Expression of the matrix metalloproteinases MMP-2 and MMP-9 and their inhibitors TIMP-1 and TIMP-2 in systemic lupus erythematosus patients.

BACKGROUND: The study aimed to look at alterations in expression of matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) and their potential use as biomarkers in the pathogensis of SLE. METHODS: SLE patients (n = 41) and healthy controls (n = 50) were recruited. Quantitative RT-PCR/ELISA assays were performed for expression of MMP and TIMP mRNA in whole blood and PBMC; and corresponding serum protein levels. Intracellular levels of MMP-2 and MMP-9 proteins were analysed by flow cytometry. RESULTS: Based on SLEDAI scores patients were grouped into active (SLEDAI ≥ 10) and inactive cases (SLEDAI < 10). In active cases, MMP-2 expression significantly increased and TIMP-2 expression was decreased (p < 0.0001) both at serum secretion (p = 0.0003) and mRNA (p < 0.0001) levels as compared to inactive cases. MMP-9 and TIMP-1 showed significantly reduced serum secretion and mRNA expression (p < 0.0001) in active cases as compared to inactive cases. Intracellular concentration of MMP-9 was reported to be higher in neutrophils, while MMP-2 was mainly found in lymphocytes of SLE patients as compared to controls. MMP/TIMP ratio profile was altered as SLE disease progresses. INTERPRETATION & CONCLUSIONS: Findings suggest disturbed MMP and TIMP levels have a role in the pathogenesis of SLE.

Role of MMP-7 in the pathogenesis of systemic lupus erythematosus (SLE).

Systemic lupus erythematosus (SLE) is a clinically heterogeneous chronic, inflammatory autoimmune disorder. The association of MMP-7 and disease severity is still unclear. A total of 150 SLE patients and matched healthy controls were recruited for this study. Disease activity was scored according to SLEDAI (98 active and 52 inactive disease). Mean serum MMP-7 levels were significantly higher in SLE patients than controls ( p < 0.001). Patients with active disease showed higher levels (16.24 ± 6.2 ng/ml) as against inactive disease (10.50 ± 3.97 ng/ml) ( p ≤ 0.0001). Mean MMP-7 mRNA expression was significantly higher in patients (RQ = 3.16 ± 0.93) as compared to controls (RQ = 2.21 ± 0.89, p = 0.006). A positive correlation between MMP-7 levels, mRNA expression and SLEDAI score was observed ( r = 0.563, r = 0.427). The MMP-7 -181 G allele was found to be significantly higher among SLE patients ( p < 0.0001). A significant association was noted between MMP-7 -181 A/G +G/G genotypes with renal ( p = 0.0027) and CNS ( p = 0.0031) manifestations and anti-dsDNA autoantibodies ( p = 0.0312). Serum MMP-7 levels and mRNA expression were elevated in advanced stages of SLE, indicating that MMP-7 is associated with disease activity in SLE.

Do high sensitivity C-reactive protein and serum interleukin-6 levels correlate with disease activity in systemic lupus erythematosuspatients?

INTRODUCTION: Systemic Lupus Erythematosus (SLE) is an inflammatory autoimmune disease where an interplay between acute phase proteins and cytokines are involved in disease activation. AIM AND OBJECTIVES: This case control study was performed to investigate interrelationship between high sensitivity C-reactive proteins (hs-CRP), Interleukin-6 (IL-6) levels and disease activity among SLE patients. MATERIALS AND METHODS: One hundred forty one clinically diagnosed SLE cases were included and disease activity was noted by SLE Disease Activity Index (SLEDAI). Serum IL-6 levels were measure by cytokine multiplex assay. Serum hs-CRP, C3 and C4 levels were measure by nephelometer. The Pearson correlation test was used for correlation between hs-CRP, Il-6 and SLEDAI. RESULTS: Based on SLEDAI, 126 patients (89.4 %) had active disease and 15 patients (10.6%) had inactive disease. Mean hs-CRP levels in SLE patients were significantly higher (12.1+ 11.5 mg/L) than controls (2.41+ 1.37 mg/L) (P < 0.0001). Hs-CRP levels among active SLE were significantly higher (13.5+ 11.4 mg/L) as compared with inactive SLE (4.4 + 2.9 mg/L) (P=0.0002). Similarly, IL-6 levels in SLE patients were significantly higher among active SLE (26.9 + 15.5 pg/ml) as compared with inactive SLE (13.9+ 10.2 pg/ml) (P=0.0001). An inverse correlation between Il-6 and hemoglobin levels between active and inactive SLE was noted (r=-0.46, P <0.0001). CONCLUSION: This study suggests a good correlation between hs-CRP, IL-6 and SLE disease activity indicating their direct involvement in inflammatory conditions associated with disease.

Ebola Virus: Another Challenge from the Deadly Viral Brigade.

Ebola viruses are the causative agents of a severe form of viral haemorrhagic fever in man, designated Ebola haemorrhagic fever, and are endemic in regions of central Africa. The recent west African outbreak of Ebolavirus has brought this filoviral infection again in limelight, Indian government has issued guidelines to various airports to screen travelers coming from Africa and middle east Haj pilgrims to keep a check on this highly virulent infection. This viral hemorrhagic disease has remained confined majorly to Africa but its high outbreak potential makes it essential for all infectious disease clinicians and people dealing with travel medicine to be cautious. Management of these patients with symptomatic therapy is the current strategy which is followed. There is absence of any effective vaccine so further research is warranted in this direction.

Assessment of use of complementary alternative medicine and its impact on quality of life in the patients attending rheumatology clinic, in a tertiary care centre in India.

PURPOSE: Complementary and alternative medicine (CAM) has witnessed an increase in use in recent times in rheumatological conditions and is expected to have impact on the quality of life (QOL). We had planned to conduct this study to investigate the extent of use of CAM and its effect on QOL of patients at a tertiary care center. MATERIALS AND METHODS: Ethics committee approval was obtained. Sixty patients suffering from osteoarthritis (OA) and rheumatoid arthritis (RA) were enrolled as per the selection criteria, after obtaining their informed consent. Each patient was interviewed for CAM use/non-use, and Western Ontario and McMaster Universities (WOMAC) (modified) index for QOL was recorded by the study personnel. STATISTICAL ANALYSIS: The normality was checked by using Kolmogorov-Smirnov test. Descriptive statistics was performed and Mann-Whitney U-test was used to compare the QOL of CAM users and non-users. RESULTS: Of the 60 patients enrolled with OA (10) and RA (50), 58% (35/60) used CAM. Ayurveda and massage therapy were the commonest [80% (28/35)], followed by yoga asana [34% (12/35)] and homoeopathy [20% (7/35)]. It was observed that combinations of therapies were used too. Nearly half [49% (17/35)] of the CAM users were on self-prescribed medication and 71% (25/35) of them did not inform the physician of CAM use. The QOL of CAM users (WOMAC score: 56.31 ± 6.82) was better than that of CAM non-users (WOMAC score: 60.16 ± 4.02) (P value 0.01). CONCLUSION: Patients with RA frequently used CAM and QOL improvised with CAM use. We observed that self-administration of CAM was common and this was not informed to the treating physician.

Tumefactive demyelination.

We present a case of 22 year old female who had pulmonary tuberculosis followed by tuberculous meningitis and tuberculomas in past. This time she presented to us with right hemiparesis and altered sensorium. Diagnosis of tumefactive demyelination was made on the basis of typical MRI findings. Patient showed good response to steroids.

Serum uric acid in acute myocardial infarction.

BACKGROUND: There is evidence that high uric acid is a negative prognostic factor in patients with mild to severe heart failure. A study showed a close correlation between serum uric acid concentration and Killip classification in patients of acute myocardial infarction. MATERIAL AND METHODS: We studied 100 patients with acute myocardial infarction and 50 controls. Serum uric acid level was measured on day 0, 3 & 7 of MI. RESULTS: There was a statistically significant higher level of serum uric acid concentration in patients of MI on day of admission as compared to controls. Patients with history of MI in the past had higher serum uric acid levels. On all the days serum uric acid levels were higher in patients who were in higher Killip class. All the five patients who died after 3 days of hospital stay had serum uric acid level more than 7.0 gm/dL and all of them were Killip class IV. CONCLUSIONS: Serum uric acid levels are higher in patients of acute myocardial infarction correlated with Killip class. Combination of Killip class and serum uric acid level after acute myocardial infarction is a good predictor of mortality after AMI.

Cardiac amyloidosis.

We present a 54 year old male who presented with congestive cardiac failure and was diagnosed as restrictive cardiomyopathy with mild mitral regurgitation on 2D echocardiography. Cardiac amyloidosis was diagnosed in view of renal biopsy revealing amyloid deposition. Patient did not have any obvious etiology for secondary amyloidosis.

Evaluation of efficacy and tolerability of dothiepin hydrochloride in the management of major depression in patients suffering from rheumatoid arthritis.

Several studies have shown that 20 to 66.2% of patients with rheumatoid arthritis have associated psychiatric comorbidity especially depression. Dothiepin hydrochloride is a well-established and effective antidepressant in patients with depressive symptoms of varying severity and co-existing anxiety. To document the efficacy and tolerability of dothiepin hydrochloride in the management of major depressive disorder (MDD) in rheumatoid arthritis patients a phase IV, open, single arm, prospective study was initiated with dothiepin hydrochloride in the dose of 75 mg/day, duration of therapy was 6 weeks. Twenty-five rheumatoid arthritis patients suffering from co-morbid MDD completed the 6-week dothiepin hydrochoride treatment and were considered for final analysis. There was significant reduction (p < 0.05) in mean HAM-D scores at week 2 (13.92 +/- 5.45), week 4 (9.28 +/- 4.13) and week 6 (5.72 +/- 3.26) compared to baseline (21.64 +/- 5.93). There was significant reduction (p < 0.05) in mean HAM-A scores at week 2 (6.52 +/- 3.34), week 4 (4.0 +/- 2.25) and week 6 (2.76 +/- 1.59) compared to baseline (10.68 +/- 3.68). The global impression of efficacy at the end of 6 weeks of dothiepin hydrochloride treatment was rated by the clinician (psychiatrist) as marked and moderate improvement in 20 (80%) and 5 patients (20%) respectively. Only 2 patients reported dry mouth as an adverse event in the study. The overall assessment of tolerability at the end of 6 weeks of dothiepin hydrochloride treatment was rated by the clinician (psychiatrist) as good and fair in 19 (76%) and 6 patients (24%) respectively. Dothiepin hydrochloride was found to be an effective and well-tolerated drug in the management of MDD and anxiety in patients suffering from rheumatoid arthritis.

Biphasic demyelination of the nervous system following anti-rabies vaccination.

Acute disseminated encephalomyelitis (ADEM) is an acute or subacute condition characterized by widespread multifocal neurological deficits of variable severity. We report a case of a 45-year-old man with ADEM following anti-rabies vaccine (ARV).

Idiopathic hypereosinophilic syndrome manifesting as pulmonary oedema.

Idiopathic hypereosinophilic syndrome is a progressive and fatal disease if not treated effectively. We report this case since hypereosinophilia is an uncommon cause of pulmonary oedema.

Neuropathy in rheumatoid arthritis.

BACKGROUND: Paucity of Indian literature on rheumatoid neuropathy creates a lacuna in the critical evaluation and discussion of the subject. We did this study to find out the incidence and pattern of neuropathy and to correlate it with disease parameters and other extra-articular involvement. MATERIAL AND METHODS: We studied 31 patients of rheumatoid arthritis (RA) classified by ACR criteria. Electromyography and nerve conduction studies (EMG/NCV) were done in all the patients apart from routine laboratory and radiological investigations. Electrocardiograph (ECG), pulmonary function tests (PFT) and ophthalmological examination were also carried out to ascertain extra-articular involvement. RESULTS: Ten out of 31 RA patients had neuropathy of which five each were overt and subclinical respectively. Only one patient had entrapment neuropathy. Four of the ten patients had pure motor neuropathy whereas the other six were sensori-motor neuropathies. Four patients had mononeuritis multiplex and five had symmetrical peripheral neuropathy. Nine of the ten neuropathic patients had RA for more than 2 years. Seven patients had other extra-articular features along with neuropathy. CONCLUSIONS: One-third of patients with RA have evidence of neuropathy. Disease parameters such as activity, rheumatoid factor and functional and radiological grade do not correlate with neuropathy. Non-entrapment sensori-motor type of neuropathy is the most common type.

Relationship between osteoarthritis of knee and menopause.

AIM: To study the difference in the onset of osteoarthritis (OA) between males and females with respect to age and to note the relationship between OA of the knees and menopause and hysterectomy in females. MATERIAL AND METHODS: One hundred consecutive patients (50 males and 50 females) were studied for the onset of OA and compared for the statistical difference. In females the relationship between onset of OA and menopause and hysterectomy, if done, was noted. RESULTS: Fifty eight percent of females had onset of symptoms of OA of knees before 50 years of age as compared to only 20% in males (p < 0.05). Sixty four percent of females with OA of knees had the onset of symptoms either perimenopausally or within five years of natural menopause or hysterectomy. CONCLUSION: There is a definite early peaking of the incidence of OA of knees in women in the fifth decade of life as compared to males. There is an association between OA of knees and menopause and we suggest correlating it with the levels of sex hormones.

Leprosy: a close mimic in a rheumatology clinic.

Cutaneous and neurological manifestations of leprosy are readily diagnosed. However, physicians sometimes fail to recognize that leprosy may present with a rheumatic symptoms. A plethora of rheumatic manifestations are associated with leprosy, particularly with lepra reactions. A diligent examination for skin lesions/nerve involvement may uncover the diagnosis of leprosy in a patient referred for a rheumatological disorder. To highlight the fact that leprosy can mimic several rheumatological disorders, we have discussed a few representative cases seen over the past two years at our rheumatology clinic in a teaching hospital. In all these cases, a diagnosis of leprosy was made when the patient was referred for a rheumatic complaint.