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Biomedical subjects

L Airaghi

Publications and source records attributed to L Airaghi.

At least 19 recordsLinked to original sources

Negative association between occurrence of type 1 diabetes and tuberculosis incidence at population level.

In the last decades of the 20th century, the incidence rate of type 1 diabetes increased in affluent countries. The pattern of occurrence of this autoimmune disease over time could provide helpful information to discriminate between alternative aetiologic hypotheses. In addition to genetic disposition, the incidence of type 1 diabetes seems to be conditioned by environmental factors and lifestyle. One theory proposes that the increase in the prevalence of autoimmune diseases is a result of the decrease in the incidence of childhood infections. To investigate the relationship between the incidence of type 1 diabetes and the decline of infectious diseases, we calculated the correlation between the occurrence of type 1 diabetes and tuberculosis in several European and non-European countries. The results of our analysis demonstrate an inverse correlation between the occurrences of type 1 diabetes and tuberculosis. A possible interpretation of this negative association is that a high socio-economic status and a westernised way of life imply a reduced or delayed exposure to infectious agents and so a reduced or delayed "pressure" on the immune system, which is free to mount inappropriate responses against self-antigens, as happens in type 1 diabetes.

Adolescent↗

Unusual presentation of large B cell lymphoma: a case report and review of literature.

Diffuse large B cell lymphoma (DLBCL) is the largest subtype of non-Hodgkin's lymphomas (NHLs) and is characterized by relatively frequent extranodal presentation. In these cases, the most common extranodal localizations are stomach, CNS, bone, testis and liver. Simultaneous detection of multiple extranodal involvement at presentation is quite uncommon, with the majority of these cases characterized by gastric or intestinal disease localization. Retrospective analysis concerning multifocal extranodal NHLs never pointed out disease features such as those described here. We report a patient with an unusual presentation of DLBCL, characterized by adrenal and renal involvement, associated with symptoms and signs of the cold agglutinin disease and a hypercoagulable state. Subsequently, computed tomography (CT) and fluorodeoxyglucose-positron emission tomography (FDG-PET) scanning disclosed a rapidly extensive spread to nodes and bones. Cytofluorimetric analysis of a renal specimen showed medium-to-large lympho-monocytoid elements positive for CD20 with monoclonal expression of immunoglobulin kappa light chain. Histopathological examination confirmed a renal CD20 positive DLBCL localization.

Adrenal Gland Neoplasms↗

Early peripheral nerve abnormalities in impaired glucose tolerance.

Increased prevalence of impaired glucose tolerance (IGT) has been recently detected in patients with painful sensory neuropathy. To determine whether nerve abnormalities are present in IGT we investigated IGT subjects without clinical neuropathy. Nerve conduction studies (NCS) were performed in 12 subjects with IGT without symptoms and signs of neuropathy. The results were compared with those obtained from 12 patients with type 2 diabetes (DM) without clinical neuropathy and 12 healthy controls. Sensory NCS of the sural nerve were performed on different segments, the distal-leg (10 cm proximal to the lateral malleolus) and the proximal-leg segment (10 cm more proximal). The distal conduction velocity of the sural nerve was increased in IGT subjects, compared both to healthy controls and DM patients. No difference was found among the groups with respect to the sensory conduction velocity of the sural nerve fibers in the proximal-leg segment. A reduction of both distal and proximal amplitudes of the sural nerve action potentials was detected in DM patients compared with IGT subjects and controls. The abnormal conduction velocity in the distal segment of the sural nerve, observed in IGT subjects without clinical neuropathy, suggests that the myelin dysfunction of the distal sensory fibers represents the earliest detectable nerve response to the hyperglycemia. The reduced amplitude of the sural nerve action potential in asymptomatic patients with DM arises from the axonal degeneration and represents a more advanced stage of nerve disease.

Diabetic Neuropathies↗

Duodenal ulcers preceding cervical tuberculous lymphadenitis.

Lymphadenitis is the most common presentation of extra pulmonary tuberculosis, whereas gastrointestinal localization, particularly duodenal involvement, is rare. We report a case of extra pulmonary tuberculosis with association between cervical lymphadenitis and duodenitis with multiple ulcers, not responsive to treatment with protonic pump inhibitors, in a human immunodeficiency virus-seronegative adult woman of Eritrean origin. Clinical patterns of duodenal TB, diagnostic difficulties and aetiopathogenesis are discussed according to the literature. In this case report it is suggested that tuberculous infection must be considered when duodenal ulcers fail to respond to proton pump inhibitors, especially when the patient comes from an endemic area.

Duodenal Ulcer↗

High-dose intravenous immunoglobulin in the treatment of acute myocarditis. A case report and review of the literature.

A few reports have suggested the beneficial effect of high-dose intravenous immunoglobulin (IVIG) in the treatment of acute myocarditis and cardiomyopathy. We describe a 49-year-old woman in which acute myocarditis was diagnosed on the basis of clinical and echocardiographic findings. Conventional treatment with captopril and frusemide was administered: intravenous heparin and, subsequently, oral anticoagulants were added because of the appearance of an apical thrombus. On the fifth day of hospitalization, treatment with high-dose (400 mg kg(-1) day(-1)) IVIG was started and prosecuted for 5 days. A dramatic improvement of clinical conditions was observed, with increase of the left ventricular ejection fraction (LVEF) from 30% to 75% within 1 week. One year after the diagnosis the patient is in good health, with steady normal LVEF. The rapid recovery, which was immediately subsequent to the administration of high-dose IVIG, suggests that this kind of treatment has been effective in our patient with acute myocarditis.

Acute Disease↗

Idiopathic pulmonary hemosiderosis in an adult. Favourable response to azathioprine.

Idiopathic pulmonary hemosiderosis (IPH) is a rare disorder characterised by intermittent, diffuse alveolar hemorrhage (DAH). Although an inflammatory pulmonary capillaritis can be evidenced in most patients with DAH, IPH is a distinct entity in which pulmonary inflammatory alterations are lacking. Most cases occur in children, although the disease has been exceptionally reported in adults too. Here, we, describe a case of IPH in a 30-year-old woman who was admitted to our hospital because of recurrent episodes of hemoptysis since the age of 21. IPH was diagnosed on the basis of: 1) an open lung biopsy showing focal alveolar edema and hemorrhage without parenchymal inflammatory alterations, 2) a bronchoalveolar lavage showing hemosiderin-laden macrophages, and 3) exclusion of infectious or immunologic causes of hemoptysis. Prednisone administration could control the disease, but every attempt to lower the dose to less than 25 mg per day was followed by recurrence of hemoptysis. Then, azathioprine was started, and after three months prednisone was gradually tapered to the dose of 10 mg per day, without any relapse of the disease. These findings indicate that azathioprine, in combination with prednisone, may be an effective therapy for IPH and suggest that an immunologic mechanism could be involved in the pulmonary capillary damage underlying alveolar bleeding.

Adult↗

Alpha-melanocyte-stimulating hormone in normal human physiology and disease states.

Over the past two decades, research in animal models has indicated that alpha-melanocyte-stimulating hormone (alpha-MSH) has potent anti-inflammatory properties. Furthermore, recent data show that the peptide has antimicrobial effects and probably contributes to innate immunity. alpha-MSH, which is produced by many extrapituitary human cells, should no longer be considered solely a pituitary hormone; rather, it should be viewed as a ubiquitous modulatory peptide.

Animals↗

Chronic systemic capillary leak syndrome. Report of a case and review of the literature.

Systemic capillary leak syndrome (SCLS) is a rare condition characterized by recurrent episodes of generalized oedema and severe hypotension, associated with paraproteinaemia. In addition to the acute form, a few cases of chronic SCLS have been reported. We describe a 64-year-old woman who was hospitalized because of a 6-month history of progressive generalized oedema with pericardial and pleural effusions, associated with a serum paraprotein. Clinical and laboratory findings were consistent with a chronic form of SCLS. Treatment with prednisone, furosemide and theophylline was started, which led to a gradual improvement in 2 weeks and a persistent remission after 9 months. This report indicates that SCLS may occur in a chronic form, which seems to be responsive to a therapeutic regimen with prednisone, furosemide, and theophylline.

Capillary Leak Syndrome↗

Plasma concentrations of alpha-melanocyte-stimulating hormone are elevated in patients on chronic haemodialysis.

BACKGROUND: Clinical and/or laboratory signs of systemic inflammation occur frequently in patients undergoing long-term haemodialysis. It is likely, therefore, that a compensatory release of endogenous anti-inflammatory molecules occurs to limit host reactions. The aim of the present research was to determine if the potent anti-inflammatory peptide alpha-melanocyte-stimulating hormone (alpha-MSH), a pro-opiomelanocortin derivative, is increased in plasma of haemodialysis patients. Because endotoxin and cytokines induce alpha-MSH in vivo and in vitro, we also measured plasma concentrations of endotoxin, interleukin-6 (IL-6), and tumour necrosis factor alpha (TNF-alpha), and the two circulating products of activated monocytes, nitric oxide (NO) and neopterin. METHODS: Thirty-five chronic haemodialysis patients, 20 patients with chronic renal failure not yet on dialysis, and 35 normal controls were included in the study. In the haemodialysis group, blood samples were obtained before and at the end of a dialysis session. Plasma alpha-MSH was measured using a double antibody radioimmunoassay, and IL-6, TNF-alpha, and neopterin using specific enzyme-linked immunosorbent assays. Plasma nitrites were determined by a colorimetric method, and endotoxin with the quantitative chromogenic LAL (limulus amoebocyte lysate) method. RESULTS: Mean plasma alpha-MSH was higher in haemodialysis patients than in control subjects, with the peptide concentrations being particularly elevated in dialysed patients with detectable endotoxin. High alpha-MSH concentrations were observed in the pre-dialysis samples, with no substantial change at the end of the dialysis session. Plasma concentrations of IL-6, TNF-alpha, neopterin, and NO were generally elevated in chronic haemodialysis patients and there was a negative correlation between circulating alpha-MSH and IL-6. In patients with renal failure not yet on dialysis, mean plasma alpha-MSH was similar to that of normal subjects. CONCLUSIONS: alpha-MSH is increased in the circulation of chronic haemodialysis patients and particularly so in case of detectable endotoxaemia. Reduction of renal clearance is unlikely to contribute to the observed rise of the peptide because alpha-MSH concentration is not increased in patients with chronic renal failure who are not yet on dialysis. It is likely that dialysis-associated endotoxaemia, directly and/or through cytokine release, enhances the production of the anti-inflammatory mediator alpha-MSH that limits host reactions.

Adult↗

Plasma concentrations and anti-L-cytokine effects of alpha-melanocyte stimulating hormone in septic patients.

OBJECTIVES: The aim of this research was to investigate endogenous concentrations and anti-cytokine effects of the antiinflammatory peptide alpha-melanocyte stimulating hormone (alpha-MSH) in patients with systemic inflammation. The objectives were to determine the following: changes over time of plasma alpha-MSH and relationship with patient outcome, correlation between plasma alpha-MSH and tumor necrosis factor (TNF)-alpha plasma concentration and production in whole blood samples, and influences of alpha-MSH on production of TNF-alpha and interleukin (IL)-1beta in whole blood samples stimulated with lipopolysaccharide (LPS). DESIGN: Prospective, nonrandomized, clinical study. SETTING: Intensive care unit of a university hospital. PATIENTS: A total of 21 patients with sepsis syndrome/septic shock and an equal number of healthy volunteers. INTERVENTIONS: Circulating alpha-MSH and TNF-alpha concentrations and TNF-alpha production in supernatants of LPS (1 ng/mL)-stimulated whole blood were measured repeatedly. To determine whether alpha-MSH can modulate production of TNF-alpha and IL-1 beta, these cytokines were measured in whole blood samples stimulated with LPS (1 ng/mL) in the presence or absence of concentrations of the peptide. MEASUREMENTS AND MAIN RESULTS: Plasma alpha-MSH was low in early samples and gradually increased in patients who recovered but not in those who died. There was a negative correlation between plasma concentrations of alpha-MSH and TNF-alpha. In blood samples taken at early phases of sepsis syndrome, production of TNF-alpha was reduced relative to control values; such production increased in patients who recovered but not in those who died. Addition of alpha-MSH to LPS-stimulated whole blood samples inhibited production of TNF-alpha and IL-1beta in a concentration-dependent manner. CONCLUSIONS: In patients with systemic inflammation, there are substantial changes over time in plasma concentrations of alpha-MSH that are reduced in early phases of the disease. Reduction of this endogenous modulator of inflammation could be detrimental to the host. Addition of alpha-MSH to LPS-stimulated blood samples reduces production of cytokines involved in development of septic syndrome. This inhibition by alpha-MSH, a peptide that is beneficial in treatment of experimental models of sepsis, might therefore be useful to treat sepsis syndrome in humans.

Adult↗

The neuropeptide alpha-MSH in host defense.

The presence of the ancient peptide alpha-melanocyte-stimulating hormone (alpha-MSH) in barrier organs such as gut and skin suggests that this potent anti-inflammatory molecule may be a component of the innate host defense. In tests of antimicrobial activities, alpha-MSH and its fragment KPV showed inhibitory influences against the gram-positive bacterium Staphylococcus aureus and the yeast Candida albicans. Anti-tumor necrosis factor and antimicrobial effects of alpha-MSH suggest that the peptide might likewise reduce replication of human immunodeficiency virus (HIV). Treatment with alpha-MSH reduced HIV replication in chronically and acutely infected human monocytes. At the molecular level, alpha-MSH inhibited activation of the transcription factor NF-kappa B known to enhance HIV expression. alpha-MSH that combines antipyretic, anti-inflammatory, and antimicrobial effects could be useful in the treatment of disorders in which infection and inflammation coexist.

Animals↗

Sarcoidosis in a patient with 5q-myelodysplasia. A possible pathogenetic link between the two diseases.

This study describes the occurrence of sarcoidosis with lung and skin involvements in a 56-yr-old woman who suffered from 5q-myelodysplastic syndrome since the age of 50. The 5q-myelodysplastic syndrome is marked by deletion of the long arm of chromosome 5, which carries the genes coding for T-helper cell 2 cytokines, such as interleukins-3, -4 and -5, and granulocyte-macrophage colony-stimulating factor. Although the aetiology of sarcoidosis remains unclear, sarcoid granulomatous inflammation is marked by predominant expression of T-helper cell 1 cytokines, with reduced expression of T-helper cell 2 cytokines. The authors suggest that 5q-abnormality may have predisposed to sarcoidosis through an imbalance in the cytokine network, caused by the deletion of genes coding for T-helper cell 2 cytokines.

Chromosome Deletion↗

alpha-MSH in systemic inflammation. Central and peripheral actions.

Until recently, inflammation was believed to arise from events taking place exclusively in the periphery. However, it is now clear that central neurogenic influences can either enhance or modulate peripheral inflammation. Therefore, it should be possible to improve treatment of inflammation by use of antiinflammatory agents that reduce peripheral host responses and inhibit proinflammatory signals in the central nervous system (CNS). One such strategy could be based on alpha-melanocyte stimulating hormone (alpha-MSH). Increases in circulating TNF-alpha and nitric oxide (NO), induced by intraperitoneal administration of endotoxin in mice, were modulated by central injection of a small concentration of alpha-MSH. Inducible nitric oxide synthase (iNOS) activity and iNOS mRNA in lungs and liver were likewise modulated by central alpha-MSH. Increase in lung myeloperoxidase (MPO) activity was significantly less in lungs of mice treated with central alpha-MSH. Proinflammatory agents induced by endotoxin were significantly greater after blockade of central alpha-MSH. The results suggest that antiinflammatory influences of neural origin that are triggered by alpha-MSH could be used to treat systemic inflammation. In addition to its central influences, alpha-MSH has inhibitory effects on peripheral host cells, in which it reduces release of proinflammatory mediators. alpha-MSH reduces chemotaxis of human neutrophils and production of TNF-alpha, neopterin, and NO by monocytes. In research on septic patients, alpha-MSH inhibited release of TNF-alpha, interleukin-1 beta (IL-1 beta), and interleukin-8 (IL-8) in whole blood samples in vitro. Combined central and peripheral influences can be beneficial in treatment of sepsis.

Animals↗

Elevated concentrations of plasma alpha-melanocyte stimulating hormone are associated with reduced disease progression in HIV-infected patients.

To determine whether concentrations of the anti-inflammatory peptide alpha-melanocyte stimulating hormone (alpha-MSH) are associated with accelerated or reduced disease progression in patients with HIV infection, plasma concentrations of alpha-MSH and two other anticytokine molecules, interleukin-1 receptor antagonist (IL-1 ra) and soluble tumor necrosis factor receptor (s TNF r), were taken repeatedly from HIV-positive patients over a 1-year period. Samples from 87 patients were collected by using special precautions to ensure accurate measurement of the peptide. Alpha-MSH concentrations were determined by radioimmunoassay; IL-1 ra and s TNF r concentrations were measured by using enzyme-linked immunosorbent assays. Clinical and immunologic variables were recorded to determine whether there is an association between cytokine antagonist concentrations and disease progression. Elevated concentrations of circulating alpha-MSH were associated with reduced progression of the disease. Circulating alpha-MSH was greater in non-progressors than in progressors; the association between elevated alpha-MSH and reduced disease progression was even more pronounced in patients with baseline CD4+ T cell counts less than 200/microL. No such association was observed for the other two anticytokine molecules, and there was no significant correlation between the plasma concentration of either cytokine antagonist and alpha-MSH. The present evidence and previous findings indicate that elevated concentrations of alpha-MSH are associated with reduced disease progression in HIV-infected patients.

Adult↗

The neuropeptide alpha-MSH in HIV infection and other disorders in humans.

We measured plasma concentration of alpha-melanocyte-stimulating hormone (alpha-MSH), a proopiomelanocortin derivative that modulates pyrogenic and proinflammatory effects of cytokines, in infectious and inflammatory disorders in humans to learn if changes in this peptide take place in naturally occurring disease. alpha-MSH was elevated in HIV-infected patients of the CDC groups III and IV. Although the peptide increased in the circulation of normal subjects injected with endotoxin, it was reduced in patients with septic syndrome. alpha-MSH was found in the synovial fluid of arthritis patients, and its concentration was greater in the forms of arthritis marked by greater inflammation. We found that alpha-MSH is increased in the circulation of patients with acute myocardial infarction receiving thrombolytic therapy. Plasma concentrations of alpha-MSH is increased in the circulation of patients with acute myocardial infarction receiving thrombolytic therapy. Plasma concentrations of alpha-MSH were lower in healthy elderly subjects than in young controls. Because an excess of proinflammatory cytokines can have detrimental effects, we investigated the influences of alpha-MSH on the production of interleukin-1 (IL-1) and tumor necrosis factor (TNF) in HIV-infected patients and in patients with septic syndrome. Production of these cytokines in whole-blood samples stimulated with endotoxin was significantly reduced by treatment of blood with alpha-MSH. alpha-MSH has been injected into at least 106 human subjects to study its effects on pituitary function, menstrual bleeding, and tanning. The peptide was always well tolerated. alpha-MSH administration could open new perspectives in treatment of inflammatory diseases in humans.

Acquired Immunodeficiency Syndrome↗