Multifaceted Presentations Research Articles

Serum Protein Profiling of Systemic Lupus Erythematosus and Systemic Sclerosis Using Recombinant Antibody Microarrays

Systemic lupus erythematosus (SLE) and systemic sclerosis (SSc) are two severe autoimmune connective tissue diseases. The fundamental knowledge about their etiology is limited and the conditions display complex pathogenesis, multifaceted presentations, and unpredictable courses. Despite significant efforts, the lack of fully validated biomarkers enabling diagnosis, classification, and monitoring of disease activity represents significant unmet clinical needs. In this discovery study, we have for the first time used recombinant antibody microarrays for miniaturized, multiplexed serum protein profiling of SLE and SSc, targeting mainly immunoregulatory proteins. The data showed that several candidate SLE-associated multiplexed serum biomarker signatures were delineated, reflecting disease (diagnosis), disease severity (phenotypic subsets), and disease activity. Selected differentially expressed markers were validated using orthogonal assays and a second, independent patient cohort. Further, biomarker signatures differentiating SLE versus SSc were demonstrated, and the observed differences increased with severity of SLE. In contrast, the data showed that the serum profiles of SSc versus healthy controls were more similar. Hence, we have shown that affinity proteomics could be used to de-convolute crude, nonfractionated serum proteomes, extracting molecular portraits of SLE and SSc, further enhancing our fundamental understanding of these complex autoimmune conditions.

Tuberculosis and malignancy

Tuberculosis (TB) and malignancy represent global threats claiming millions of lives and inflicting formidable suffering worldwide. Surprisingly, the pathophysiological and practical implications of their co-existence have received little attention. Therefore, we sought to review the available literature on the field and identify data regarding the association between TB and malignancy in order to highlight the neglected aspects of this association and probably derive clinically useful information. We searched PubMed up to June 2008 for case reports, case series, non-comparative and comparative studies that were written in English and reported data on the occurrence of both TB infection and a neoplastic disorder in the same patient(s). The development of mycobacterial infections in patients with immunocompromized conditions is well known and was considered outside the scope of this review. The synthesis of the available evidence enabled us to establish three different types of association between malignancy and TB: (i) the development of cancer on the background of a previous tuberculous infection; (ii) the concurrent existence of TB and malignancy in the same patient(s) or clinical specimen(s); and (iii) the diagnostic challenges arising from the multi-faceted presentations of these two disorders. We conclude that clinicians need to be aware of the protean manifestations of TB and cancer and maintain a high index of suspicion for simultaneous and/or misleading presentations. In addition, further research is required to determine if a tuberculous infection, being similar to other chronic infections and inflammatory conditions, may facilitate carcinogenesis.

The clinical spectrum of anti-GAD antibody-positive patients with stiff-person syndrome.

To evaluate the clinical spectrum of anti-GAD-positive patients with stiff-person syndrome (SPS) and provide reproducible means of assessing stiffness. SPS can be difficult to diagnose. Delineation of the clinical spectrum in a well defined population will increase diagnostic sensitivity. In 20 anti-GAD-positive patients with SPS (six men, 14 women), screened among 38 referred patients, the authors assessed symptoms and signs, degree of disability, associated conditions, and immunogenetic markers. Degree of bending, distribution of stiff areas, timed activities, and magnitude of heightened sensitivity were examined monthly for 4 months in five patients. Average age at symptom onset was 41.2 years. Time to diagnosis was delayed from 1 to 18 years (mean 6.2). Stiffness with superimposed episodic spasms and co-contractures of the abdominal and thoracic paraspinal muscles were characteristic. All had stiff gait and palpable stiffness in the paraspinal muscles. Stiffness was asymmetric or prominent in one leg in 15 patients (stiff-leg syndrome) and involved facial muscles in 13. In one patient spasms lasted for days (status spasticus). Twelve patients needed a cane and seven a walker due to truncal stiffness and frequent falls (average three to four per month). Distribution of stiffness and degree of heightened sensitivity were two reproducible indices of stiffness and spasms. Autoimmune diseases or autoantibodies were noted in 80% and an association of with DRss(1) 0301 allele in 70%. SPS is 1) frequently misdiagnosed due to multifaceted presentations and asymmetric signs, 2) disabling if untreated, and 3) associated with other autoimmune conditions.

Current perspectives in the surgery of multiple endocrine neoplasias.

Multiple endocrine neoplasia is an uncommon but fascinating condition. In this review we examine the multifaceted presentations, the diagnostic challenges and different management strategies for various syndromes. This is an attempt to share our knowledge and experience towards achieving better outcomes in the management of the diseases.

Review of pharmacologic and toxicologic effects of alcohol

Oral neglect and dental diseases are common; consumption of alcohol is common. To appreciate the frequency of alcoholism, the dental specialist must recognize that no persons will seek attention for alcoholism. Suspicion of alcohol related dental disease is the key. Heavy smoking, malnutrition, bleeding gingiva, cancer of the head and neck, and enlargement of the parotid glands should all raise a question of alcoholism. Alcohol affects most organ systems, but toxicity is extremely variable. Single organ systems may be severely damaged whereas others are spared. Current evidence suggests that variations on the total amount of alcohol consumed and genetic variations in specific pathways may contribute to the multifaceted clinical presentations of alcoholism. Because alcohol is the single most common drug ingested by patients, common interactions of drugs that have dental significance should be suspect. Most commonly, these interactions involve anesthetic agents and sedative hypnotic drugs. Dental specialists may encounter alcoholic persons in intoxicated, withdrawing, or rehabilitating states. In any of these phases, appropriate recognition and judicious support of the dental problems will contribute to the overall well-being of these persons.