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Biomedical subjects

E Cogan

Publications and source records attributed to E Cogan.

At least 19 recordsLinked to original sources
PubMed2006

[Side effects of drugs: from unwanted to desirable effects].

The origins of unwanted side effects of drugs may be related to the clinical features of the patient. Indeed, co-morbidity may influence drug absorption, metabolization, distribution or excretion. In this paper, we will discuss the choice of a specific treatment for high blood pressure and hypercholesterolemia, taking into account the side effects of drugs and the specific clinical profile of the patient. We will focus on less known side effects in order to optimize individual patient care.

Antihypertensive Agents↗
PubMed2004

Recent advances in pathogenesis and management of hypereosinophilic syndromes.

Idiopathic hypereosinophilic syndrome is a largely heterogeneous disorder defined until now as persistent marked hypereosinophilia of unknown origin generally complicated by end-organ damage. Recent studies clearly indicate that many patients fulfilling the diagnostic criteria of this syndrome can now be classified as presenting one of two major disease variants: the myeloproliferative or the lymphocytic variant. Research in cellular and molecular biology has provided firm evidence for the existence of discrete hematological disorders underlying these variants, questioning the pertinence of continued reference to 'idiopathic' hypereosinophilic syndrome in such patients. Furthermore, identification of these variants has a number of prognostic and therapeutic implications that must be taken into consideration for adequate management of these patients.

Humans↗
PubMed2004

[Usual interstitial pneumonia].

We report the case of a 49-year old woman with an idiopathic pulmonary fibrosis (IPF) initially diagnosed as a systemic lupus erythematosus. The IPF is an uncommon clinical entity with an estimated prevalence from 3 to 6 cases per 100,000 in the general population of the United States. This disease is characterised by an insidious onset, a pejorative course and poor survival prognosis (median survival: 2.8 years). The diagnosis is often difficult and depends on the exclusion of other diseases associated with interstitial lung injury. It is generally established only after collegial coordination between the clinician, the radiologist and the pathologist. New consensuses are now published to establish a clear and explicit classification of the IPF. Moreover, because of the poor results obtained with conventional immunosuppressive drugs, new treatments are proposed.

Adrenal Cortex Hormones↗
PubMed2004

[Hormone therapy of ageing: myths and realities].

Is well being in the elderly be improved by hormone replacement therapy which compensate deficits accounting for generalized weakness, poor endurance, loss of muscle strength, impaired mobility and balance and decreased cognitive functions? Hormone replacement therapy of menopause has favorable effects on bone loss and decreased cognitive functions but also on several unpleasant symptoms--vasomotor instability, skin atrophy, mucosal dryness, anxiety and fatigue--but at the prize of increased incidence of cancer and cardiovascular morbidity. Decreased testosterone levels in elderly men are associated with increased fatigability, decreased muscle strength and bone mass and increased risks of accelerated atheromatosis. Testosterone substitution seems to be helpful but with side effects, particularly development of prostate cancer. Aging also affects adrenal function. The consequences of decreased DHEA production are still matter of debate. DHEA administration in elderly women seems to be associated with favorable effects on physical and psychological well being. Somatopause is characterized by a progressive decrease of growth hormone production starting as soon as the third decade. Growth hormone therapy has favorable effects on lean body mass, skin atrophy as well on body fat reduction. However, numerous side effects and the theoretical increased risk of cancer limit the use of growth hormone therapy in the elderly.

Adrenal Glands↗
PubMed2002

[Chronic fatigue syndrome: the point of view of the internist].

Chronic fatigue is a very common symptom in primary care medicine. Psychiatric causes represent more than 80% of the cases. After excluding all known causes of fatigue, 30% of the patients remain without a specific diagnosis and suffered from idiopathic chronic fatigue. The chronic fatigue syndrome (CFS) which represents a very small subset of these patients is a heterogeneous disorder characterized by fatigue, neuropsychiatric symptoms, and various other somatic complaints. The cause remains underdetermined and most of the treatments are ineffective. Antidepressants drugs may be helpful. A supportive approach, cognitive behavioural therapy and graded exercise seem so far the only evidence-based therapeutic approach.

Diagnosis, Differential↗
PubMed2002

[The general internal medicine department].

The Department of General Internal Medicine is devoted to the evaluation of patients with autoimmune systemic diseases, multiorganic disorders or presenting non specific symptoms such as chronic fatigue, unexplained weight loss or fever of unknown origin. The interest in salt and water metabolisms had led to original contributions in the treatment of hyponatremia in man and to the understanding of the osmotic demyelinating syndrome in a rat model of hyponatremia. The study of ageing in man and rodents had contributed to better understand lymphocyte and thyroid function in the elderly. The care for patients with various autoimmune disorders led to original observations in the pathogenicity of Sjögren's syndrome adult onset Still disease or sarcoidosis as well as the follow up of patients treated with azathioprine. Intensive collaboration with the Department of Immunology led to identify Th2 clonal lymphocytes as the cause of the so-called idiopathic hypereosinophilic syndrome in some patients and to define the clinical and biological features in this subset of patients.

Belgium↗
PubMed2001

Clonal Th2 cells associated with chronic hypereosinophilia: TARC-induced CCR4 down-regulation in vivo.

We analyzed the expression of chemokine receptors on clonal Th2-type CD4(+)CD3(- )lymphocytes isolated from blood of two patients with chronic hypereosinophilia. First, we observed that these Th2 cells express membrane CCR5 and CXCR4 but neither CCR3 nor CCR4 when analyzed immediately after purification. However, CCR4 appeared following culture in human serum-free medium, suggesting that it was down-regulated in vivo. Indeed, patient's serum, but not control human serum, strongly down-regulated CCR4 expression on cultured Th2 cells. As high levels of TARC, a CCR4 ligand, were detected in the serum of four hypereosinophilic patients with CD3(-)CD4(+) clonal Th2 cells, we evaluated the effect of TARC neutralization in this system. Addition of a neutralizing anti-TARC mAb inhibited CCR4 down-regulation by patient's serum, indicating that circulating TARC contributed to CCR4 down-regulation on Th2 cells in vivo. Clonal Th2 cells did not secrete high levels of TARC themselves but induced a sustained production of TARC by monocyte-derived dendritic cells, a phenomenon that was inhibited by addition of blocking mAb against IL-4 receptor. We conclude that high circulating levels of TARC in serum of patients with chronic hypereosinophilia, most likely derived from antigen-presenting cells stimulated by Th2-type cytokines, induce down-regulation of CCR4 on Th2 cells in vivo.

Adult↗
PubMed2001

Abnormal distribution of aquaporin-5 water channel protein in salivary glands from Sjögren's syndrome patients.

Patients with Sjögren's syndrome (SS) suffer from deficient secretion of saliva due to an autoimmune destruction of salivary glands, however, glandular dysfunction also occurs without destruction. Based upon its abnormal distribution in SS salivary glands, a potential role for the water channel protein aquaporin-5 (AQP5) is proposed in the pathogenesis of SS. The immunohistochemical distribution of AQP5 was compared in minor salivary gland biopsies obtained from women after informed consent: primary SS (53.2 +/- 14 years old, n = 10), healthy volunteers (46.2 +/- 17 years old, n = 10), patients with sarcoidosis (37 and 48 years old), and patients with non-specific sialoadenitis (54 and 61 years old). Biopsies from normal subjects revealed AQP5 primarily at the apical membrane of the salivary gland acinus. In contrast, biopsies from SS patients revealed AQP5 primarily at the basal membranes of the acinus. The AQP5 distribution in biopsies from patients with other dry mouth disorders, such as non-specific sialoadenitis or sarcoidosis, was similar to biopsies from control subjects. Computer-assisted microscopy was performed to quantitatively evaluate AQP5 distribution in the immunoreactive acini of both SS and control subjects. Biopsies from SS patients had higher labeling indices (percentage of acinus area immunoreactive for AQP5) at the basal membrane when compared with biopsies from control subjects. In contrast, biopsies of SS patients exhibited lower labeling indices at the apical membrane when compared with biopsies from control subjects. To verify the specificity of the AQP5 antibody, Western blot analysis was performed on membranes from Xenopus oocytes injected with AQP5 cRNA or on membranes from minor salivary glands of control subjects and SS patients. In each case, the immunoblots had a 27 kd band, corresponding to the expected molecular weight of AQP5. Abnormal distribution of AQP5 in salivary gland acini is likely to contribute to the deficiency of fluid secretion, which is a defining feature of Sjögren's syndrome.

Adult↗
PubMed2001

[DHEA: orthodox or alternative medicine?].

The exact physiological role of DHEA remains unknown but DHEA supplementation has recently been proven beneficial in typical deficient states like adrenal insufficiency or major depressive illlnesses. The putative favorable effects of DHEA in other conditions remain controversial. However, recent studies confirmed positive effects of DHEA administration in healthy elderly people, mostly more than 70 years old women, on skin, bone density, muscle strength and several neuropsychological symptoms. Positive effects on sexual interest and satisfaction and sense of well-being are more consistent in elderly women than in men. The recommended administered dose is 25 mg to 50 mg once a day in women and 100 mg in men. Androgenic side effects (greasy skin, acne, increased growth of body hair) are frequent but reversible side effects. Dose adaptation is recommended in these conditions. It is justifiable to prescribe DHEA in patients with adrenal insufficiency. Other possible indications are depression and prolonged glucocorticoid therapy. In elderly people, DHEA administration might be considered in DHEA depleted-patients with skin dryness or atrophy, muscle weakness, low bone density or neuropsychological symptoms. The treatment should be taken under close medical supervision in order to detect a possible hormone-dependent cancer such as breast cancer in women and prostatic cancer in men. The patients should be informed on the potential risks of DHEA administration and on the lack of definitive proven beneficial effects of DHEA, waiting the results of well-conducted controlled double blind prospective studies.

Adjuvants, Immunologic↗
PubMed2000

Interferon alpha prevents spontaneous apoptosis of clonal Th2 cells associated with chronic hypereosinophilia.

A recent study identified a clonal expansion of CD3(-)CD4(+)cells secreting Th2-type cytokines in 4 patients with chronic hypereosinophilia. Because interferon alpha (IFN-alpha) is used in the therapy of the idiopathic hypereosinophilic syndrome, the effects of this cytokine on the survival of clonal Th2 cells isolated from the blood of 2 patients were determined. First, these cells displayed a high rate of spontaneous apoptosis on culture in cytokine-free medium and were also sensitive to Fas-mediated apoptosis induced by soluble Fas ligand. Addition of IFN-alpha or interleukin-2 (IL-2) to culture medium resulted in significant protection against spontaneous but not Fas-induced apoptosis. Although spontaneous apoptosis of the clonal Th2 cells was clearly associated with down-regulation of both bcl-2 and bcl-x(L) levels, IFN-alpha had no significant effect on the expression of these antiapoptotic proteins, whereas addition of IL-2 resulted in higher levels of bcl-2. On the other hand, IFN-alpha decreased the numbers of cells with disrupted mitochondrial transmembrane potential both during spontaneous apoptosis and after exposure to protoporphyrin IX. Thus, IFN-alpha might promote the survival of clonal Th2 cells, an effect that could be relevant to the therapeutic approach for patients with chronic hypereosinophilia caused by clonal expansion of Th2-type cells. (Blood. 2000;96:4285-4292)

Adult↗
PubMed2000

[Chronic hypereosinophilia: a model of Th2 disorders].

Interleukin-5 produced by Th2-type lymphocytes is involved in the pathogenesis of a number of hypereosinophilic disorders. We and others have identified clonal Th2 cells with abnormal surface phenotypes in peripheral blood of certain patients presenting the idiopathic hypereosinophilic syndrome. We took advantage of the CD3- CD4+ phenotype of our patients' T cells to determine the activation signals involved in their production of Th2 cytokines and expansion, independently of T cell receptor engagement. In vitro cocultures performed with dendritic cells demonstrated the critical role of co-stimulatory signalling through B.7/CD28 and LFA-3/CD2 pathways and the involvement of an autocrine IL2/IL2R loop in the activation of these Th2-type cells. The high-level spontaneous apoptosis displayed by these cells in vitro was drastically inhibited by IL2 and IFN-alpha. New therapeutic strategies could result from our observations. Indeed, the hypereosinophilic syndrome may represent an unexpected application of new immunomodulatory molecules such as CTLA4-Ig and anti-IL2R-alpha.

Apoptosis↗
PubMed2000

Clonal Th2 lymphocytes in patients with the idiopathic hypereosinophilic syndrome.

Idiopathic hypereosinophilic syndrome (HES) and Gleich's syndrome are related disorders characterized by persistent or recurrent hypereosinophilia of unknown origin. Elevated IgE levels and polyclonal hypergammaglobulinaemia are considered as markers of benign outcome in this setting as they are generally associated with predominant cutaneous manifestations and favourable response to glucocorticoid therapy. In a previous study, we identified a clonal population of CD3-CD4+ Th2-like lymphocytes secreting interleukin (IL)-5 and IL-4 in peripheral blood of a patient fulfilling the diagnostic criteria of HES with associated serum hyper-IgE. We now extend this observation by describing identical findings in three additional patients, and we compare their clinical and biological parameters with five other patients with HES. Chromosomal abnormalities were detected in purified CD3-CD4+ Th2 cells from three patients, among whom one developed anaplastic null cell lymphoma. We therefore suggest that a careful search for T-lymphocyte clonality and cytogenetic changes should be included in the work-up of HES for adequate management.

Adult↗
PubMed2000

[The generalist and immunosuppressive agents].

The general practioneer is frequently concerned by the follow-up of patients receiving immunosuppressive agents for auto-immune diseases or for the prevention of graft rejection. We here review the side effects of the most frequently used immunosuppressive drugs: glucocorticoids, azathioprine, cyclophophamide, cyclosporine and methotrexate. Important drug interactions are also mentioned. We also discuss the adult vaccine schedule for patients treated with immunosuppressive agents. Finally, the consequences of immunosuppressive drugs on fertility and pregnancy are developed.

Adult↗
PubMed2000

[Clinical approach to inflammatory syndromes in the aged].

Primary care physicians have often to provide care to elderly patients presenting with non specific general complaints such as anorexia, weight loss and fatigue associated with biological inflammatory tests (increased erythrocyte sedimentation rate, increased CRP, anemia of inflammatory origin). In elderly patients, inflammatory diseases of unknown origin are most often related to an infectious illness (particularly bacterial endocarditis or tuberculosis), a systemic autoimmune disorder (temporal arteritis, polymyalgia rheumatica or ANCA positive vasculitis) or a neoplastic process. A methodological clinical approach is discussed and the most valuable complementary tests are proposed.

Aged↗
PubMed1999

T-cell receptor-independent activation of clonal Th2 cells associated with chronic hypereosinophilia.

We recently observed a clonal expansion of CD3(-)CD4(+) T cells secreting Th2-type cytokines in patients presenting chronic hypereosinophilia. As clonal T cells isolated from such patients did not spontaneously secrete cytokines in vitro, we reasoned that costimulatory signals delivered by antigen-presenting cells might be required to induce their full activation. To address this question, we investigated in two such patients the responses of CD3(-)CD4(+) T cells to dendritic cells (DC). DC elicited proliferation and production of interleukin-5 (IL-5) and IL-13 by clonal cells from patient 1 and upregulated their expression of CD25 (IL-2R-alpha). These effects were abolished when blocking monoclonal antibodies (MoAbs) against IL-2R-alpha and IL-2 were added to cocultures, indicating critical involvement of an autocrine IL-2/IL-2R pathway. Cells from patient 2 were stimulated by DC to produce Th2 cytokines only when rIL-2 or rIL-15 was added to cocultures. In both patients, addition of inhibitory MoAbs against B7-1/B7-2 or CD2 to cocultures resulted in dramatic reduction of cytokine production and inhibited CD25 upregulation. Thus, TCR/CD3-independent activation of clonal Th2 cells by DC is an IL-2-dependent process, which requires signaling through CD2 and CD28.

Adult↗