DIFFERENCES IN HLA-DR ASSOCIATION WITH RHEUMATOID ARTHRITIS AMONG MIGRANT INDIAN COMMUNITIES IN SOUTH AFRICA

Previous surveys among Indians with RA have shown a significantassociation with HLA DR4 in North India and with HLA DR1 inthe UK. We studied a migrant Indian population in South Africato determine their genetic associations with RA. A group of121 unrelated RA patients from three communities (Hindi, Muslimsand Tamils) were studied. The Muslims showed a significant associationwith DR4 but the Hindi and Tamils showed a significant associationwith DR10. This survey shows that the Indian community is aheterogenous group regarding their HLA associations with RAand different associations are noted in the various communities. KEY WORDS: Rheumatoid arthritis, HLA antigens, Indians, Ethnic groups     

Efficacy of a nicotine nasal spray in smoking cessation: a placebo-controlled, double-blind trial

Laboratory trials have demonstrated the efficacy of nicotine replacement in smoking cessation bur absolute success races are low. For many, nicotine gum is hard to use and transdermal nicotine is slow-acting and passive. A new, faster-acting nicotine nasal spray (NNS) can provide easily self-administered relief from cigarette withdrawal. The NNS was tested for safely and efficacy in smoking cessation. Two hundred and fifty-five smokers were randomized to NNS or a piperine placebo. Drug use was limited to 8–32 doses/day for 6 months. Subjects were tested while smoking and at post-cessation daily (week 1) with follow-up at weeks 2, 3, 6 and at 3 months, 6 months and 1 year. Continuous abstinence analyses (CO ≤8 ppm.; no slips) showed that NNS significantly enhanced success rates over placebo overall (p < 0.001) and at all test intervals. Differences at key intervals between active and placebo were: 63% vs. 40% (day 5), 51% vs. 30% (week 3), 43% vs. 20% (6 weeks), 34% vs. 13% (3 months), 25% vs. 10% (6 months) and 18% vs. 8% (1 year). Side effects were common but tolerable. Cotinine measures showed that replacement of nicotine approximated 30% of smoking levels. Hazard functions revealed relapse risks peaked at day 1, day 5 and 3 weeks for strict abstinence. It is concluded NNS is safe, efficacious and a viable alternative treatment for smoking cessation.     

Mutations in GCK and HNF-1alpha explain the majority of cases with clinical diagnosis of MODY in Spain

OBJECTIVE: The aim of this study was to group patients with MODY (maturity-onset diabetes of the young) according to the genetic alterations underlying the disease and to investigate their clinical characteristics. PATIENTS AND METHODS: Molecular analysis of GCK (MODY2), HNF-1alpha (MODY3), HNF-4alpha (MODY1) and HNF-1beta (MODY5) genes was performed by DNA sequencing in 95 unrelated index probands (47M/48F; mean age 9.9 +/- 5.2 years) with clinical diagnosis of MODY. After classification into MODY subtypes according to the genetic alterations, clinical characteristics were compared between the groups. RESULTS: Seventy-six families were shown to carry mutations in GCK (34 of them previously unreported), eight families presented HNF-1alpha mutations, and a large genomic rearrangement in HNF-1beta was found in a family. No alteration was found in HNF-4alpha. Thus, relative frequencies in the group studied were 80% MODY2, 8.5% MODY3 and 1% MODY5. Comparison of clinical parameters according to genetic status showed significant differences between MODY2 and MODY3 patients in age at diagnosis (9.4 +/- 5.4 years vs. 12.7 +/- 4.6 years), diagnosis (impaired glucose tolerance vs. diabetes), diagnostic test used (OGTT vs. fasting glucose), treatment (diet and exercise vs. insulin/oral antidiabetic agents) and birth weight (2.96 +/- 0.44 kg vs. 3.40 +/- 0.67 kg). CONCLUSION: Almost 90% of the MODY cases in the group studied are explained by mutations in the major genes GCK (MODY2) and HNF-1alpha(MODY3), although differences in the relative prevalence of each form could be partly due to patient referral bias (paediatric vs. adult). In general, patients with MODY2 were diagnosed at an earlier age in life than MODY3 patients and had a milder form of diabetes. Moreover, the majority of patients with MODY2 mutations were treated with diet whereas half of MODY3 patients received pharmacological treatment.     

THE PREVALENCE OF DIFFUSE IDOIOPATHIC SKELETAL HYPEROSTOSIS IN AFRICAN BLACKS

The prevalence of diffuse idiopathic skeletal hyperostosis (DISH)was studied in a hospital based population of African Blacksover the age of 40 years. The study was based on an analysisof the lateral chest radiographs of 1000 patients in a retrospectivestudy and 500 consecutive medical admissions in a prospectivestudy. The overall prevalence of DISH was 3.9% (males 3.8% andfemales 4.2%). There was a rise in the prevalence of DISH withincreasing age from 1% in the 40–49 year age group to13.6% in those over 70 years. The prevalence of diabetes was52.4% in the 21 patients with DISH who were seen in the prospectiveanalysis. Ankylosing spondylitis, which is associated ith HLA-B27,is rare in African Blacks. However, DISH is not uncommon butits prevalence is lower than in a similar hospital based studyof Jews in Israel. KEY WORDS: Spine, Ageing, Race, Diabetes, Prevalence     

The Heart in Rheumatoid Arthritis -a Clinical and Echocardiographic Study

A clinical and echocardiographic study was casrried out in arandomly selected group of 101 patients with rheumatoid arthritisto determine the prevalence of cardiae abnormalities. Adequatetwo-dimensional assessments were obtained in 84 patients and77 patients had adequate M mode recordings. Thirty-one patients(37 per cent) had 45 echocardiographic abnormalities. Five patients(6 per cent) had a pericardial effusion. Eleven abnormalitiesof the mitral valve were noted in 10 patients (13 per cent).Three patients had mitral valve prolapse, one patient with aorticincompetence had flutter on the mitral valve, five patientshad mitral annular calcium and one patient had hypertrophicobstructive cardiomyopathy and mitral annular calcification.A reduction in the E-F slope was noted in 12 patients, sevenof whom had associated cardiac disease, one patient had a sinustachycardia and four patients (5 per cent) had a mild reductionwithout any other cardiac abnormality. Apart from the presenceof pericardial effusion in 6 per cent and minor abnormalitiesof the E-F slope in 5 per cent of patients, all the other significantechocardiograp hic abnormalities could be related to the presenceof associated cardiac disease.     

N-Acetylcysteine Added to Volume Expansion with Sodium Bicarbonate Does Not Further Prevent Contrast-Induced Nephropathy: Results from the Cardiac Angiography in Renally Impaired Patients Study

We reviewed data from the multicenter CARE (Cardiac Angiography in Renally Impaired Patients) study to see if benefit could be shown for N -acetylcysteine (NAC) in patients undergoing cardiac angiography who all received intravenous bicarbonate fluid expansion. Four hundred fourteen patients with moderate-to-severe chronic kidney disease were randomized to receive intra-arterial administration of iopamidol-370 or iodixanol-320. All patients were prehydrated with isotonic sodium bicarbonate solution. Each site chose whether or not to administer NAC 1,200 mg twice daily to all patients. Serum creatinine (SCr) levels and estimated glomerular filtration rate were assessed at baseline and 2–5 days after receiving contrast. The primary outcome was a postdose SCr increase 0.5 mg/dL (44.2 μmol/L) over baseline. Secondary outcomes were a postdose SCr increase 25% and the mean peak change in SCr. The NAC group received significantly less hydration (892 ± 236 mL vs. 1016 ± 328 mL; P < 0.001) and more contrast volume (146 ± 74 mL vs. 127 ± 71 mL; P = 0.009) compared with no-NAC group. SCr increases 0.5 mg/dL occurred in 4.2% (7 of 168 patients) in NAC group and 6.5% (16 of 246 patients) in no-NAC group (P = 0.38); rates of SCr increases 25% were 11.9% and 10.6%, respectively (P = 0.75); mean post-SCr increases were 0.07 mg/dL in NAC group versus 0.11 mg/dL in no-NAC group (P = 0.14). In conclusion, addition of NAC to fluid expansion with sodium bicarbonate failed to reduce the rate of contrast-induced nephropathy (CIN) after the intra-arterial administration of iopamidol or iodixanol to high-risk patients with chronic kidney disease.