Prevalence of genetic haemochromatosis and iron overload in patients attending rheumatology and joint replacement clinics.

BACKGROUND & AIMS: Genetic Haemochromatosis (GH) is common in North European and Celtic populations and is associated with arthropathy. We aimed to measure the frequency of the common GH mutations (C282Y and H63D), the carrier frequency of C282Y and markers of iron overload in patients who were referred to our rheumatology and joint replacement clinics. METHODS: Unselected patients attending these clinics were anonymously tested for the described mutations. Transferrin saturation and serum ferritin were also measured and if elevated, the patients had predictive counselling then named GH mutation testing. The carrier and mutation frequencies were also determined in 340 local controls. RESULTS: One hundred and sixty-one unselected patients attending these clinics were studied. The C282Y mutation carrier frequency was 1 in 5.2 in patients compared with 1 in 8.1 in controls (p < 0.005). The overall mutation frequencies were similar in patients and controls. One patient was found to be a homozygous for the C282Y mutation and eight were compound heterozygotes. Seven other patients had a raised ferritin, one of whom was a C282Y heterozygote. CONCLUSION: The C282Y carrier frequency is significantly higher in patients attending rheumatology and joint replacement clinics than in controls. Screening of these patients for GH should be considered.

Effect of vitamin E supplementation on oxidative stress in hemodialysis patients.

Hemodialysis represents a chronic stress status for its recipients. Many hypotheses state that this may be associated with oxidative stress. Thus, there may be deficiency of antioxidants like erythrocytic superoxide dismutase, catalase, vitamin E or increased generation of free radicals like superoxide anions. A study was carried out to investigate oxidant and antioxidant status in chronic renal failure patients undergoing hemodialysis and effect of vitamin E supplementation on these two status. Blood samples were collected from patients before and after hemodialysis and from controls. The samples were analyzed for quantitation of MDA as index of lipid peroxide, nitric oxide, vitamin E, vitamin C and enzymatic antioxidants namely erythrocyte SOD and catalase. As compared to controls, the levels of serum MDA were significantly increased and activities of erythrocyte SOD and catalase, levels of serum nitric oxide, serum vitamin E and plasma vitamin C were significantly decreased both before and after hemodialysis. The efficiency of vitamin E therapy in hemodialysis patients was assessed by re-evaluating oxidant and antioxidant status of same patients after supplementation of vitamin E. Vitamin E supplementation caused decrease in serum MDA and increase in levels of serum nitric oxide, vitamin E, vitamin C and activities of erythrocytic SOD and catalase. Our results suggest the presence of oxidative stress and the possible preventive role of vitamin E therapy in hemodialysis patients.

Oxidative stress and disturbance in antioxidant balance in beta thalassemia major.

Repeated blood transfusion in beta thalassemia major patients may lead to peroxidative tissue injury by secondary iron overload. In the present study, 72 children with beta thalassemia major were included. Serum levels of total lipid peroxides, Iron, Total Iron Binding Capacity, Copper, Zinc, Vitamin E, plasma Total Antioxidant Capacity, activity of Erythrocyte Superoxide Dismutase, were measured. The findings were compared with 72 age matched healthy controls irrespective of sex. A significant increase in the levels of lipid peroxide and Iron (p<0.001), whereas, significant decrease in the levels of vitamin-E, Total Antioxidant Capacity and Total Iron Binding Capacity (p<0.001) was observed. Serum Zinc was significantly increased (p<0.001) with significant decrease in the levels of copper (p<0.001). Non Significant increase in the activity of Erythrocyte Superoxide Dismutase (p>0.05) was found in the patients when compared with controls. This suggest that oxidative stress and reduced antioxidant defense mechanism play an important role in pathogenesis of beta thalassemia major.

Tissue concentration, systemic distribution and toxicity of clofazimine--an autopsy study.

There are very few autopsy studies available on systemic distribution of clofazimine, a drug with anti-mycobacterial activity, used in multidrug therapy (MDT) regimen of leprosy and in erythema nodosum leprosum (ENL). An autopsy study was done on a 45 year old female of lepromatous leprosy (LL) on MDT and long term high dosage of clofazimine. Patient succumbed to intractable abdominal pain, diarrhoea, hypokalemia following clofazimine treatment. Autopsy study revealed yellowish brown discoloration of skin, viscera and body fluids. Chemical extraction of the drug revealed the highest concentration of the drug in jejunum (1.5mg/gm),followed by spleen (1.2mg/gm), pancreas (0.4mg/gm), adrenal (0.25mg/gm), liver (0.21mg/gm), and less than 0.2mg/gm in lung, fat, large intestine and stomach. It can be inferred from the present study that the drug is absorbed from the jejunum and gets deposited in fat, reticulo-endothelial cells (R-E cells) and hepatocytes. The drug is best demonstrated in cryostat sections and is lost partly during tissue processing and staining. The drug toxicity can be fatal as seen in the present case.