Practical considerations for the evaluation and management of Attention Deficit Hyperactivity Disorder (ADHD) in adults.

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.

Marfan-like habitus and familial adenomatous polyposis in two unrelated males: a significant association?

Familial adenomatous polyposis (FAP) can be considered as a condition of the whole body as extracolonic features derived from all the three embryonic lineages are recorded with varying frequency in addition to the presence of multiple adenomas in the large intestine. Here, we describe two unrelated cases of FAP with unusual extracolonic phenotypes, namely several abnormalities of mesodermal origin strongly resembling Marfan syndrome (MFS) or a Marfan-like habitus. Conventional cytogenetic and FISH analysis did not reveal any gross chromosomal rearrangement on the long arm of chromosome 5 where the APC and FBN2 genes were located. However, in case 2 the FAP-causing mutation in the APC gene was found in the donor splice site of exon 4 and was shown to result in a frameshift and a premature termination codon. We propose that such connective tissue abnormalities may result from germline APC mutations in combination with specific genetic and/or environmental modifying factors.

Aspects of ankylosing spondylarthritis immunopathogenesis correlated with some immunoseric- and synovial parameters in the investigation of histopathological and electronmicroscopic alterations of the articular cartilage correlated with some immunoseric and synovial parameters.

Eighteen biopsies of articular cartilage taken intraoperatory from patients with Ankylosing Spondylarthritis (AS) and from others with traumatisms (controls) were investigated using histopathological (HE, VG, PAS-Alcian, Gömöri, Safranin 0), electronmicroscopic and histoenzymamologic techniques. Histopathologically, the synovitis in AS is characterized by abundant synovia lymphoplasmocytic infiltrates associated with aspects of vascular hyperplasia and fibrosis. At the pannus synovia-cartilage junction we found the invasive synovia lymphoplasmocytic infiltrates. The proteoglycan (PG) depletion is confirmed histopathologically by diminishing the Safranin 0 staining, then ultrastructurally by the existence of collagen revealing areas, whereas biochemically, by the presence of glycosaminoglycans (GAG) in serum and synovial fluid (SF). The morphological data were related to some immunological parameters involved in pathogenesis. In this way, we found pathological values of the immune circulating complexes (ICC) (serum, mean = 73.5 U; SF mean = 81.80 U) and of anti Collagen II antibodies (serum mean = 410 U; SF mean = 436 U). The reactive protein C acting in the phase (CRP) showed high pathological values both in serum (mean = 5.01 mg%) and in SF (mean = 3.6 mg%) of the patients with AS, emphasizing the inflammatory characteristics of the rheumatic disease. The presence of ICC, anticollagen II antibodies and GAS as well in synovia suggests that the inflammatory articulation in AS is a local potential antigen of collagen and proteoglycan nature.

Aspects of immunopathogenesis of rheumatoid arthritis correlated with some immunological parameters in histopathological and electronmicroscopical investigations of the articular cartilage.

The histopathological (H. E., V. G., PAS-Alcian, Safranine 0, Gömöri) and electron-microscopical investigations were carried out on twenty samples of articular cartilage taken during operations from patients with Rheumatoid Arthritis (R. A.) and from others with traumatism, as controls. Histopathologically, the rheumatoid synovial membrane is characterized by synovitis with abundant perivascular lymphoplasmocytic infiltrates. At the pannus synovia-cartilage junction we found the invasive and destructive inflammatory infiltrates penetrating and eroding the cartilage. The histopathological characteristics of the rheumatoid articular cartilage lie in alteration of tinctorial activity, affection of reticuline collagen network and the presence of superficial and deep cartilaginous fissures. The histopathological alterations were confirmed ultrastructurally. Immunologically we found pathological serum values regarding the immune circulating complexes (I. C. C.) (mean = 104 +/- 1.04 U), anticollagen II antibodies (mean = 538 +/- 5 U), reactive Protein C (mean = 16.75 +/- 1.95 mg%) and orosomucoid (mean = 151.1 +/- 4.91 mg%), in seropositive R. A. The corroboration of histopathological, electronmicroscopical and immunological data show the inflammatory and autoimmune feature of this rheumatic disease.

Some humoral immunological aspects of the rheumatoid arthritis correlated with the ultrastructural changes of the rheumatoid synovial fluid.

We performed serologic and synovial investigations in rheumatoid (Latex 1/1280, 1/640, negative and Waaler Rose 1/1024, 1/512, negative), non-rheumatoid and control lots. The immunological results were correlated with ultrastructural changes found in the synovial fluid (SF) at the same titres of rheumatoid factor (RF). The pathologic values of the circulating immune complexes (CIC) (mean = 108.05 U), IgM (mean = 420 UI/ml), IgG (mean = 355.36 UI/ml), and anti-collagen II antibodies (mean = 558.6 U) were present at high titres of RF (Latex 1/1280, Waaler Rose 1/1024). These cases had also major ultrastructural changes of the nucleus and cytoplasm. We inferred from this the implication of the immune factors in the etiology and pathology of the Rheumatoid Arthritis (RA). The high, titres of RF were correlated with pathologic values of the C-reactive-protein (CRP) (mean = 13.31 mg%) and alpha-1-acid glycoprotein (A-1-GA) (mean = 158.3 mg%). The decline of the complement fraction C3 from the synovial fluid in RA confirms the immune character of the rheumatoid synovitis and may be useful in the diagnosis process. The significantly lower concentrations of the protease inhibitors alpha-1-anti-trypsin (A-1-AT) (mean = 165.1 mg%) and alpha-2-macroglobulin (A-2-M) (mean = 129.6 mg%) in synovial fluid suggest a diminution of the anti-proteasic activity due to local immune conflict.

Cytomorphological, ultrastructural and immunological particularities of the synovial fluid in seronegative rheumatoid arthritis.

Our studies on the cytomorphological and ultrastructural analysis of 15 Synovial Fluid (SF) samples from patients diagnosed with seronegative Rheumatoid Arthritis (RA) and 10 SF from patients with Hydroarthrosis considered as controls were carried out. By cytomorphological studies we determined the cellularity, ragocytosis and synoviocytogram. SF in seronegative RA is characterized by leucocytosis (7,656/mm3) with polynucleosis (65.38%) and ragocytosis (59.27%) versus hydroarthrosis SF defined morphologically by lymphocytosis (47%). Degenerative forms of ragocyte-like polymorphonuclears (PMN) cells, individualized by an ultrastructural alteration less evident than recorded in seropositive Rheumatoid Arthritis (RA), associated with a remarkable capacity of endocytosis. The ultrastructural alterations, immune complexes (CIC), the immunoglobulins (MG) and the anticollagen II antibodies, suggest the early implication of these immune parameters in etiopathogenesis. The corroboration of the cytomorphological, ultrastructural and immunological data allows the profound study of the etiopathogenic mechanism and may represent a paraclinical criterion for differentiated seronegative RA field.

[Alpha 1-antitrypsin, alpha 2-macroglobulin and reactive protein C in gastric cancer]. / Alfa 1 antitripsina, alfa 2 macroglobulina si proteina C reactiva în cancerul gastric.

Proteins of acute phase: alpha 1-antitrypsin (AAT), alpha 2-macroglobulin (AMG), reactive C protein (RCP) were determined in the serum of 50 patients with gastric cancer. The Mancini, simple radial immunodiffusion method was used (SRID). The concentration of these proteins increased at 32/50 (64%) for AAT; 30/50 (60%) for AMG and 33/50 (66%) for RCP. By cumulative evaluation, the positivity of serum markers increased to 88%. The importance of differential diagnosis with regard to the benign gastric lesions (adenoma, ulcer, segmentary fibrosis, before receiving the bioptic result, is emphasized.