Varicella in immunocompromised patients.
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Biomedical subjects
Publications and source records attributed to S Vinzio.
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OBJECTIVES: Subclinical hypothyroidism defined by the presence of elevated TSH levels but normal free T4 level is a common situation. Its consequences on health are yet on debate and the interest of a precocious treatment remains surrounded by controversy. KEY POINTS: The relationship between subclinical hypothyroidism and cardiovascular disease has been evaluated by several cross-sectional and longitudinal studies. Subclinical hypothyroidism has direct but subtle effects on the heart function, on the peripheral vascular resistance, and is associated with a mild elevation of LDL-cholesterol levels; all abnormalities may be partly reversed by a thyroxine supplementation. Data of the literature give insufficient evidence as to whether subclinical hypothyroidism is an independent cardiovascular risk factor. However treatment of subjects with TSH levels up or near to 10 mU/l would probably be beneficial in the prevention of cardiovascular disease. FUTURE PROSPECTS: Based on observational and interventional studies there are some arguments on the benefit of euthyroidism restoration only in patients with TSH levels superior to 10 mU/l.
INTRODUCTION: Bilateral parotid enlargement are presenting features of some metabolic and systemic disease but also of chronic emesis. CASE RECORD: A 24-year old woman consulted during three years many physicians asking for the treatment of a painless parotid swelling confusing with a Sjogren's syndrome. After an initial denial, the weight history, alteration of tooth wear and hypokaliemia conducted to admit a self inducing vomiting with bulimia nervosa. CONCLUSION: Gender, young age, weight history, tooth alteration and electrolytic disorders are the main diagnostic tool of this dissimulated etiology of parotid swelling.
Systemic diseases located in hypothalamo-pituitary region can slowly induce pituitary deficiency, diabetes insipidus and morphological abnormalities. The aim of this study is to review recent clinical data about diagnosis of these rare diseases, with a focus on granulomatous diseases: histiocytosis and sarcoidosis. Recent clinical studies on histiocytosis have improved our knowledge about endocrine expression of the disease in children and in adults as well. Diabetes insipidus is the most frequent condition, described mainly in children. GH deficiency is the most frequent pituitary deficit in children and adult patients. During neurosarcoidosis, diabetes insipidus is the most frequent condition and gonadotropic deficiency is the most frequent deficit but GH has not been systematically studied. MRI allows visualisation of some lesions and is very useful to follow the disease course. Diagnosis of these diseases is made by clinical evaluation of all the sites and by pathological analysis of biopsies of peripheral lesions. While pituitary hormone replacement therapy does not seem to raise specific problems in these diseases, etiological treatments are not yet available and indications for antimitotic or immunomodulatory treatment are sometimes discussed.
AIM: Obesity is a risk factor for cardiovascular diseases and venous thromboembolism. Circulating procoagulant microparticles (MP) have been described in various clinical situations associated with thrombosis and in diabetic patients. The aim of this preliminary study was to evaluate the presence of MP in obese patients without any other vascular risk factor in particular diabetes. METHODS: Fifty-eight obese women <50 year-old without other cardiovascular risk factors were recruited from a single out-patient nutrition clinic. They were compared to 45 age-matched healthy normal weight controls. Main outcome was MP levels in patients and controls. Relationships between MP concentrations and parameters reflecting insulin resistance in patients were also studied. RESULTS: Obese patients were 33.3 +/- 1.2 years old and had a mean BMI of 42.4 +/- 0.9 kg/m2. There vas a greater proportion of smokers in the obese group (34.5 vs 15.6%). Mean MP levels were markedly higher in obese patients compared to controls (10.6 +/- 0.5 vs 3.2 +/- 0.3 nMPSeq, P < 0.001). There was no difference in MP concentrations between smokers and non smokers. In the obese group, there was a negative correlation between MP and BMI (r = -0.265, P < 0.05) but no relationship could be established between MP concentrations and markers of insulin resistance. CONCLUSION: This increase in circulating MP levels reflects cell activation and could account for the increased risk of thrombotic complications in obesity. Further studies are ongoing to explore the relationships between MP levels and coagulation markers and to assess the effect of weight reduction.
With the introduction of automated assays for measuring serum cobalamin levels over the last decades, the hematological manifestations related to cobalamin deficiency have been changed from the description reported in 'old' studies or textbooks. We studied the hematological manifestations or abnormalities in 201 patients (median age: 67 +/- 6 years) with well-documented cobalamin deficiency (mean serum vitamin B12 levels 125 +/- 47 pg/ml) extracted from an observational cohort study (1995-2003). Assessment included clinical features, blood count and morphological review. Hematological abnormalities were reported in at least two-third of the patients: anemia (37%), leukopenia (13.9%), thrombopenia (9.9%), macrocytosis (54%) and hypegmented neutrophils (32%). The mean hemoglobin level was 10.3 +/- 0.4 g/dl and the mean erythrocyte cell volume 98.9 +/- 25.6 fl. Approximately 10% of the patients have life-threatening hematological manifestations with documented symptomatic pancytopenia (5%), 'pseudo' thrombotic microangiopathy (Moschkowitz; 2.5%), severe anemia (defined as Hb levels <6 g/dl; 2.5%) and hemolytic anemia (1.5%). Correction of the hematological abnormalities was achieved in at least two-thirds of the patients, equally well in patients treated with either intramuscular or oral crystalline cyanocobalamin. This study, based on real data from a single institution with a large number of consecutive patients with well-documented cobalamin deficiency, confirms several 'older' findings that were previously reported before the 1990s in several studies and in textbooks.
KEY POINTS: Thyroid hormones affect cardiac myocytes as well as the smooth muscle and endothelial cells of the vascular wall. Free 3,53'-L-triiodothyronine (FT3) and its specific nuclear receptor modulate the transcription of various proteins, principally those involved in the myocyte contractile apparatus (myosin heavy chains), and the regulation of intracellular calcium flux (sarcoplasmic reticulum Ca2+ATPase). Thyroid hormones also have non-genomic effects that work rapidly, complement the effects described above, and are related to alterations in the properties of many channels and membrane receptors, especially in the sinoatrial mode. Thyroid hormones also affect the smooth muscle and endothelial cells of the vascular walls and reduce systemic vascular resistance. These effects on cardiac and vascular cells globally explain the cardiac manifestations (especially the inotropic and chronotropic effects) observed during dysthyroidism, particularly in hyperthyroidism where they are often in the forefront (positive inotropic and chronotropic effects).
KEY POINTS: Thyroid hormones affect the vascular system, including the diastolic and systolic functioning of the heart. Resting heart rate increases early in hyperthyroidism (cardiac contractility expands due to improved ventricular loading and decreased systemic vascular resistance). Paradoxically, these hemodynamic alterations progressively reduce cardiac performance on effort (changes in diastolic, then systolic functioning) and finally at rest (modification in ventricular loading following tachycardia or atrial fibrillation), especially in cases of underlying heart disease (in the elderly). Hypothyroidism has an inverse hemodynamic effect and is less noisy, usually limited to relative bradycardia. The morbidity and mortality associated with hypothyroidism are apparently related to the atherogenic and prothrombotic vascular modifications that follow thyroid hormone deficiency, whereas heart failure and particularly atrial fibrillation and its thromboembolic complications are the primary consequences of hyperthyroidism. In both cases, return to normal thyroid levels corrects the cardiac abnormalities caused by the dysthyroidism. Dysthyroidism (hypo- or hyperthyroidism) occurs in 10 to 20% of the patients treated with amiodarone for arrhythmia. Because of its potential seriousness, some clinical or laboratory tests are necessary before initiating treatment, and specific clinical surveillance should be scheduled, including laboratory tests.
KEY POINTS: Although the cardiovascular consequences of clinical or "overt" dysthyroidism are well known and treatment relatively well established, subclinical dysthyroidism remains a controversial topic, both regarding its cardiovascular effects and the best methods for its management. Subclinical hyperthyroidism is frequent among the elderly, usually associated with multinodular goiter. Although several epidemiologic studies have demonstrated that subclinical hyperthyroidism is associated with an increased risk of atrial fibrillation and high cardiovascular mortality, solid practical data on which management can be based are not currently available. The risks related to subclinical hypothyroidism appear essentially vascular but a conclusive assessment must await further epidemiologic surveys.
This case report describes a 31-year-old woman with a neglected ornithine carbamoyltransferase deficiency, admitted for a hyperammonaemic encephalopathy induced by a commercial very low-energy diet. To our knowledge, this is the first reported case and it underlines the potential risk of such a diet in patients with undiagnosed or neglected ornithine carbamoyltransferase deficiency.
BACKGROUND: In multicellular organisms, apoptosis and subsequent microparticle shedding play a key role in homeostasis. Having long been considered as << cellular dust >>, microparticles released in biological fluids upon cell activation or apoptosis appear as multifunctional bioeffectors involved in the modulation of key functions including immunity, inflammation, hemostasis and thrombosis, angiogenesis. MP constitute reliable markers of vascular damage, accessible to biological detection whilst the cells they originate from remain sequestered in tissues or are promptly submitted to phagocytosis. RECENT FINDINGS: MP modulate biological functions of target cells through the transfer of cytoplasmic content, lipids and membrane receptors. The pharmacological modulation of circulating levels of microparticles could be of particular interest in thrombotic or inflammatory diseases, cancer or hemophilia. CONCLUSION: MP can now be viewed not only as a hallmark of cell damage but also as a true biological tool.
PURPOSE: Update of the adult cobalamin deficiencies. CURRENT KNOWLEDGE AND KEY POINTS: More precise definitions establish the true cobalamin deficiencies and determine their real epidemiology. The current clinical data suggest the concept of food-cobalamin malabsorption as the leading etiology of cobalamin deficiency. The new features of cobalamin deficiency include neurological, gynecological and vascular manifestations. Current treatment modalities include nasal, sublingual and oral cobalamin administration. PROSPECTS AND PROJECTS: Studies are in the way to establish the relevance of the new clinical manifestations and to validate the usefulness of oral cobalamin therapy.
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Heart rate variability (HRV) is a measure of the physiological variation of R-R intervals, reflecting the sympathovagal balance. In both overt and subclinical hyperthyroidism, a relative increase in sympathetic activity has been demonstrated, mainly due to a decrease in vagal activity. The modifications of HRV during orthostatism in normal subjects resemble those seen in hyperthyroidism. We have studied the response of 19 patients with overt hyperthyroidism and 12 with subclinical hyperthyroidism during orthostatism using HRV and compared the results to those of 32 healthy controls. In the three groups, the R-R intervals decreased in the same proportion after orthostatism. The low frequency power (LF)/[LF + high frequency power (HF)] ratio, which reflects the sympathetic tone, also increased in the same proportion in the three groups. However, the mechanisms of the modulation of the sympathovagal balance during orthostatism were different among the three groups. In controls, the relative increase of sympathetic tone after orthostatism was due principally to a decrease in vagal tone (reflected by decreased power in the HF band), while in overt hyperthyroidism, where the power in the HF band was already minimal in the lying position, there was a clear increase in the LF band power during orthostatism. The results were intermediate in the subclinical hyperthyroidism group, reflecting a continuum of effects of the thyroid hormone excess on the autonomic nervous system. Our study shows that despite an apparent normal cardiovascular adaptation to orthostatism in hyperthyroidism, the modulation of the autonomic nervous system is profoundly modified.
INTRODUCTION: Bone marrow transplantation (BMT) is based on destruction of the patient's bone marrow with rescue of haematopoietic stem cells from a donor. Chronic graft-vs-host disease (GVH) is the major complication post-BMT and mimics some autoimmune diseases, such as scleroderma, sicca syndrome, primary biliary cirrhosis and an increased prevalence of various autoantibodies. Other autoimmune-like manifestations have been reported as case reports or short series. The most common are myasthenia gravis, polymyositis, autoimmune cytopenias and Graves' disease or autoimmune hypothyroidism. CURRENT KNOWLEDGE AND KEY POINTS: These diseases occur mainly in association with chronic GVH. The pathophysiology of chronic GVH and other autoimmune-like diseases post-BMT remains poorly understood. Different mechanisms have been postulated. Most of the autoimmune events (either chronic GVH or more specific diseases) seem to be related to a poor or inadequate immunologic recovery post-BMT with an imbalance between autoregulatory and autoreactive lymphocytes. Microchimerism and molecular mimicry have been recently evocated. A minority of cases (autoimmune thyroid disorders) is attributed to the direct transfer of autoreactive cells from donor to patient (adoptive immunity). FUTURE PERSPECTIVES: Despite physiopathologic uncertainty, these autoimmune-like disorders post-BMT are an interesting model for primary autoimmune diseases.
INTRODUCTION: The rationale for the treatment of hypercholesterolemia in the elderly is less clear than in middle-aged patients because of several conceptual, epidemiological, economical facts, a higher prevalence of polypathology and a weaker relation between hypercholesterolemia and cardiovascular risk when age increases. CURRENT KNOWLEDGE AND KEY POINTS: However, cardiovascular events-stroke and myocardial infarction occur mainly in people aged more than 65 years. The data of recent randomised clinical trials have demonstrated that the use of statins in the elderly remained associated to a reduced all-cause mortality, cardiovascular mortality and stroke. Statins were effective in elderly with average LDL-cholesterol in primary and secondary prevention trials. The drug tolerance was as good as in middle-aged patients. However, convincing data concerning subjects over 80 are lacking. CONCLUSION: On the basis of disponible data it may be considered that statins are useful in older persons with a serum LDL cholesterol level above 1.3 g/l and or a high cardiovascular risk, with or without cardiovascular disease, when their life expectancy is consequent.
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DEFINING THE PROBLEM: Sub-clinical hypothyroidism, defined as a moderate and isolated increase in TSH levels, is a common syndrome and is the first phase of a progressive disease. However its treatment remains controversial. Some anamnestic, clinical and biological (anti-thyroperoxidase antibodies) parameters contribute in identifying the patients most likely to progress towards overt hypothyroidism. WHAT CAN BE EXPECTED OF TREATMENT? Several clinical studies have described cardiovascular, neuromuscular and lipid disorders in these patients, but administration of levothyroxine has provided varying results and does not enable the distinction between a pharmacological-like intrinsic effect of the thyroid hormone and the true benefits imputable to the correction of TSH, in the absence of any large interventional study. More studies are required to better identify the patients who will benefit most from hormone replacement.