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MYH9-Related Disorders.
No full textClinical characteristics.
MYH9-related disorders (MYH9RD) are characterized by large platelets (i.e., >40% of platelets >3.9 μm in diameter) and thrombocytopenia (platelet count <150 x 109/L), both of which are present from birth. MYH9RD is variably associated with young-adult onset of progressive sensorineural hearing loss, presenile cataract, elevation of liver enzymes, and renal disease manifesting initially as glomerular nephropathy. Before identification of the gene in which mutation is causative, MYH9, individuals with MYH9RD were diagnosed as having Epstein syndrome, Fechtner syndrome, May-Hegglin anomaly, or Sebastian syndrome based on the combination of different clinical findings at the time of diagnosis. However, the realization that they all are due to heterozygous pathogenic variants in MYH9 and that the clinical findings often worsen throughout life as a result of late onset of non-hematologic manifestations has led the four conditions to be regarded as one disorder, now known as MYH9RD.
Diagnosis/testing.
The diagnosis is established by the finding of typical MYH9 protein aggregates in neutrophils detected through immunofluorescence analysis of a peripheral blood smear and/or by the identification of a heterozygous pathogenic variant in MYH9. Absence of MYH9 protein aggregates in neutrophils excludes the diagnosis of MYH9RD.
Management.
Treatment of manifestations: For active hemorrhage, application of local measures, desmopressin (DDAVP), and antifibrinolytic agents are used; platelet transfusion is necessary for: hemorrhages not controlled by the above treatments, life-threatening bleeding, or hemorrhages at critical sites. Hearing loss, renal complications, and cataract are managed in a standard fashion; individuals with severe/profound deafness benefit from cochlear implantation.
Prevention of primary manifestations: Platelet transfusion, desmopressin, antifibrinolytic drugs, or eltrombopag can be used to reduce the risk of bleeding prior to surgery or invasive procedures; oral contraceptives may be effective in preventing or treating menorrhagia; regular dental care to prevent gingival bleeding.
Surveillance: In those with bleeding episodes, blood count at least every six months to identify anemia. In all affected individuals, annual urinalysis (including 24-hour protein or protein [albumin]/creatinine ratio on a spot urine sample) and measurement of serum concentration of creatinine prior to onset of renal disease; serum liver enzyme measurements and audiometric and ophthalmologic evaluations every three years.
Agents/circumstances to avoid: Drugs that inhibit platelet function or blood coagulation; ototoxic, nephrotoxic, and hepatotoxic drugs should be used only after careful assessment of risk versus benefit; hazardous noise and activities with high risk of injury should be avoided.
Evaluation of relatives at risk: Screen at-risk newborns with molecular genetic testing if the family-specific pathogenic variant is identified; otherwise assess platelet count and size.
Pregnancy management: Deliveries should be managed as they are in women with other forms of thrombocytopenia; a platelet count of ≥50 x 109/L is generally recommended for safe delivery.
Genetic counseling.
MYH9RD is inherited in an autosomal dominant manner. Approximately 35% of affected individuals represent simplex cases, half of whom have a documented de novo pathogenic variant. Each offspring of an individual with MYH9RD has a 50% chance of inheriting the pathogenic variant. Prenatal diagnosis for pregnancies at increased risk is possible if the pathogenic variant in the family is known
Low-level laser therapy and vibration therapy for the treatment of localized adiposity and fibrous cellulite
No full textIntroduction: In recent years, there has been an upsurge in the application of low-level laser therapy in various medical diseases. Additionally, vibration therapy is a new and effective measure to prevent muscular atrophy and osteoporosis, along with some general health-related beneficial effects of exercise on skeletal muscles such as improvement of endothelial function and an increased enzyme capacity of energy metabolism. The aim of this study was to evaluate the application of a 635 nm and 0.040W exit power per multiple diode laser in combination with vibration therapy for the application of non-invasive reduction of circumference in patients with localized adiposity and cellulite. Methods: The study enrolled men and women (N = 33) aged 18-64 years with localized adiposity or fibrous cellulite. The evaluation parameters were: photographic evaluation, perimetric evaluation, blood tests, ecographic evaluation, histological evaluation, and subjective and objective tests. Results: The results produced were statistically analyzed and resulted in a significant reduction of fat thickness when compared to the measurement prior to the treatment (P<0.0001). Moreover, subjective and objective tests, as well as ecographic and histological evaluations, confirmed the reduction of fat thickness. Conclusion: In this study we have demonstrated the safety and efficacy of the combination between low-level laser therapy and vibration therapy for the resolution of localized adiposity and fibrous cellulite. © The Author(s) 2013
A New Minimally Invasive Mesotherapy Technique for Facial Rejuvenation
Full text linkIntroduction: This study describes a pivotal clinical trial of a new minimally invasive mesotherapy technique for facial rejuvenation. Methods: The authors utilized two formulations: formulation A with hyaluronic acid, vitamins, amino acids, minerals, coenzymes, and antioxidant substances; formulation B with hyaluronic acid and idebenone. Fifty participants were enrolled in the study and divided in two groups. Group 1 (50-65 years) treated with formulation A. Group 2 (35-50 years) treated with formulation B. The groups underwent four sessions of mesotherapy involving multiple injections. Treatment was conducted at 15 day intervals. All participants had pre- and posttreatment photographs. Punch biopsies were taken from randomly selected participants, baseline and after 6 weeks, and stained for interleukin (IL)-6, IL- 1b, matrix metalloproteinase (MMP)-1, and collagen 1. Clinical evaluation was based on the Global Aesthetic Scale (GAIS) and on the Wrinkle Severity Rating Scale (WSRS). Results: The results produced were statistically analyzed and resulted in a significant and long-lasting effect on facial rejuvenation. Evaluation of photographs at 0, 1, and 2 months revealed significant clinical improvement: brightness, texture, and firmness of the skin. The analysis of the GAIS and WSRS scores in the two groups demonstrated statistically significant results after 2 months. The biopsies taken from randomly selected participants at baseline and after 3 months showed a decrease in IL- 1b, IL-6, and MMP1, and an increase in collagen 1. Conclusion: The new minimally invasive mesotherapy technique described can improve the clinical appearance of the skin in different age groups. © The Author(s) 2013
Inherited thrombocytopenias frequently diagnosed in adults.
No full textThe diagnosis of inherited thrombocytopenias is difficult for many reasons. First, as all rare diseases, they are little known by clinicians who, therefore, tend to suspect the most common forms. Secondly, making a definite diagnosis often requires complex laboratory techniques that are available only in a few centers. Finally, half of patients have forms that have not yet been described. As a consequence, many patients with inherited thrombocytopenias are misdiagnosed with immune thrombocytopenia and are at risk of receiving futile treatments. Misdiagnosis is particularly frequent in patients whose low platelet count is discovered in adult life, because in these cases even the inherited origin of thrombocytopenia may be missed. Making promptly the correct diagnosis is important since we recently learned that some forms of inherited thrombocytopenia predispose to other illnesses, as leukemia or kidney failure, and affected subjects therefore require close surveillance and, if necessary, prompt treatments. Moreover, medical treatment can increase platelet count in specific disorders, and affected subjects can therefore receive drugs instead of platelet transfusions when selective surgery is required. In this review we will discuss how to suspect, diagnose and manage inherited thrombocytopenias, with particular attention to the forms that frequently present in adults. Moreover, we describe four recently identified disorders that belong to this group of disorders often diagnosed in adults: MYH9-related disease, monoallelic Bernard-Soulier syndrome, ANKRD26-related thrombocytopenia and familial platelet disorder with predisposition to acute leukemia
Inherited thrombocytopenia: from gene to therapy
No full textBACKGROUND AND OBJECTIVES:
Inherited thrombocytopenias are a heterogeneous group of rare diseases characterized by a reduced number of blood platelets. Some of these diseases are exclusive to megakaryocytes and platelets, while in others the pathology extends to other cell types. Although the defective genes, coding for membrane glyoproteins, cytoskeleton components and intracellular signaling pathways, as well as transcription factors, have been identified in most cases, the pathophysiology of these disorders is often unknown. This review describes recent contributions to clinical and diagnostic aspects, biology and treatments of familial thrombocytopenias.
EVIDENCE AND INFORMATION SOURCES:
The information presented here derives from literature and the experience of the authors. The most relevant studies are critically analyzed and discussed.
STATE OF ART:
The clinical and laboratory features of most of the inherited thrombocytopenias have been reviewed. The different forms have been classified into 3 groups depending on platelet volume. Although this criterion is not completely satisfactory, it is one of the most useful in diagnostic algorithms. We report on recent advances in Wiskott-Aldrich and Bernard-Soulier syndromes, as well as in MYH9-related diseases, a new nosological entity that groups old distinct forms known as May-Hegglin anomaly, Sebastian, Fetchner, and Epstein syndromes. Other, less frequent forms are also discussed, including non-syndromic forms of mild thrombocytopenia that are genetically heterogeneous.
PERSPECTIVES:
In the past, inherited thrombocytopenias were considered exceedingly rare and the number of well-defined forms was very small. In the last few years, the widespread diffusion of electronic cell counters has allowed these conditions to be detected more frequently and several new entities have been identified through the co-ordinated efforts of physicians, biologists and geneticists. The pathogenesis of many new and old forms is being unraveled, thus providing insights on the molecular basis of platelet production and function. This knowledge will be a valuable resource for clinicians in the diagnostic approaches to such disorders
Inherited thrombocytopenias: from genes to therapy.
No full textBACKGROUND AND OBJECTIVES: Inherited thrombocytopenias are a heterogeneous group of rare diseases characterized by a reduced number of blood platelets. Some of these diseases are exclusive to megakaryocytes and platelets, while in others the pathology extends to other cell types. Although the defective genes, coding for membrane glyoproteins, cytoskeleton components and intracellular signaling pathways, as well as transcription factors, have been identified in most cases, the pathophysiology of these disorders is often unknown. This review describes recent contributions to clinical and diagnostic aspects, biology and treatments of familial thrombocytopenias.
EVIDENCE AND INFORMATION SOURCES: The information presented here derives from literature and the experience of the authors. The most relevant studies are critically analyzed and discussed.
STATE OF ART: The clinical and laboratory features of most of the inherited thrombocytopenias have been reviewed. The different forms have been classified into 3 groups depending on platelet volume. Although this criterion is not completely satisfactory, it is one of the most useful in diagnostic algorithms. We report on recent advances in Wiskott-Aldrich and Bernard-Soulier syndromes, as well as in MYH9-related diseases, a new nosological entity that groups old distinct forms known as May-Hegglin anomaly, Sebastian, Fetchner, and Epstein syndromes. Other, less frequent forms are also discussed, including non-syndromic forms of mild thrombocytopenia that are genetically heterogeneous.
PERSPECTIVES: In the past, inherited thrombocytopenias were considered exceedingly rare and the number of well-defined forms was very small. In the last few years, the widespread diffusion of electronic cell counters has allowed these conditions to be detected more frequently and several new entities have been identified through the co-ordinated efforts of physicians, biologists and geneticists. The pathogenesis of many new and old forms is being unraveled, thus providing insights on the molecular basis of platelet production and function. This knowledge will be a valuable resource for clinicians in the diagnostic approaches to such disorders
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