio , Fosfatos de Cálcio , Criança , Pré-Escolar , Feminino , França/epidemiologia , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Distribuição por Sexo , Ácido Úrico , Adulto JovemRESUMO
Understanding the mechanisms of food digestion is of paramount importance to determine the effect foods have on human health. Significant knowledge on the fate of food during digestion has been generated in healthy adults due to the development of physiologically-relevant in vitro digestion models. However, it appears that the performance of the oro-gastrointestinal tract is affected by ageing and that a model simulating the digestive conditions found in a younger adult (<65 years) is not relevant for an older adult (>65 years). The objectives of the present paper were: (1) to conduct an exhaustive literature search to find data on the physiological parameters of the older adult oro-gastrointestinal tract, (2) to define the parameters of an in vitro digestion model adapted to the older adult. International experts have discussed all the parameters during a dedicated workshop organized within the INFOGEST network. Data on food bolus properties collected in the older adult were gathered, including food particle size found in older adult boluses. In the stomach and small intestine, data suggest that significant physiological changes are observed between younger and older adults. In the latter, the rate of gastric emptying is slowed down, the pH of the stomach content is higher, the amount of secretions and thus the hydrolytic activities of gastric and intestinal digestive enzymes are reduced and the concentration of bile salts lower. The consensus in vitro digestion model of the older adult proposed here will allow significant progress to be made in understanding the fate of food in this specific population, facilitating the development of foods adapted to their nutritional needs. Nevertheless, better foundational data when available and further refinement of the parameters will be needed to implement the proposed model in the future.
Assuntos
Digestão , Modelos Biológicos , Humanos , Idoso , Consenso , Digestão/fisiologia , Trato Gastrointestinal/fisiologia , EstômagoRESUMO
Milk fat secretion is a complex process that initiates in the endoplasmic reticulum of the mammary epithelial cell by the budding of lipid droplets. Lipid droplets are finally released as fat globules in milk enveloped by the apical plasma membrane of the mammary epithelial cell. The milk fat globule membrane (MFGM) thus comprises membrane-specific proteins and polar lipids (glycerophospholipids and sphingolipids) surrounding a core of neutral lipids (mainly triacylglycerols and cholesterol esters). We have recently described major proteins of the MFGM in the goat and we have highlighted prominent differences between goats and bovine species, especially regarding lactadherin, a major MFGM protein. Here, we show that, in the goat species, the well-documented genetic polymorphism at the α(s1)-casein (CSN1S1) locus affects both structure and composition of milk fat globules. We first evidenced that both milk fat globule size and ζ-potential are related to the α(s1)-casein genotype. At midlactation, goats displaying strong genotypes for α(s1)-casein (A/A goats) produce larger fat globules than goats with a null genotype at the CSN1S1 locus (O/O goats). A linear relationship (R(2)=0.75) between fat content (g/kg) in the milk and diameter of fat globules (µm) was established. Moreover, we found significant differences with regard to MFGM composition (including both polar lipids and MFGM proteins) from goats with extreme genotype at the CSN1S1 locus. At midlactation, the amount of polar lipids is significantly higher in the MFGM from goats with null genotypes for α(s1)-casein (O/O goats; 5.97±0.11mg/g of fat; mean ± standard deviation) than in the MFGM from goats with strong genotypes for α(s1)-casein (A/A goats; 3.96±0.12mg/g of fat; mean ± standard deviation). Two MFGM-associated proteins, namely lactadherin and stomatin, are also significantly upregulated in the MFGM from goats with null genotype for α(s1)-casein at early lactation. Our findings are discussed with regard to techno-functional properties and nutritional value of goat milk. In addition, the genetic polymorphism in the goat species appears to be a tool to provide clues to the lipid secretion pathways in the mammary epithelial cell.
Assuntos
Caseínas/genética , Glicolipídeos/química , Glicoproteínas/química , Alelos , Animais , Butirofilinas , Caseínas/química , Feminino , Genótipo , Glicolipídeos/análise , Glicoproteínas/análise , Cabras , Lactação/metabolismo , Gotículas Lipídicas , Lipídeos/análise , Lipídeos/química , Glicoproteínas de Membrana/análise , Proteínas de Membrana/análise , Leite/química , Proteínas do Leite/análise , Proteínas do Leite/química , Valor Nutritivo , Perilipina-2 , Polimorfismo Genético , Eletroforese em Gel Diferencial BidimensionalRESUMO
Some clinical studies have suggested a relationship between allergic diseases and gut microbiota. We aimed to study bifidobacterial colonization at species and strain levels in ten allergic French infants included at their first clinical consultation and 20 controls matching for age at sampling, mode of delivery, per partum antibiotics, type of feeding and antibiotics in the first weeks of life. The faecal microbiota was analyzed by culture methods and TTGE. Bifidobacterial species and strains were identified using multiplex PCR and Box-PCR fingerprinting. No differences were observed between groups in the number of colonized infants or in the levels of colonization by the main aerobic and anaerobic genera. All infants were colonized with high levels of Bifidobacterium except for one in each group. One to 5 Bifidobacterium species and 1 to 7 strains were observed per subject independently of allergic status and age at sampling. Our study showed the infants to be colonized by several species and strains, including several strains from the same species. This diversity in Bifidobacterium colonization was not related with the allergic status and showed that the link between Bifidobacterium colonization and allergic diseases is complex and cannot be restricted to the role attributed to Bifidobacterium species.
Assuntos
Bifidobacterium/genética , Trato Gastrointestinal/microbiologia , Lactente , Bifidobacterium/classificação , Bifidobacterium/crescimento & desenvolvimento , Bifidobacterium/isolamento & purificação , Estudos de Casos e Controles , Pré-Escolar , Fezes/microbiologia , França , Humanos , Hipersensibilidade/diagnóstico , Complexo Antígeno L1 Leucocitário/análise , Modelos Logísticos , Reação em Cadeia da Polimerase/métodos , RNA Bacteriano/genética , RNA Ribossômico 16S/genéticaRESUMO
INTRODUCTION: Skeletal-related events (SRE) are common in patients with bone metastatic lung cancer and have a negative impact on quality of life and survival. The objective of this study is to identify predictive factors for SRE occurrence among this population. METHODS: We conducted a 3-year retrospective study including 100 lung cancer patients with bone metastasis. RESULTS: Eighty-two patients presented at least one SRE (69.5% at baseline). The median occurrence for SRE was 4.5 months and severe bone pain was the most common SRE (56%). The alkaline phosphatase serum level>120IU/L (hazard ratio [sHR]=2.8; 95% confidence interval (CI) [1.5-5.4]; P=0.002) and calcemia>2.6mmol/L ([sHR]=9.7; 95% CI [5.1-18.4]; P<0.001) were identified as risk factors for SRE occurrence while the presence of an initial SRE was associated with a decrease of this risk ([sHR]=0.2; 95% CI [0.1-0.4]; P<0.001). CONCLUSION: The elevated alkaline phosphatase serum level and hypercalcemia are risk factors for SRE occurrence in bone metastatic lung cancer patients and should be used as biomarkers to adapt current medical practice for these patients.
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Neoplasias Ósseas/etiologia , Neoplasias Ósseas/secundário , Carcinoma Broncogênico/patologia , Neoplasias Pulmonares/patologia , Idoso , Neoplasias Ósseas/diagnóstico , Neoplasias Ósseas/epidemiologia , Carcinoma Broncogênico/diagnóstico , Carcinoma Broncogênico/epidemiologia , Carcinoma Broncogênico/terapia , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/epidemiologia , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/terapia , Comorbidade , Feminino , França/epidemiologia , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/epidemiologia , Neoplasias Pulmonares/terapia , Masculino , Pessoa de Meia-Idade , Prognóstico , Qualidade de Vida , Estudos Retrospectivos , Fatores de Risco , Resultado do TratamentoRESUMO
Anaplastic lymphoma kinase (ALK) rearrangement is a therapeutically targetable oncogenic driver found in 5% of patients with non-small-cell lung cancer (NSCLC). The objective of this paper is to synthesise current knowledge on ALK rearrangement and its impact on the management of advanced NSCLC. Several inhibitors of the tyrosine kinase of ALK (crizotinib, ceritinib, alectinib) have been approved as first line therapies in patients with advanced ALK positive NSCLC, which are associated with a better median progression-free survival than conventional chemotherapy. Unfortunately, the emergence of drug resistance leads to tumor progression. In patients with oligoprogressive disease if local ablative therapy can be effected, continuing with the same ALK tyrosine kinase inhibitor is one option. In patients with progression, clinicians may consider switching to another therapy. Rebiopsy of the tumor or liquid biopsy could be attempted to identify the mechanisms of resistance and to customize ALK-target therapy. The emergence of crizotinib drug resistance has prompted the development of next generation drugs including ceritinb, alectinib, brigatinib and lorlatinib. The ability to quickly develop targeted therapies against specific oncogenic drivers will require close co-operation between pathologists, pulmonologists and oncologists in the future to keep pace with drug discoveries and to define optimal therapeutic strategies.
Assuntos
Quinase do Linfoma Anaplásico/genética , Carcinoma Pulmonar de Células não Pequenas/terapia , Neoplasias Pulmonares/terapia , Oncologia/métodos , Antineoplásicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Progressão da Doença , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/genética , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Oncologia/tendências , Terapia de Alvo Molecular/métodos , Terapia de Alvo Molecular/tendências , Estadiamento de Neoplasias , Inibidores de Proteínas Quinases/uso terapêuticoRESUMO
In vitro alternatives to clinical trials are used for studying human food digestion. For simulating infant digestion, only a few models, lacking physiological relevance, are available. Thanks to an extensive literature review of the in vivo infant digestive conditions, a gastrointestinal static in vitro model was developed for infants born at term and aged 28days. The model was applied to the digestion of a commercial infant formula. Kinetics of digestion, as well as the structural evolution, were compared with those obtained while submitting the same formula to the adult international consensus protocol of in vitro static digestion. The kinetics of proteolysis and lipolysis differed according to the physiological stage resulting mainly from the reduced level of enzymes and bile salts, as well as the higher gastric pH in the infant model. This in vitro static model of infant digestion is of interest for scientists, food or pharmaceutical manufacturers.
Assuntos
Digestão , Consenso , Humanos , Lactente , Fórmulas Infantis , Cinética , LipóliseRESUMO
Doege-Potter syndrome is a paraneoplastic syndrome characterized by non-islet cell tumor hypoglycemia secondary to a solitary fibrous tumor. These tumors are rare and usually asymptomatic. The syndrome of hypoglycemia is seen in less than 5% of the cases, and the associated tumors are large with a high mitotic rate. The cause of hypoglycemia is related to insulin-like growth factors produced by these tumors called "big" IGF-2. Several biological tests can demonstrate the increase of "big" IGF-2 plasma levels confirming the diagnosis of non-islet cell tumor induced hypoglycemia. The diagnosis is suggested by imaging but diagnostic confirmation is provided by the surgery, which remains the treatment of choice. Resection in many cases is the cure leading to hypoglycemia resolution. Recurrences and malignant transformations are possible which imposes a long-term monitoring. We report a case with relapsed malignant pleural fibrous tumor for which the pathophysiological mechanism of hypoglycemia could be documented as a paraneoplastic syndrome.
Assuntos
Hipoglicemia/etiologia , Síndromes Paraneoplásicas/etiologia , Neoplasias Pleurais/complicações , Sarcoma/complicações , Idoso , Documentação , Humanos , Hipoglicemia/sangue , Hipoglicemia/patologia , Fator de Crescimento Insulin-Like II/metabolismo , Masculino , Prontuários Médicos , Síndromes Paraneoplásicas/sangue , Síndromes Paraneoplásicas/patologia , Neoplasias Pleurais/sangue , Neoplasias Pleurais/patologia , Sarcoma/metabolismo , Sarcoma/patologiaRESUMO
Carcinoembryonic antigen (CEA) and neuron-specific enolase (NSE) level determinations were carried out by radioimmunoassay in pleural fluid and plasma samples obtained from 24 patients with malignant pleural effusions and 18 patients with non-malignant pleural effusions, and compared to cytological and pathological results. Using a pathological cut-off level of 25 ng/ml for CEA and 8 ng/ml for NSE, we demonstrated that, in the diagnosis of the malignant nature of pleural effusions, the simultaneous quantification of CEA and NSE in pleural fluid possesses better discriminative values than the simultaneous quantification of both markers in plasma or the separate quantification of each marker, in pleural fluid and in plasma.
Assuntos
Biomarcadores Tumorais/análise , Antígeno Carcinoembrionário/análise , Neoplasias Pulmonares/complicações , Fosfopiruvato Hidratase/análise , Derrame Pleural Maligno/etiologia , Humanos , Neoplasias Pulmonares/química , Neoplasias Pulmonares/diagnóstico , Derrame Pleural Maligno/química , Valor Preditivo dos Testes , Estudos ProspectivosRESUMO
Significant tumor stroma development is a specific feature of adenocarcinoma of the lung in comparison to small-cell lung cancer (SCLC). The fibrotic component of tumor stroma is thought to result from the migration and local replication of mesenchymal cells in response to the presence of cytokines. One of them, platelet-derived growth factor (PDGF), is a chemotactic and growth factor for mesenchymal cells. Since several lung adenocarcinoma cell lines, but not SCLC cell lines, have been shown in vitro to express PDGF genes, we evaluated pleural effusions for the presence of PDGF in patients with adenocarcinoma of the lung, SCLC, or nonmalignant pleural effusions. In adenocarcinoma of the lung, PDGF levels in pleural effusions were higher than in SCLC and in nonmalignant pleural effusions and were associated with the presence of a growth-promoting activity for fibroblasts due, in part, to the presence of PDGF. This observation suggests the role of PDGF in tumor stroma formation in adenocarcinoma of the lung.
Assuntos
Adenocarcinoma/metabolismo , Neoplasias Pulmonares/metabolismo , Fator de Crescimento Derivado de Plaquetas/metabolismo , Derrame Pleural Maligno/metabolismo , Idoso , Carcinoma de Células Pequenas/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Derrame Pleural/metabolismoRESUMO
PURPOSE: New endobronchial techniques of treatment allow a good unblocking. Nevertheless, only high dose rate brachytherapy delivers a curative treatment for invasive carcinomas. This study analyses the results of the first 33 consecutive patients treated with curative intent by this technique from 1994 to 1997, and followed-up more than one year. PATIENTS AND METHODS: Thirty-seven lesions were treated, with usual schedule delivering 30 Gy at 1 cm depth in six fractions and three to five weeks. All the patients were meticulously selected on the local involvement of the tumour and absolute contraindications to a surgical treatment. All of them have a pulmonary disease history or a general contraindication. RESULTS: With a 14-month follow-up, the local control at two months after the treatment was 95% (endoscopic and histologic), and 90% of the patients presented a prolonged local control. Four patients died of the treated cancer, another of a controlateral cancer. Ten patients died of another disease, five of them from a respiratory insufficiency. The overall survival rate at two years was 53% and the specific survival rate 80%. The acute tolerance was good, without incident. Asymptomatic bronchial stenoses, described by endoscopic follow-up, were described for seven patients. CONCLUSION: We conclude that, on the basis of a good selection of the patients and a respect of the indications, high dose rate endobronchial brachytherapy is an effective curative treatment. It offers a new curative option and must be proposed for the small invasive carcinomas in non-operable patients.
Assuntos
Braquiterapia , Neoplasias Brônquicas/radioterapia , Seguimentos , Humanos , Dosagem RadioterapêuticaRESUMO
The authors report the case of a neonate who died early of refractory heart failure and presented with all the characteristics of Marfan's syndrome in its early form with articular retractions. There was clinical evidence of mitral, tricuspid and major aortic regurgitation. Two-dimensional and doppler echocardiography confirmed the prolapse of highly dystrophic valves and the quadrivalvar regurgitation. Typical lesions of the connective-elastic tissue were found at autopsy. The occurrence of malignant Marfan's syndrome in neonates seems to be exceptional; the syndrome may take the rare "en contractures" form. Death is not always ascribable to the cardiac pathology, this pathology being often less generalized than in our case which seems to be the first one where such diffuse and massive valval lesions have been observed. This particular form was comparable to the "congenital polyvalvular disease" described by Bahrati and Lev, except that the skeletal and visceral abnormalities of Marfan's syndrome are absent in that disease.
Assuntos
Insuficiência Cardíaca/etiologia , Valvas Cardíacas/anormalidades , Síndrome de Marfan/complicações , Valva Aórtica/anormalidades , Ecocardiografia Doppler , Humanos , Recém-Nascido , Masculino , Valva Mitral/anormalidades , Valva Tricúspide/anormalidadesRESUMO
Fibrosis is a disorder characterized by a qualitative and quantitative alteration of the deposition of extracellular matrix with accumulation of mesenchymal cells in replacement of normal tissue. The sequence of events leading to fibrosis of an organ involves the subsequent processes of injury with inflammation and disruption of the normal tissue architecture, followed by tissue repair with accumulation of mesenchymal cells in this area. A similar sequence of events occurs in wound healing with formation of normal, limited and transient granulation tissue, while in fibrosis, a maladaptive repair leads to an extensive, exaggerated process with functional impairment. Inflammatory cells (mainly mononuclear phagocytes), platelets, endothelial cells, and type II pneumocytes play a direct and indirect role in tissue injury and repair. The evaluation of several human fibrotic lung diseases, five diffuse (idiopathic pulmonary fibrosis (IPF); adult respiratory distress syndrome (ARDS); coal workers' pneumoconiosis (CWP); Hermansky-Pudlak syndrome (HPS); systemic sclerosis (SS)) and two focal (tumour stroma in lung cancer; and obliterative bronchiolitis (OB) after lung transplantation), has shown that several cytokines participate in the local injury and inflammatory reaction (interleukin-1 (IL-1), interleukin-8 (IL-8), monocyte chemotactic protein-1 (MCP-1), and tumour necrosis factor-alpha (TNF-alpha)), while other cytokines are involved in tissue repair and fibrosis (platelet-derived growth factor (PDGF), insulin-like growth factor-1 (IGF-1), transforming growth factor-beta (TGF-beta), and basic-fibroblast growth factor (b-FGF)). A better understanding of the cytokines and cytokine networks involved in lung fibrosis leads to the possibility of new therapeutic approaches.
Assuntos
Citocinas/fisiologia , Fibrose Pulmonar/fisiopatologia , Humanos , Pulmão/fisiopatologia , Fibrose Pulmonar/complicações , Fibrose Pulmonar/patologiaRESUMO
Atrial natriuretic factor (ANF) is a peptide secreted by auricular cardiac cells and acts on the brain; it is a diuretic, a natriuretic and a vasodilator and inhibits the renin angiotensin aldosterone system at several levels. The lungs are rich in specific ANF receptors present both at a vascular cellular level and in the mesothelial cells. These receptors participate in the extraction of ANF during its pulmonary intravascular transit and also in its enzymatic degradation. Endogenous ANF (and exogenous) is a vasodilator of the pulmonary arterial bed, representing a regulatory system for right ventricular afterload and probably modifying pulmonary capillary permeability. Hypoxia and hypercapnia contribute by direct and indirect mechanisms to the stimulation of ANF secretion explaining their elevated levels in pulmonary arterial hypertension and chronic respiratory insufficiency. The lung can under certain conditions synthesise ANF itself as can neuro-endocrine bronchial tumours. ANF may be involved in the understanding of sodium retention during ventilation with PEEP and in the paraneoplastic hyponatraemia of certain bronchial tumours. Finally acute bronchial obstruction leads to hypersecretion of ANF which has some bronchodilator properties.
Assuntos
Fator Natriurético Atrial/fisiologia , Pulmão/fisiologia , Humanos , Pneumopatias/fisiopatologia , Circulação Pulmonar/fisiologiaRESUMO
The authors report a case of a malignant mesothelioma of the left main pleura diagnosed by thoracoscopy and treated by pleural talcage followed with four courses of chemotherapy using cisplatin in a dose of 40 mgms/m2 from days 1 to 5 resulting in a near complete remission for one year. Following a review of the literature the authors analyse the potential value of chemotherapy in this type of tumour whose treatment up to the present time has been particularly disappointing.
Assuntos
Cisplatino/uso terapêutico , Mesotelioma/tratamento farmacológico , Neoplasias Pleurais/tratamento farmacológico , Idoso , Cisplatino/administração & dosagem , Terapia Combinada , Humanos , Masculino , Mesotelioma/radioterapia , Neoplasias Pleurais/radioterapia , Indução de Remissão , Talco/uso terapêuticoRESUMO
In France, sarcoidosis is the most frequent interstitial lung disease of unknown origin. Its prevalence is about 9.5 in 100 000. Almost 30% of the patients require corticosteroid treatment. Although the aetiology remains unknown, detailed concepts of the immunopathogenesis have been suggested. Employing the technique of bronchoalveolar lavage, some immunopathogenic mechanisms have been elucidated and the hypothesis that an unknown causative agent stimulates T-lymphocytes and macrophages by physiological mechanisms has emerged. The activity of these cells maintains the inflammation and is the target of the corticosteroid therapy. By new serologic parameters it is possible to gauge this activity and to document the therapeutic effect.