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Biomedical subjects

N Just

Publications and source records attributed to N Just.

At least 19 recordsLinked to original sources

High erythropoietin and low vascular endothelial growth factor levels in cerebrospinal fluid from hypoxemic ALS patients suggest an abnormal response to hypoxia.

Animal studies have highlighted the potentially neuroprotective role of vascular endothelial growth factor (VEGF). Low levels of this growth factor have been found in the cerebrospinal fluid (CSF) of patients with amyotrophic lateral sclerosis (ALS). VEGF (and other proteins, such as erythropoietin (EPO)) are produced in response to hypoxia via a common pathway involving a specific transcription factor (hypoxia-inducible factor, HIF) and a hypoxia responsive element (HRE) in the respective genes' promoter regions. In this study, we report finding the expected, high levels of VEGF and EPO in CSF from hypoxemic neurological controls, whereas EPO (but not VEGF) levels are high in the CSF from hypoxemic ALS patients. Hence, the VEGF levels in CSF from patients with ALS were significantly lower than those seen in hypoxemic controls. There was a trend towards higher CSF levels of EPO in hypoxemic ALS patients than in hypoxemic controls. Our results suggest that VEGF may not be produced in sufficient amounts in chronically hypoxic ALS patients and that this dysfunction may participate in the pathogenesis of the disease. The high EPO levels in hypoxemic ALS patients nevertheless suggest an intact common oxygen-sensor pathway.

Adult↗

Paradoxical response of VEGF expression to hypoxia in CSF of patients with ALS.

Vascular endothelial growth factor (VEGF) is implicated in motor neurone degeneration. In normal individuals, hypoxia is known to induce an overexpression of VEGF, as measured in CSF. We show that patients with ALS do not manifest this VEGF overexpression in the presence of hypoxia. Although VEGF gene expression is mainly stimulated by hypoxia, we have measured lower VEGF levels in cerebrospinal fluid (CSF) from hypoxaemic patients with amyotrophic lateral sclerosis (ALS) than in CSF from normoxaemic patients with ALS. In contrast, hypoxaemic neurological controls displayed higher levels than normoxaemic neurological controls. There was a negative correlation between VEGF levels and the severity of hypoxaemia in patients with ALS, suggesting deregulation of VEGF in ALS.

Adult↗

Elevated IL-6 and TNF-alpha levels in patients with ALS: inflammation or hypoxia?

Abnormal levels of interleukin (IL)-6 were described in patients with ALS, related to an inflammatory process. The authors compared IL-6 and tumor necrosis factor alpha (TNF-alpha) levels in CSF and sera from 10 hypoxemics and 10 normoxemics patients with ALS to those of 10 hypoxemics and 10 normoxemics neurologic controls. The same pattern exists in patients with ALS and controls: the highest levels are found in hypoxic conditions and undetectable levels are found in normoxemic conditions. Elevated IL-6 levels in ALS could correspond to a normal response to hypoxemia.

Aged↗

[Immediate allergy to oral corticosteroids].

INTRODUCTION: Corticosteroids are widely used for the management of many diseases because of anti-inflammatory and immunomodulatory properties. Sulfite intolerance is well known but immediate hypersensitivity to corticosteroids is rarer and must be reported. EXEGESIS: We report a case of a 38-year-old man, followed since 1986 for asthma with sulfite intolerance. He twice developed urticaria after ingesting betalactam antibiotics associated with corticosteroids of the group A, according to the Matura and Goossens's classification. The allergy inquiry confirmed not only a beta-lactame allergy but also in corticosteroids of the group A. Intradermal reactions with methylprednisolone and hydrocortisone were positive at 7 mm for methylprednisolone on 1/1000 dilution and at 4 mm for hydrocortisone on 1/10 dilution. Thus immediate allergy to corticosteroids was confirmed. But those skin tests were negative for corticosteroids of group B and C. In order to propose an alternative therapy for acute asthma, an intravenous injection of 4 mg of betamethasone was performed without inducing immediate and delayed allergic reactions. CONCLUSION: Corticosteroid allergy is rare and can be fatal. Many asthmatic or acetylsalicylic acid intolerant patients may be concerned. The diagnostic of corticosteroid allergy have to be confirmed by clinical history and skin tests of the different groups to try to identify one or more allergens and to propose a alternative treatment if necessary.

Administration, Oral↗

[Management and treatment of respiratory failure associated with amyotrophic lateral sclerosis].

INTRODUCTION: In amyotrophic lateral sclerosis (ALS), respiratory muscle involvement is highly predictive of survival and quality of life (QOL). There is compelling evidence that non invasive ventilation (NIV) prolongs survival by several months and improves QOL more than any other currently available treatment. Frequent testing of pulmonary function and regular evaluations are recommended since 1999 by the American Academy of Neurology in order to take appropriate treatment decisions. STATE OF ART: There are numerous tests available to evaluate respiratory status in ALS and it is important to know their sensitivity and specificity to recognize clinical risk situations. Some recent data suggest that sniff nasal pressure and maximal inspiratory pressure (MIP) can be performed reliably by most ALS patients and are more sensitive to decrements in inspiratory muscle strength than spirometry or arterial blood gasometry. PERSPECTIVES: Airway obstruction caused by ineffective coughing is the principal cause of intolerance to NIV. Several factors other than respiratory muscle strength may affect pulmonary function: postural changes, nutritional status, infectious disease, drugs. CONCLUSION: The neurologist has to coordinate multidisciplinary care, with attention to individual patient preferences, and with a frank and compassionate discussion between the patient, the family, the physicians and the caregivers.

Amyotrophic Lateral Sclerosis↗

Low levels of the vascular endothelial growth factor in CSF from early ALS patients.

Deletion of the hypoxia-response element in the vascular endothelial growth factor (VEGF) promoter causes motor neuron degeneration in a mouse model. "At-risk" haplotypes with low circulating VEGF levels have been demonstrated in humans. Here the authors report low VEGF levels in the CSF of ALS patients during their first year of the disease, independently of VEGF promoter polymorphism. This finding early in ALS patients suggests a possible role for VEGF gene regulation in the pathogenesis of ALS.

Aged↗

[Involvement of the nasal sinuses in sarcoidosis. A prospective study of 63 patients].

INTRODUCTION: Sarcoidosis is a diffuse granulomatous inflammatory disorder of unknown aetiology. Involvement of the nasal sinuses has been reported only rarely. METHODS: This multicentre prospective study was undertaken on patients suffering from histologically confirmed sarcoidosis between October 2001 and August 2002. It comprised a questionnaire for nasal symptoms, a nasal endoscopy and a CT scan of the nasal sinuses. RESULTS: Among the 62 patients enrolled 38 reported at least one nasal sinus symptom. An abnormality of the CT scan was present in 70% of cases. None were specific for sarcoidosis. Rhinoscopy revealed a mucosal lesion in 11 cases. The presence of mucosal nodules on the turbinates was suggestive of sarcoidosis and was proven histologically in 4 cases (6.5%). In these 4 cases there were symptoms of nasal sinus involvement and extensive CT changes. CONCLUSIONS: Involvement of the nasal sinuses is rare in the course of sarcoidosis. Anterior rhinoscopy allows diagnosis before the development of typical lesions and also the taking of guided biopsies.

Adult↗

[Involvement of dendritic cells in allergic airway diseases].

INTRODUCTION: Dendritic cells (DCs) are able to present antigen to T lymphocytes and to orientate the immune response towards a Th1 or a Th2 type. STATE OF THE ART: The aim of this report is to present different studies comparing DCs from allergic patients with those from healthy subjects using in vivo and in vitro experimental conditions. These studies have demonstrated that cellules dentritiquess from house dust mite allergic patients:i) take up house dust mite allergen more efficiently, ii) after stimulation by house dust mite allergen, secrete a restricted panel of cytokines and chemokines, and express characteristic co-stimulatory molecules, favoring a Th2 profile, iii) after stimulation by house dust mite allergen, induce Th2 cytokines secretion by T lymphocytes, and iv) favor an allergen-specific Th2 airway inflammatory response in an in vivo model of humanized mice. PERSPECTIVES: Functional modulation of DC could be a new therapeutic concept in allergic airway diseases. CONCLUSIONS: These results show phenotypic and functional specificities of DC from house dust mite allergic patients, and suggest a key-role for cellules dentritiques in the pathogenesis of allergen-dependent airway inflammatory response.

Dendritic Cells↗

[Langerhans cell histiocytosis and sclerosing cholangitis in adults].

INTRODUCTION: Langerhans cell histiocytosis and sclerosing cholangitis are two rare diseases that are frequently linked in children, but very rarely so in adults. CASE REPORT: A 40 year old woman with a 17 year history of Langerhans cell histiocytosis with chronic respiratory failure and diabetes insipidus presented with cholestatic jaundice whilst being assessed for lung transplantation. Pathological examination demonstrated sclerosing cholangitis. No Langerhans histiocytosis lesions were found in the liver or the biliary tract. Plans for pulmonary and hepatic transplantation were abandoned after cerebral involvement was detected, and the patient died of acute hepatic failure. CONCLUSION: This case underlines the need to monitor liver function in adult patients with disseminated Langerhans histiocytosis associated in adults, as coexisting sclerosing cholangitis is associated with a poor prognosis.

Adult↗

Keratinocyte growth factor (KGF) decreases ICAM-1 and VCAM-1 cell expression on bronchial epithelial cells.

Activation of leucocytes during airway inflammatory reaction involves adhesion to bronchial epithelial cells (BEC), a process implicating specific interactions between glycoproteins with epithelial cell surface proteins, mainly intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1). In this study, the effect of keratinocyte growth factor (KGF), a growth factor involved in pulmonary epithelium repair, was evaluated on adhesion molecule expression with BEAS-2B cells and BEC and granulocyte adherence to BEAS-2B. The modulation by KGF of membrane and mRNA expression of ICAM-1 and VCAM-1 was studied on confluent cells stimulated or not with tumour necrosis factor-alpha (TNF) (200 UI/ml) or TNF and interleukin (IL)-4 (50 UI/ml and 10 ng/ml). Levels of soluble-(s)ICAM-1 and sVCAM-1 were measured by ELISA. Although moderately, KGF significantly decreased membrane ICAM-1 expression in unstimulated BEAS-2B cells (24% inhibition at 100 ng/ml) or in TNF- or TNF + IL-4-stimulated cells (22.5 and 18.7% inhibition, respectively). Treatment with KGF tended to decrease VCAM-1 expression in TNF- and TNF + IL-4-stimulated BEAS-2B (P = n.s. and P < 0.05, 14 and 15% inhibition, respectively). In primary culture of BEC, adhesion molecule expression was also reduced. ICAM-1 and VCAM-1 mRNA expression were also inhibited by KGF. Levels of sICAM-1 and sVCAM-1 were not significantly increased in supernatants from KGF-treated cells (30% and 24% increase at 100 ng/ml, respectively) compared to controls. Moreover, KGF decreased by 31% the adherence of neutrophils to TNF-activated BEAS-2B. In conclusion, KGF decreases ICAM-1 and VCAM-1 expression and neutrophil adherence in BEC. These suggest its involvement in the resolution of the inflammatory reaction.

Bronchi↗

[Intra-cavity aspergilloma complicating necrotising sarcoid granulomatosis].

INTRODUCTION: Necrotising sarcoid granulomatosis is a rare clinical entity, characterised by the development of nodular pulmonary opacities, the diagnosis if which is based on the identification of characteristic pathological lesions. CASE REPORT: A 44-years-old male smoker presented with cough and fever. With the exception of a few basal crepitations clinical examination was normal. The chest x-ray showed multiple areas of alveolar consolidation scattered throughout both lung fields, some of which were cavitated. The thoracic CT scan confirmed the presence of cavitating nodules and hilar and mediastinal lymphadenopathy. Samples for mycobacteria were negative. A search for anti-neutrophil cytoplasmic antibodies was negative. Fibreoptic bronchoscopy was normal but transbronchial biopsies revealed giant cells. Lung biopsies taken by video thoracoscopy showed non-caseating granulomata with areas of fibrinoid necrosis and perivascular infiltration with lymphocytes, histology characteristic of necrotising sarcoid granulomatosis. Resolution occurred without treatment. The parenchymal lesions regressed leaving residual cavities. Four years later, following an episode of haemoptysis, the patient was found to have a squamous cell carcinoma (T1N0M0) and aspergillomas in the pulmonary cavities. CONCLUSIONS: Our observation demonstrates that the cavities of necrotising sarcoid granulomatosis may be complicated by aspergillomas.

Adult↗

[Multifocal epithelioid haemangioendothelioma: a difficult diagnosis].

INTRODUCTION: Epithelioid haemangioendothelioma is a rare vascular tumour of slow growth and unfavourable outlook, with occasional spontaneous and complete remissions. CASE REPORT: We report the case of a 69 year old woman admitted to hospital on account of haemoptysis. The clinical and radiological findings were compatible with diffuse pulmonary haemorrhage of unknown aetiology. Lung biopsy revealed a picture of pulmonary haemorrhage without vascular changes or tumour cells. Further progress was characterised by recurrent haemoptysis and the development of a haemothorax, liver nodules and skin lesions, biopsy of which confirmed the diagnosis of epithelioid haemangioendothelioma. The patient died several weeks later. CONCLUSION: The pulmonary localisation of epithelioid haemangioendothelioma is non specific, represented mainly by parenchymatous nodules with or without accompanying haemoptysis. Haemothorax is a more uncommon presentation of this disorder and a pleural localisation is often associated with a multifocal and aggressive form. The pathological diagnosis is most often made by surgical lung biopsy. Nevertheless in certain cases it can be difficult to make and this case report shows that, in the presence of a haemothorax, the search for extrapulmonary deposits accessible for biopsy may prove useful.

Aged↗

[The role of exercise testing in the management of systemic sarcoidosis].

INTRODUCTION: Patients suffering from sarcoidosis sometimes report dyspnoea of effort. The restrictive or obstructive ventilatory problems contribute to this disability, but the systemic manifestations of sarcoidosis should be considered as other possible causes of the dyspnoea. CASE REPORT: We report a case of systemic sarcoidosis in a 29 year old man from the Ivory Coast. The disorder presented in December 1999 with generalised symptoms and grade II dyspnoea (Sadoul). Investigations confirmed pulmonary, mediastinal, hepatic, lachrymal and salivary involvement. Lung function tests at rest showed a combined restrictive and obstructive ventilatory defect. The initial exercise test showed evidence of severe limitation of aerobic metabolism with impaired oxygen uptake without limitation of ventilation. The absence of cardiac involvement, confirmed by echocardiography and myocardial isotope scanning, suggested that the dyspnoea was, at least in part, secondary to a "peripheral" muscular abnormality. After 3 months treatment with oral corticosteroids, the clinical and physiological parameters improved. Exercise testing confirmed an improvement in maximum work rate and oxygen uptake. The relative stability of the functional measurements and the subsequent development of myalgia prompted a biopsy of the quadriceps that showed granulomata within the muscle tissue, confirming a sarcoid myopathy. A combination of steroids and methotrexate allowed the patient to increase his exercise capacity without any major change in the resting lung function tests. CONCLUSIONS: This case report underlines the role of exercise testing in determining the cause of dyspnoea. In this patient it contributed to the diagnosis of sarcoid myopathy and lead to modification of his treatment.

Adult↗

[A favourable outcome in yellow nail syndrome: role of respiratory physiotherapy].

INTRODUCTION: The yellow nail syndrome is a rare condition that is easily diagnosed but the nail manifestations are poorly understood. CASE REPORT: A 51 year old patient presented with a chronic cough. The diagnosis was based on the typical appearance of the nails. The patient had bilateral basal bronchiectasis. Daily physiotherapy with bronchial drainage lead to a progressive improvement in the respiratory symptoms without recourse to antibiotics. Surprisingly the abnormalities of the nails disappeared after 2 years treatment. CONCLUSION: This observation illustrates the possibility of spontaneous resolution of severe nail abnormalities during the course of the yellow nail syndrome.

Breathing Exercises↗

[Needle aspiration in paradoxical hypertrophy of tuberculous lymphadenitis].

INTRODUCTION: Paradoxical hypertrophy is frequent in case of peripheral lymph node tuberculosis. Its management remains controversial. CASE STUDY: We report a case of susclavicular and anterior cervical lymph nodes tuberculosis complicated by paradoxical hypertrophy after 4 months of treatment in a 59-year-old woman. The lymph node was not compressive but was limiting the cervical mobilisation. The caseum was sucking three times with a fine needle. Thereafter we performed an isoniazid injection each 24 hours for three days at three different lymph node sites. Antituberculous treatment was reinitiated for 10 months at all and lymph nodes completely disappeared without functional sequels. CONCLUSION: Paradoxical hypertrophy is a frequent complication of peripheral lymph node tuberculosis. Caseum suction of the paradoxical hypertrophy with a fine needle may constitute an alternative treatment of surgery.

Antitubercular Agents↗

Remitted depression studies as tests of the cognitive vulnerability hypotheses of depression onset: a critique and conceptual analysis.

Investigations of cognitive patterns among individuals who have recovered from a depressive episode (i.e., remitted depressives) have figured importantly in evaluations of the validity of the vulnerability hypotheses of the cognitive theories of depression. However, we suggest that remitted depression studies as typically conducted and interpreted are inadequate tests of the cognitive vulnerability hypotheses of depression onset for four reasons: (1) remitted depression studies are based on the erroneous assumption that cognitive vulnerability should be an immutable trait; (2) remitted depression studies use a logically "backward" participant selection strategy in which participants are selected on the basis of the "dependent" variable (depression) and then compared on the "independent" variable (cognitive vulnerability), which is likely to result in heterogeneity of cognitive vulnerability among both the remitted depressed as well as the nondepressed groups given the causal relations specified in the cognitive theories of depression; (3) many remitted depression studies have ignored the possible activating role of stress in the cognitive vulnerability-stress theories, particularly Beck's theory, and thus, may attempt to assess cognitive vulnerability at a time when it is not operative (i.e., priming hypothesis); and (4) remitted depression studies inappropriately use postmorbid participants to test causal hypotheses, and therefore, are ambiguous about whether negative cognitive styles observed in remitted depressed persons are vulnerabilities as opposed to consequences of depression (i.e., scar hypothesis). As a remedy, we advocate the use of a theory-guided behavioral high-risk strategy to more adequately test the cognitive vulnerability hypotheses of depression onset.

Cognition↗

Pain expectancy and work disability in patients with acute and chronic pain: a test of the fear avoidance hypothesis.

According to the fear avoidance model, prolonged disability among patients with chronic nonmalignant pain is due, in part, to an exaggerated fear of pain. At issue in the present study was an attempt to refine the fear-avoidance hypothesis by eliciting estimates of anticipated pain as well as anticipated injury. Along with scores on the Fear Avoidance Beliefs Questionnaire-Work (FABQ-W), a validated measure of fear avoidance, pain and injury expectancies were used as predictors of work disability in a hierarchical regression model. We also examined the possibility that fear avoidance might be confined to patients with chronic pain and thus fail to account for work impairment after the onset of acute injury or illness. Samples of patients with acute (N = 47) and chronic (N = 56) pain completed a battery of psychological tests. Pain and injury expectancies collectively explained 40% to 35% of the variance in work disability compared with 12% to 10% explained by the FABQ-W for the acute and chronic samples, respectively. After controlling for pain duration, depression, somatization, and current pain severity, pain expectancy alone accounted for 16% of the variance in patients in the chronic group (P < .001) and 33% of the variance in patients in the acute group (P < .001). Both pain and injury expectancies were associated equally with work disability for patients in the acute group (P < .001), but only pain expectancy accounted for variance in the chronic group (P < .001). Fear-avoidance beliefs, in the form of cognitive expectancies, may have as much influence on the duration of disability in patients with acute pain as they do in patients with chronic pain.

Journal Article↗