Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Antimalarials are beneficial therapeutic agents in systemic lupus and rheumatoid arthritis. These autoimmune diseases have abnormally low apoptosis of inflammatory cells. Both disorders have an abnormal angiogenesis. In the present report, antimalarials were demonstrated to selectively increase apoptosis of HUVECs in vitro. A 24-h exposure to 50 or 150 microM of the drugs was associated with a significant loss of substrate-adherent cells. Chloroquine exhibited an inhibitory effect on HUVEC proliferation over 7 days. Programmed cell death in HUVECs rendered nonadherent by chloroquine was confirmed by the induction of DNA fragmentation in floating cells. Northern blot analysis revealed a rapidly increased expression of the bcl-x(s) gene without any change in the expression of the bcl-2 gene, indicating that HUVECs under chloroquine were undergoing apoptosis. The onset of the apoptotic cascade in HUVECs appeared shortly after the addition of chloroquine. The effect of chloroquine on apoptosis was distinct from acute cell lysis and was restricted to HUVECs. Antimalarials also induced IL-1alpha production. In parallel, chloroquine alone did not increase the expression of IL-6. Anti-IL-1alpha Ab or IL-1Ra only marginally reversed chloroquine-induced depression of proliferation for the low drug concentration, but not the massive cell death effect at and above 50 microM. Taken together, these data may indicate that antimalarials repress angiogenesis. The autocrine mechanism involving IL-1alpha accounts only for a minor fraction of the full antiendothelial effect of chloroquine, which is mainly dependent on apoptosis.
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PMID:Mechanisms of action of antimalarials in inflammation: induction of apoptosis in human endothelial cells. 902 28

Intractable headaches, the so-called 'lupus headaches', have been long thought of as a common and characteristic manifestation of systemic lupus erythematosus (SLE). Seventy-eight patients with SLE, including 10 patients with definite central nervous system (CNS) involvement, and 89 healthy individuals matched for age, sex and socioeconomic status, were studied by a specific questionnaire addressing the characteristics and type of headache. Clinical features of SLE, neurological manifestations and treatment, disease severity and autoantibody profiles were correlated to the presence of headache. One year prevalence of headache was similar between patients (32%) and otherwise healthy individuals (30%). No significant differences regarding frequency, family history of headache and need for analgesic medication were observed. Headache refractory to analgesic treatment, but responsive to corticosteroid regimen, was recorded in only one patient. Clinical and serological features of SLE, including Raynaud's phenomenon and the presence of anticardiolipin antibodies, were not significantly different between headache sufferers and non-sufferers. In the majority of patients reporting headache, anxiety and/or depression co-existed. Episodic tension headache was the most frequent type, while migraine was traced in a quarter of headache sufferers. Neither the presence nor the clinical type of headache was related to, or predictive of, the development of seizures or psychosis. These results indicate that headache is not specifically related to SLE expression or severity, and suggest that accepting the presence even of a severe headache as a neurological manifestation of SLE in the absence of seizures or overt psychosis may result in overestimation of the disease status.
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PMID:Headache in systemic lupus erythematosus: a controlled study. 956 71

Thrombosis, thrombocytopenia, recurrent fetal loss and a variety of non-thrombotic neurological disorders have all been associated with antiphospholipid antibodies (aPL). Cerebral ischemia associated with aPL is the most common arterial thrombotic manifestation. Depression, cognitive dysfunction, depression and psychosis have all been associated with aPL. The presumed pathophysiologic mechanism underlying these manifestations is thought to be a result of cerebral ischemia in some, but not all cases. Seizures, chorea and transverse myelitis all appear to be associated with aPL. An interaction between aPL and central nervous system cellular elements rather than aPL-associated thrombosis seems to be a more plausible mechanism for these clinical manifestations. Migraine on the other hand, does not appear to be associated with aPL in either lupus or non-lupus populations. Neuroimaging studies show an increased frequency of brain abnormalities in patients with aPL, but none appear to be specific. The best treatment strategy for preventing neurological manifestations of aPL is not fully defined. For thrombotic manifestations, both antiplatelet and anticoagulant therapies have been suggested. In some patients, immunosuppressant therapy has been used. For non-thrombotic manifestations, some combination of immunosuppressant therapy and symptomatic treatment may be warranted.
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PMID:Neurological manifestations of antiphospholipid antibody syndrome. 981 77

This paper summarizes results from genetic studies of Nordic carnivore populations bred in captivity. The conservation genetic implications of those results for the management of wild populations of the same species are discussed. Inbreeding depression has been documented in the brown bear (Ursus arctos), wolf (Canis lupus), and lynx (Lynx lynx) populations held in Nordic zoos. The characters negatively affected by inbreeding include litter size (brown bear and wolf), longevity (lynx and wolf), female reproduction, and weight (wolf). In addition, hereditary defects caused by single autosomal alleles occur in the wolf and brown bear populations. These deleterious alleles cause blindness (wolf) and albinism (brown bear) in the homozygous state. The amount of inbreeding depression observed in Nordic carnivores are similar to that documented in other species. The captive populations have the same genetic background as the current wild ones and inbreeding depression is therefore a potential threat to wild carnivore populations in Sweden. This threat is presently not being adequately recognized in the management of these species. Frequently occurring misunderstandings regarding the kind of conclusions that can be drawn from the presented genetic observations are also discussed.
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PMID:Conservation genetics of Nordic carnivores: lessons from zoos. 1050 37

Although lupus cardiomyopathy is thought to be clinically uncommon, we encountered 6 patients with systemic lupus erythematosus (SLE) over a 10 year period who had severe left ventricular dysfunction and showed remarkable improvement in their cardiac function after cytotoxic therapy. All patients met the American College of Rheumatology criteria for classification of SLE and presented with signs of severe biventricular failure relatively early in their disease. Concurrent manifestations of SLE at the time of cardiomyopathy included rash, arthritis, myalgias, pleuritis, pericarditis, and nephritis. Four of the 6 patients were taking prednisone 20 mg/day at the time heart failure developed. In all cases the CPK were normal. Evaluation of cardiac function by echocardiogram and/or radionuclide gated blood pool scintigraphy revealed a severe depression of ventricular function with initial left ventricular ejection fraction (LVEF) ranging from 11 to 34% (mean 19%). Within 6 months of initiation of cytotoxic treatment all patients showed a dramatic response: the post-treatment LVEF ranged from 25 to 55%. This series of patients suggests that cardiomyopathy may be a more common complication of SLE than previously reported. Cardiomyopathy occurs relatively early in the course of SLE, may lead to severe cardiac dysfunction despite corticosteroid therapy, and appears to be responsive to cytotoxic therapy.
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PMID:Dramatic improvement of left ventricular function after cytotoxic therapy in lupus patients with acute cardiomyopathy: report of 6 cases. 1052 51

The SLE database at the Rheumatology Clinic, St. Luke's Hospital currently includes 62 patients. The presentation, clinical features, ACR criteria and laboratory findings in RNP positive lupus patients [14] were compared to RNP negative subgroup [33]. RNP positivity was significantly associated with Raynaud's phenomenon (p < 0.01), myalgia (p < 0.02), myositis (p < 0.05), neuropsychiatric features (p < 0.05) and Sm positivity (p < 0.01). RNP positive patients had a higher frequency of positive family history, mortality, malar and maculopapular rashes, nail-fold infarcts, telangiectasia, digital vasculitis, photo-sensitivity, arthritis, pleurisy, pericarditis, pericardial effusions, depression, headache, psychosis and TIA.
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PMID:RNP positivity in Maltese SLE patients. 1059 38

The objectives were to determine causes of consultation, hospitalization and outcome in a cohort of lupus patients in an emergency unit. Patients with systemic lupus erythematosus (SLE) who visited the emergency department for consultation from 1 September 1996 to 17 May 1997 were included in the study. They were evaluated during the visit by looking at 100 variables such as demographic, socioeconomic, clinical, therapeutical, behavioral, (compliance), emotional (Beck depression inventory), disease activity, (Mex-SLEDAI), disease severity (Lupus SDI), chronic damage (SLICC-ACR), and physician's and patient's global assessments of severity. All causes of consultation, hospitalization and outcome were registered. Descriptive statistics, univariate analysis and multiple logistic regression were used for analysis. Significance was set at the 0.05 level. 180 patients were included. 164 were female, mean age 31.7/11.39 y, mean Mex SLEDAI score 3.8, mean SLICC-ACR 1.3. Fever, poliarthralgia and abdominal pain were the main causes of consultation with 26, 25 and 18 cases each. 49 patients were hospitalized and these were statistically different than non-hospitalized patients in level of formal education (10.2 vs 11.8, P=0.03); compliance (7.6 vs 9, P=0.0001); malar rash (57% vs 82%, OR, 95% CI=0.28, 0.13-0.62, P=0.0008), chloroquine daily dose intake (45 vs 77 mg, P=0.04); disease severity in physician's global assessments (5.6 vs 2.1, P=0.0001) and Beck depression inventory (21 vs 16, P=0.01). Multiple logistic regression identified physician's global assessment, fewer ACR criteria and higher SLICC-ACR scores as the main variables associated with hospitalization. Five patients died; two with community acquired pneumonia, one with pancreatitis, multiple thromboses, and sepsis, one with pulmonary hemorrhage; and one with pulmonary thromboembolism. In conclusion, poor compliance, low level of formal education, severity, depression, lower ACR criteria and higher SLICC-ACR scores were important variables identified with hospitalization. Chloroquine use seemed to have a protective effect. Causes of death were related to infections and antiphospholipid syndrome.
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PMID:Lupus patients in an emergency unit. Causes of consultation, hospitalization and outcome. A cohort study. 1103 35

Lupus profundus is an unusual clinical variant of cutaneous lupus erythematosus that has previously been described as a benign disease that follows a mild course. This report describes the extent of disease and associated comorbidities in patients with severe lupus profundus and systemic lupus erythematosus. Four cases of lupus profundus are reviewed and their associated systemic disease complications are highlighted. All four patients fulfilled at least four of the 11 criteria for systemic lupus erythematosus. One patient suffered from severe facial disfigurement and Parry-Romberg syndrome. Two patients developed nonhealing ulcers on the scalp. All four patients had scarring alopecia as well as depressed areas over large areas of their body surfaces. All patients were resistant to conservative therapy, and required long-term aggressive therapy. Clinical depression secondary to disfigurement was a major problem in three patients. Extensive lupus profundus may be associated with more serious systemic disease and warrants aggressive treatment early on to prevent permanent disfigurement and its resultant psychological consequences.
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PMID:Lupus profundus: not a benign disease. 1148 Aug 52

The Psychiatry department of the University Hospital Centre of Lille has developed, over the last 10 years, a treatment network for psychiatric disorders during pregnancy or in the post-partum period. There are liaison consultations in the maternity department, screening and management of psychopathological disorders in the perinatal period, training of midwives, support of patients seeking genetic counselling, collaboration with teams providing "medically-assisted procreation", etc. For severe disorders of the post-partum period (severe depression, serious alteration of mother-child interaction, puerperal psychosis), the Psychiatry department has a specialized unit where 3 "mother-child" groups can be admitted. This unit is particularly effective if the patients and their family understand this healthcare system and stick to it to a certain extent. Even if improvements are always possible, cases in which situations occur as an emergency, are when dysfunctions are most frequently seen. On 7th December 1998, a Crisis Intervention Unit (CIU) was created with 15 short-term beds, for stays up to 72 hours. The CIU was opened in the Psychiatry department, close to the main Accident and Emergency department, with 2 aims: firstly to provide a setting and resources for a number of emergency psychiatric situations, and secondly to provide a place and time for crisis situations which we admit to the unit, with a view to facilitating interaction and to propose in certain cases a process of crisis intervention, which later continues on an outpatient basis. After being open for a year, the CIU has proved to be an improvement to all of the healthcare services which are available. It should be noted that the situations which need highly specialized resources in such a short time, are those which cause the most acute problems. This is at times when the emergency services network, with its internal logic, require another network based on a different logic, that the interface problems are at their most acute. The situations reported here, which require a fluid interface between the emergency services and the "mother-child" networks, are examples. We report 3 clinical situations, which illustrate 3 possibilities of action: the first, in which 2 successive stays in the CIU allowed an admission to the "mother-child" unit in satisfactory conditions, the second, in which overall management was based on hospitalization in the Obstetrics department and several visits to our Unit, and the last one, in which the whole medico-psycho-social approach was set up after a single stay of 3 days. Since the opening of Crisis Intervention Unit, around 1,000 patients have been treated there; 37 were women with difficulties with their pregnancy, 17 of whom required direct intervention by the "mother-child" team. The contexts were: 5 prenatal depressions, 4 post-partum depressions, 3 cases of hyperemesis gravidarum, 5 rejections of pregnancy and/or situations at risk of infanticide. The almost constant suicidal risk should be noted, or even attempted suicide, at the time of admission to the CIU. The other 20 women had psychopathological disorders linked to sterility, medically-assisted pregnancy, termination of pregnancy or pregnancy in women suffering from long-term somatic illnesses (insulin-dependent diabetes, lupus, etc.). When a psychopathological episode occurs during pregnancy, it is essential to preserve the developing relationship with the child in an intermediate place, in a healthcare perspective and to prevent any future impairment of the quality of the mother-child relationship by the psychiatric disorder. The Crisis Intervention Unit is not an emergency "mother-child" unit. Other French experiences have been reported, an example being mother-baby hospitalization in a crisis centre. The aim of our interventions is not the same, and our local context, together with the availability of a healthcare network on different floors, which is specific and close-by, allows this approach. Also, the contribution of Liaison Psychiatry in emergency situations should not be minimized. It is necessary to work in collaboration with the obstetricians. In fact, the chance to work with us was given by asking for a hospitalization in the Obstetric unit, during the prepartum period of pregnancies with a psychiatric risk. This way of proceeding allows somatic monitoring in hospital to be performed, whenever the risk run by the mother and/or the child requires it. This "analogue" procedure, however preventative it may be, does not always allow specific treatment of the psychiatric disorders to be given, despite liaison psychiatry interventions. Our interventions are not a specialized "mother-child" unit, or a substitute for Liaison Psychiatry, but they are specifically aimed at the context of the crisis. Obviously, it is precisely this dimension of the crisis which makes the other types of management temporarily unsuitable. This new working framework, with the simple possibility of admitting women and interacting with them in a crisis situation, with the aid of the competence of "mother-child" teams, most often seems to allow an alternative to hospitalization in the Psychiatry department, at the same time keeping up quality management of problems linked to the pregnancy or post-partum period. The specificity of the CIU, with its project of taking the special psychiatric vulnerability of pregnancy into account, makes sure that the psychopathological aspects of the crisis situation and the physiological aspects of adaptation reactions to the perinatal period are not neglected, but that are respected by this type of interaction/intervention.
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PMID:[Value of a consultation center and crisis intervention in addressing psychiatric disorders in the perinatal period]. 1196 46

We present two Japanese cases of involutional lipoatrophy. The first case is that of a 30-year-old woman, who first appeared at our hospital complaining of a localized, well-demarcated depression, approximately 3 x 4 cm in size, normal to slightly erythematous in coloration, on the lateral side of the left upper arm (Fig. 1a). The condition was asymptomatic, and she had noticed this anomaly a month prior to consultation. She received intramuscular injections of corticosteroids of unknown dosage at the affected site for the treatment of allergic rhinitis 4 months prior to her present consultation. The second patient, a 23-year-old woman, appeared at our hospital complaining of a similar macule 4 x 4 cm in size, which she noticed several weeks prior to her most recent consultation. She had no history of injury or injection at the site before the development of the condition (Fig. 1b). She had been under treatment for atopic dermatitis since early childhood and was treated only with topical applications of white petrolatum containing 2% salicylic acid for the past several years. In order to rule out the possibility of acquired partial lipodystrophy associated with localized scleroderma, lupus profundus and the other connective tissue diseases, a histological examination was performed for both patients. Histopathological analysis of the region exhibited a well-defined fat lobule composed of numerous small adipocytes (Fig. 1c) embedded in hyaline connective tissue. Edema and dilated capillaries were noticeable in the subcutaneous tissue surrounding the area. Inflammatory cells were not prominent, although mononuclear cells were observed in both patients. No epidermal change was seen in either patient. Direct and indirect immunofluorescence studies revealed no deposits of immunoreactants in the skin of either patient. Immunohistochemical studies with the antibody against macrophage (anti-CD68 antigen; DAKO.) showed that positive cells were scattered around blood vessels and shrunken lipocytes in the subcutaneous tissues (Fig. 1d). Most of these cells in the fat lobules were also positive for mucin stains such as Alcian blue. No abnormal findings came to light in the ordinary hematological and blood chemistry examinations of both patients. The autoantibody screening tests using antinuclear, anti-DNA, anticentromere, and anti-Scl-70 antibodies were negative in both patients.
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PMID:Two Japanese cases of localized involutional lipoatrophy. 1201 Mar 46


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