Tuberculosis and granuloma formation in patients receiving anti-TNF therapy.

In patients receiving anti-tumor necrosis factor (TNF) therapy, a probable exacerbation of latent tuberculosis (TB) is a major adverse event. The impairment of granuloma differentiation is considered a characteristic feature of TB in these patients. In this report we present three patients with rheumatic disease who developed TB under infliximab treatment. All of them had typical granulomas on the biopsy specimens, indicating that the expected impairment of granuloma formation is not always the case. The notion of granuloma-free TB in patients receiving anti-TNF therapy could shift a clinician's path away from performing a biopsy, thus delaying the establishment of a correct diagnosis.     

Erratum to: Depression,anxiety, and quality of life in a large cohort of patients with rheumatic diseases: common,yet undertreated

Clinical Rheumatology -     

Common variants in the gene encoding ATP-binding cassette transporter 1 in men with low HDL cholesterol levels and coronary heart disease

HDL cholesterol (HDL-C) deficiency is the most common lipid abnormality observed in patients with premature coronary heart disease (CHD). Recently, our laboratory and others demonstrated that mutations in the ATP-binding cassette transporter 1 (ABCA1) gene are responsible for Tangier disease, a rare genetic disorder characterized by severely diminished plasma HDL-C concentrations and a predisposition for CHD. To address the question of whether common variants within the coding sequence of ABCA1 may affect plasma HDL-C levels and CHD risk in the general population, we determined the frequencies of three common ABCA1 variants (G596A, A2589G and G3456C) in men participating in the Veterans Affairs Cooperative HDL Cholesterol Intervention Trial (VA-HIT), a study designed to examine the benefits of HDL raising in men having low HDL-C (< or =40 mg/dl) and established CHD, as well as in CHD-free men from the Framingham Offspring Study (FOS). Allele frequencies (%) in VA-HIT were 31, 16, and 4 for the G596A, A2589G, and G3456C variants, respectively, versus 27, 12, and 2 in FOS (P<0.03). None of the variants were significantly associated with plasma HDL-C concentrations in either population; however, in VA-HIT, the G3456C variant was associated with a significantly increased risk for CHD end points, suggesting a role for this variant in the premature CHD observed in this population.     

A phase II study of Biotene in the treatment of postradiation xerostomia in patients with head and neck cancer

 One of the major side effects of radical radiation therapy for head and neck malignancies is xerostomia, or dryness of the mouth. There is no clearly effective treatment for this condition, but we have observed that patients in our practice believe that their symptoms improve significantly when using two "over-the-counter" oral comfort products – Biotene (toothpaste, mouthwash and chewing gum) and Oralbalance gel. We decided to study these agents in a formal phase II study to evaluate their usefulness in patients with postirradiation xerostomia. Twenty-eight patients with post-irradiation xerostomia were entered on the study. All had biopsy-proven carcinoma of the nasopharynx, oropharynx, oral cavity, hypopharynx or larynx, and had received primary radiotherapy with curative intent (≥50 Gy in 20 fractions) more than 4 months before study entry. More than 75% of both parotid glands were included in the primary radiation field. There was no clinical evidence of recurrent disease. Patients were provided with a 2-month supply of Biotene mouthwash, toothpaste, chewing gum and Oralbalance gel. Response was evaluated 1 and 2 months after study entry using a patient-completed visual analogue scale to assess the severity of xerostomia and its effects on quality of life. For analysis, the scored baseline was subtracted from the later scores to assess change. Patients with an increase of 10 mm from their baseline score on the visual analogue scale were classified as having responded to the treatment intervention, and those with an increase of ≥25 mm from their baseline score were classified as having experienced a major improvement in their symptoms. After 2 months of treatment, 15 patients (54%) reported an improvement in intraoral dryness and 10 of these patients (36%) reported a major improvement. Similar proportions of patients (46% some improvement, 25% major improvement) reported an improvement in their ability to eat normally. Seventeen patients (61%) reported an improvement in oral discomfort, and 12 of these (43%) had a major improvement in their symptoms. The results of this study suggest that the use of Biotene (mouthwash, toothpaste and chewing gum) and Oralbalance gel can improve many of the symptoms of radiation-induced xerostomia. A placebo effect could account for many of the observed improvements in symptoms, and in order to assess the role of these agents in the management of patients with postirradiation xerostomia a randomised phase III study is needed. Published online: 10 March 2000     

Elevated free fatty acids and impaired adiponectin bioactivity contribute to reduced SOD2 protein in monocytes of type 2 diabetes patients

Type 2 diabetes (T2D) is characterized by increased oxidative stress contributing to the development of cardiovascular disease (CVD). Monocytes are critically important in the pathogenesis of CVD and antioxidant enzymes like superoxide dismutase (SOD2) protect these cells from excessive reactive oxygen species (ROS). Adiponectin is an adipocyte-derived protein with atheroprotective function and the effect of adiponectin on monocyte SOD2 was analyzed herein. Adiponectin upregulated SOD2 mRNA and dose- and time-dependently induced SOD2 protein in primary human monocytes. Elevated systemic free fatty acids (FFA) are commonly found in T2D patients and palmitic acid as well as oleic acid reduced monocyte SOD2 protein. Adiponectin mediated upregulation of SOD2, however, was not affected by FFA incubation. SOD2 protein was reduced in T2D monocytes compared to monocytes of age- and body mass index-matched healthy controls. Adiponectin still induced SOD2 in T2D monocytes but efficiency tended to be reduced. In summary this study indicates that elevated systemic free fatty acids and impaired adiponectin activity contribute to reduced SOD2 and most likely increased oxidative stress in T2D monocytes.     

Skoura – a genetic island for congenital insensitivity to pain and anhidrosis among Moroccan Jews, as determined by a novel mutation in the NTRK1 gene

Congenital insensitivity to pain with anhidrosis (CIPA) or hereditary sensory and autonomic neuropathy type IV is a rare, autosomal recessive neurologic disorder, characterized by absence of reaction to painful stimuli, mental retardation, self- mutilating behavior, anhidrosis, and recurrent episodes of hyperthermia. Mutations in the neurotrophic tyrosine kinase receptor 1, a receptor phosphorylated by nerve growth factor, have been documented in diverse ethnic groups. We identified the same novel nonsense mutation in two unrelated families of Moroccan Jewish descent, each with two affected siblings. This possible founder mutation may trace to the rural Jewish village in southern Morocco from where both these families originated. Genetic screening for the causative mutation among 300 unrelated Moroccan Jews did not reveal carriers for the causative mutation, thus excluding high risk for CIPA in this ethnic subpopulation.     

Predictors of impaired quality of life in patients with rheumatic diseases

Quality of life (QoL) is a complex outcome and rheumatologic patients typically exhibit several comorbidities with a negative impact. In this study, we analyzed with respect to QoL for the first time a wide range of physical and psychological factors, including individual, clinical and disease-related parameters, mental health disorders, sexual dysfunction, and cardiovascular comorbidities among consecutive rheumatologic patients. QoL was evaluated using the EuroQol 5D (EQ-5D) utility index. The Health Assessment Questionnaire (HAQ) Disability Index, and the HAQ Pain Visual Analogue Scale were used as measures of physical disability and arthritis-related pain, respectively. The Hamilton Anxiety Scale and Zung Self-Rating Depression Scale, the International Index of Erectile Function and the Female Sexual Functioning Index were completed by all patients. In total, 360 patients were included, 301 females and 59 males. In the univariate analysis, pain, physical disability (p?<?0.001 for both), disease duration (p?=?0.014), anxiety and depression (p?<?0.001 for both), as well as sexual dysfunction (p?=?0.001 for females, p?=?0.042 for males), correlated with QoL. Female sex (p?<?0.001), advanced age (p?=?0.029), lower educational level (p?=?0.005), and cardiovascular factors (hypertension, dyslipidemia, diabetes, lack of systemic exercise) also appeared to negatively affect QoL. However, in the multiple regression model, only anxiety, pain, physical disability (p?<?0.001 for all), and disease duration (p?=?0.019) remained significant predictors of QoL. The emotional side and the disease-related physiological mode of rheumatic diseases appear as major independent correlates of QoL among rheumatologic patients, who may thus benefit the most from combined supportive psychological and pain-relieving interventions.     

Prevalence of symptomatic knee, hand, and hip osteoarthritis in Greece. The ESORDIG study

OBJECTIVE: To assess the prevalence of symptomatic knee, hand, and hip osteoarthritis (OA) in the general adult population of Greece. METHODS: This cross-sectional population based study was conducted on the total adult population of 7 communities (8547 subjects) and on 2100 out of 5686 randomly selected subjects in an additional 2 communities. Sixteen rheumatologists visited the target population at their homes; an interview based on a standardized questionnaire was conducted and clinical evaluation and laboratory investigations were done, when necessary. ACR classification criteria were used for diagnosing symptomatic OA. RESULTS: Of the final target population of 10,647 subjects, 8740 (82.1%) participated in the study. The age and sex adjusted prevalence of symptomatic knee, hand, and hip OA was 6.0% (95% CI 5.6-6.4), 2% (1.8-2.2), and 0.9% (0.7-1.1), respectively. Symptomatic knee, hand, and hip OA prevalence was significantly higher among women than men and increased significantly with age. Symptomatic knee OA was significantly more common in the rural compared to urban and suburban populations. Logistic regression analysis showed a significant association of female sex and age > or = 50 years with all sites of OA, of obesity with knee and hip OA, and of a low level of education with knee OA. CONCLUSION: Symptomatic knee, hand, and hip OA is common in the general adult population of Greece, showing a female preponderance and a prevalence increasing with age. Female sex and age are risk factors for all sites of OA, obesity for knee and hip OA, and a low level of education for knee OA.