Sjogren's syndrome: an update on clinical, basic and diagnostic therapeutic aspects

The 11th International Symposium for Sjogren's syndrome was held in Athens, Greece in September 2011. This symposia is part of a long series of meetings that have attempted to meet the needs of both scientists and physicians in improving the healthcare of their patients with Sjogren's syndrome. Sjogren's syndrome affects almost 0.5% of the general population and is second only to rheumatoid arthritis amongst the systemic autoimmune diseases. More importantly, it has daily implications for the millions of sufferers around the world. The goal of this meeting, which included nearly 200 abstracts and invited lectures, was to address the critical needs in the clinical practice of Sjogren's syndrome. This volume is a composite of select papers that were presented at this meeting and attempts to provide a critical overview of clinical and basic science. The volume includes a variety of themes and, importantly, raises issues that are still unresolved but which are important in our future diagnostic and therapeutic efforts.     

Mucopolysaccharidosis IVA (Morquio A syndrome): clinical, biological and therapeutic aspects

Mucopolysaccharidosis IVA (MPS IVA; Morquio A disease) is an autosomal recessive lysosomal storage disorder caused by a genetic deficiency of the N-acetylgalactosamine-6-sulfate sulfatase (GALNS; E.C.3.1.6.4). GALNS is required to degrade keratan sulfate (KS) and chondroitine-6-sulfate (C6S). The accumulation of undegraded substrates in lysosomes of the affected tissues leads to a systemic bone dysplasia. Total urine glycosaminoglycans (GAG) in patients with MPS IVA are close to the normal range so it is difficult to distinguish this disease based on urine GAG excretion. Another potential disease marker could be KS levels in urine and plasma. Although the enzymatic diagnosis of affected patients with MPS IVA can be made, the detection of obligate heterozygotes by enzymatic measurement is less reliable because of a marked overlap of GALNS in fibroblasts or leucocytes from affected phenotype and normal controls. The genetic heterozygoty of MPS IVA has been facilitated by the isolation and characterization of the full lengh cDNA encoding human GALNS. Conventional therapy is symptomatic and limited to palliative procedures, which have virtually no impact upon mortality. To date, there is still no general consensus about the effectiveness of bone marrow transplantation. In the future, gene therapy could represent a great therapeutic improvement.     

Alexithymia, clinical and therapeutic aspects

The clinical observations on alexithymia which were initiated by Sifneos and Nemiah in the earlier 1970s have given rise to a host of studies with implications beyond the psychosomatic field of enquiry. Is alexithymia a pathology of affect or a character neurosis; is it primary or secondary; genetic or developmental? Is it an adaptational deformation related to social class and low psychological sophistication, a life style or a cerebral deficit? Is it global and consistent (trait) or partial and temporary (state)? Is it part of the necessary and sufficient condition for the development of a psychosomatic symptom or is it a nonspecific autoplastic alteration? It is quite possible that alexithymia is one of several mediating processes between stress and disease along with genetic susceptibility, developmental variables, context and reaction to untoward life events, coping dispositions, psychosocial support and sociocultural factors. Therapeutic approaches would depend on whether we are dealing with a primary affectless condition or a secondary one. A differential diagnosis is essential since self-numbing following psychic trauma or a pathological grief, masked and atypical depression are treatable. Blocking of affect may have dire effects on the psychosomatic economy and on the capacity for intimacy. Muscular and psychological rigidity, weariness, ennui and anhedonia may be the only clues to the presence of alexithymia. Since we may be dealing with a spectrum disorder, there is no single treatment modality. There are no controlled studies on the use of psychotropic drugs and psychoanalytic-oriented and behavioral approaches have been shown to be of some benefit.     

Gaucher disease: clinical, genetic and therapeutic aspects

Gaucher disease (GD) is one of the most prevalent lysosomal storage disorders and one of the rare genetic diseases for which therapy is now available. Partial deficiency of glucocerebrosidase is associated with parenchymal disease of the liver, spleen, and bone marrow with concomitant anaemia and thrombocytopenia in non-neuronopathic, type 1, Gaucher disease. Severe deficiency of glucocerebrosidase caused by disabling mutation is additionally associated with neurological manifestations in the less common type 2 and type 3 Gaucher diseases. Outside of the Ashkenazi Jewish community, a high molecular diversity is observed. Clarification of genotype-phenotype relationship and the identification of modifier loci that impact on Gaucher disease phenotypes remain a critical area for research. Recombinant glucocerebrosidase (imiglucerase) is an effective mean of treating type 1 Gaucher disease and should be initiated early on in life. Amelioration of hepatosplenomegaly and of haematological manifestations is usually apparent within six months. Bone disease responds more slowly. Imiglucerase has recently been approved for the treatment of type 3 Gaucher disease. Enzyme replacement therapy cannot reverse the neurological deficits in type 2 or type 3 Gaucher disease. This should prompt further research on substrate deprivation and gene therapy.     

The importance of tuberculosis in the acquired immunodeficiency syndrome. The clinical and therapeutic aspects

These is presented a study of 50 patients suffering TB and AIDS. The universe was divided in two: group I, when TB was considered the first manifestation of AIDS; (27 males and 2 females). Group II, when TB was preceded by some opportunistic infection, some kind of cancer, or some clinical symptoms compatible with wasting syndrome; (20 males and 1 female). There was no difference between the two groups regarding epidemiology, since homo-bisexuality was the most frequent among males. Neither were significantly different the clinical features of TB in both groups, and the most frequent symptoms were: fever, productive cough and painful lymphadenopathy. Both groups showed miliary infiltration on the lung X-rays; lymph nodes were the most frequent extrapulmonary localization. The only significant difference was found when the mortality was compared group I, 10 patients (34.4%) vs 16 (76%) from group II (p less than 0.01). An other part of the study is related with the efficacy of rifampin and isoniazide (31 cases), compared to their efficiency when these drugs are used combined with a third one (10 cases); the results showed no significant difference.     

Restenosis estimation at the clinical level: methodologic and angiographic aspects

Quantitative coronary angiography is the most objective and reproducible method for estimating restenosis after coronary angioplasty. Unfortunately, it does not strictly reflect the clinical restenosis. Numerous angiographic criteria have been defined, from the binary restenosis (>50% stenosis at the site dilated) routinely used by the clinician, to more sophisticated quantitative criteria in order to quantify the intimal hyperplasia, more objective but requiring rigorous criteria. However, new quantitative coronary analysis softwares have not been developed during the last years and each team had to evaluate its intra and inter observer variability. However, angiographic method is still the gold standard method for restenosis estimation, the ideal would be to defined an angiographic restenosis clinically consistent and well correlated with major cardiovascular events.     

Melkersson-Rosenthal syndrome: clinical, pathologic, and therapeutic considerations.

Melkersson-Rosenthal syndrome (MRS) has been described as a rare disease. Localized swelling (usually of the lips) with noncaseating epithelioid granuloma is necessary for diagnosis. We report 11 patients with biopsy-proven MRS. Mean age was 28 years (range 12-47 years). Mean duration of lesions was 4.4 years. Lip biopsy confirmed typical sarcoid-like granuloma. Five additional patients with typical symptoms are awaiting or refused lip biopsy. Clinically all patients presented with localized swelling of the lips. Treatment with clofazimine (100 mg 4 times weekly for 3-11 months) was associated with complete remission in 5/10 patients and clinical improvement in 3/10 patients with moderate constant swelling. Two patients (one severe and one moderate swelling) failed to respond to treatment. Rebiopsy in four patients confirmed improvement with disappearance or decreased granulomatous inflammation in 3/4. Complete spontaneous remission was also seen in three untreated patients. We conclude MRS is not uncommon, clofazimine may be effective treatment in moderate lesions and spontaneous remissions can occur.     

GM1 gangliosidosis: review of clinical, molecular, and therapeutic aspects

GM₁ gangliosidosis is a lysosomal storage disorder due to deficiency of the β-galactosidase enzyme. This deficiency results in accumulation of GM₁ gangliosides and related glycoconjugates in the lysosomes leading to lysosomal swelling, cellular damage, and organ dysfunction. The disease is lethal in the infantile and juvenile forms. To date, up to 102 mutations distributed along the β-galactosidase gene (GLB1) have been reported. This review gives an overview of the clinical and molecular findings in patients with GM₁ gangliosidosis. Furthermore, it describes therapeutic approaches which are currently under investigation in animal models of the disease.     

Fechtner syndrome: clinical and genetic aspects

Fechtner syndrome, a variant of Alport syndrome, was first reported by Peterson et al. [1985]. It is characterized by nephritis, hearing loss, eye abnormalities, macrothrombocytopenia, and leucocyte inclusions, present in varying combinations in several members of the same family. This is the second family reported; 16 relatives are affected. The clinical manifestations of the syndrome are delineated. The pattern of inheritance is autosomal dominant. The hematologic abnormalities are similar to those detected in May Hegglin anomaly. They are present in every affected relative and may be present at birth. The feasibility of prenatal diagnosis is discussed.     

Roberts syndrome: clinical and cytogenetic aspects

Roberts syndrome is reported in two sibs of consanguineous parents. Both infants had severe tetraphocomelia, facial clefting, and other serious malformations. In addition they were found to have an unusual cytogenetic abnormality with distortion of the normal sister chromatid relationship in many chromosomes.     

The trans-cerebral veins: normal and non-pathologic angiographic aspects

Summary The trans-cerebral v. have long been described, but there is little or no knowledge of their function and dysfunction. They are the site of fundamental interchange across the blood-brain barrier, a unique process within the organism. Two systems can be structurally distinguished: the venous system draining the white matter and the trans-cerebral anastomotic system. The former seems to be associated with the nutrition and drainage of the parenchyma, and is rendered visible at angiography by anatomic variations based on developmental venous anomalies. The anastamotic trans-cerebral ventriculo-cortical system seems concerned with the regulation of reabsorption of the cerebrospinal fluid. It is visualized only in exceptional situations where an increased flow (arteriovenous shunt) is combined with obstruction of the normal routes of venous drainage and collateral circulation. It usually functions in the ventriculo-cortical direction. No specific dysfunction of this system is currently recognized.

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Les Veines trans-cérébrales: aspect angiographique normal et anormal

Résumés Les v. trans-cérébrales sont décrites depuis longtemps, mais leur fonctionnement et leur dysfonctionnement sont peu ou pas connus. Elles sont le siège d'échanges fondamentaux sur un mode unique dans l'organisme: la barrière hémato-encéphalique. Architecturalement on distingue 2 systèmes: le système veineux drainant la substance blanche et le système anastomotique trans-cérébral. Le premier semble lié à des fonctions de nutrition et de drainage du parenchyme; les anomalies veineuses de développement constituent des variations anatomiques qui le rendent angiographiquement visible. Le système anastomotique trans-cérébral ventriculo-cortical semble prédisposé à la régulation de la résorption du liquide céphalo-rachidien; il n'est visible que dans des situations exceptionnelles associant une augmentation de débit (shunt artério-veineux) à des obstacles veineux des voies habituelles de drainage et de circulation collatérale. Il est mis à contribution, le plus souvent dans le sens ventriculo-cortical. Aucun dysfonctionnement spécifique de ce système n'est actuellement connu.

     

The menopause and the female larynx,clinical aspects and therapeutic options: A literature review

During lifetime the female larynx is very sensitive to sex hormone fluctuations. The menopause forms a critical event in a women's life and also affects the laryngeal tissues. The present report gives an overview of the recent literature about the impact of the menopause on the female larynx and vocal quality. The article discusses the symptoms, aetiology and different treatment options for laryngeal changes during the menopause. The literature pertaining to the impact of the menopause on the voice and the larynx was reviewed to provide a critical summary about the menopausal voice, aetiology and therapeutic options.     

Comparison of stent graft, sirolimus stent, and bare metal stent implanted in patients with acute coronary syndrome: clinical and angiographic follow-up

Strozzi and Anić