Factors associated with silent myocardial ischemia,autonomic or peripheral neuropathies,and survival in diabetes mellitus type 2 patients without cardiovascular symptoms

International Journal of Diabetes in Developing Countries - Complications from diabetes mellitus (DM) include cardiovascular system, peripheral neuropathy (PN), and autonomic dysfunction (AD)....     

Novel genetic markers of rheumatoid arthritis in chilean patients,by dr serotyping and restriction fragment length polymorphism analysis

Objective. The analysis of genetic markers of rheumatoid arthritis (RA) in a population in which the DR4 serotype is not strongly associated with the disease. Methods. Chilean RA patients (56 seropositive and 22 seronegative) and 141 controls were studied by serotyping. Southern blot analysis of Bam HI restriction fragment length polymorphism (RFLP) was done in genomic DNA from 46 patients with seropositive RA, 17 patients with seronegative RA, and 45 controls, using a complementary DNA probe specific for DRB1 genes. Results. The prevalence of the HLA—DR9 haplotype was strikingly higher in seropositive RA patients (21%) than in controls (3%) (P_corr < 0.0008, by Fisher's exact test; relative risk [RR] = 9.34). The prevalence of DR4 and DR1 haplotypes, although slightly increased, did not achieve a significant preponderance. The simultaneous presence of two Bam HI fragments (3.6 kb and 4.5 kb) was found with higher prevalence in seropositive patients (83%; RR = 9; P_corr < 0.00002) than in controls (36%), and seemed higher in seronegative RA patients as well (71%; RR = 4). Furthermore, its prevalence remained increased in comparisons of DR4 positive controls (36%) with DR4 positive seropositive patients (100%; RR = 67; P_corr < 0.0002) and DR4 positive seronegative patients (100%; RR = 36; P_corr < 0.006), even after excluding the DR9 positive individuals. A tendency toward higher association with DR1 seropositive RA patients (67%; RR = 12), a group with no DR4 or DR9 positive individuals, than in DR1 positive controls (14%), was also observed. Conclusion. The HLA—DR9 haplotype was definitively consolidated as a very strong genetic marker exclusively for seropositive RA in Chilean patients, as suggested by our previous observations. RFLP analysis showed that the simultaneous presence of 3.6-kb and 4.5-kb Bam HI fragments constituted a better RA marker than did any of the heretofore studied haplotypes. These fragments together would be linked to RA independently of the DR1, DR4, and DR9 haplotypes. The overall evidence indicates that Chilean seropositive RA patients display a genetic background that is different from that underlying RA susceptibility in other populations and suggests the existence of common, as well as distinct, genetic elements predisposing to seronegative and seropositive RA.     

Motion correction and myocardial perfusion SPECT using manufacturer provided software. Does it affect image interpretation?

Purpose  

Myocardial perfusion SPECT is an excellent tool for the assessment of coronary artery disease (CAD); however, it is affected by several artifacts, such as patient motion during acquisition, which increases false-positive rates. Therefore, the purpose of this work is to analyze changes in perfusion scores after motion-correction software application.     

The presence of the HLA-DRB1 shared epitope correlates with erosive disease in Chilean patients with rheumatoid arthritis

OBJECTIVE: To assess the contribution of the HLA-DRB1 shared epitope (SE) to the radiological outcome of rheumatoid arthritis (RA) after 6 yr of follow-up in a reported series of 129 Chilean patients with established disease. METHODS: A prospective study was conducted between 1992 and 1998 using hand radiographs to assess disease outcome in a published series of patients in whom two doses of the SE were present in 20%, one dose was present in 34% and the SE was absent in 46%. At study entry, 29 of the 92 patients with hand radiographs were at Steinbrocker stages I or II (non-erosive), with a median disease duration of 2.8 yr (0.4-17). RESULTS: In 1998, 113 (87%) of the patients were alive. One hundred and eight patients underwent complete clinical evaluation. Their median age was 57 yr (range 30-81) and the median disease duration was 15 yr (6-50). We were able to study 25 of the 29 patients who had non-erosive disease at study entry in 1992. We found that 10 of 11 patients having one or two doses of the SE developed erosive disease compared with three of 14 without the SE (Yates' corrected P=0.0023, relative risk 4.24, 95% confidence interval 1.53-11.77). CONCLUSIONS: These observations support and extend the notion that the presence of the SE in one or two doses can predict the development of erosions even in RA populations in whom the SE is not as prevalent as in Caucasians.     

Insulin-like growth factor I (IGF-I), IGF-binding proteins, and breast cancer.

Epidemiological evidence supports a role for the insulin-like growth factors (IGFs) and their binding proteins (IGFBPs) in the induction and progression of various cancers. Estrogen, which plays a role in the etiology of breast cancer, both regulates and is influenced by the IGF family. Risk of breast cancer associated with serum levels of IGF-I and/or IGFBPs may therefore depend upon menopausal status. A nested, case-control study was conducted on 66 women who were premenopausal and 60 who were postmenopausal at the time of diagnosis of primary breast cancer; they were selected from a cohort of 95,000 women who underwent multiphasic health check-ups > 30 years ago when enrolled in the Kaiser Permanente Medical Care Program. For each case, one control who matched by age, date of examination, and length of follow-up was chosen. Concentrations of IGF-I, insulin, glucose, and IGFBP-1, IGFBP-2, and IGFBP-3 in serum drawn at least 2 years before diagnosis (mean times of 10.5 and 15.8 years for pre- and postmenopausal cases, respectively) were compared using conditional logistic regression analysis. All statistical tests were two-sided. Serum IGF-I, adjusted for insulin, glucose, and body mass index, was weakly associated with breast cancer risk across quartiles for premenopausal women only (P for trend = 0.05). Serum IGFBP-3 was higher in premenopausal cases versus controls (P = 0.04) and showed a positive trend in risk for increasing quartiles (P for trend = 0.033). After adjusting for insulin, glucose, body mass index, and IGF-I, premenopausal women in the highest quartile of IGFBP-3 had an elevated risk of breast cancer [odds ratio (OR) = 5.28, 95% confidence interval (CI) = 1.13-24.7]. Conversely, IGFBP-3 was lower in postmenopausal cases versus controls (P = 0.04) but showed no significant trend in risk. Postmenopausal women with glucose levels in the diabetic range were at increased risk for developing breast cancer (OR = 2.06, 95% CI = 0.87-4.91), whereas those in the highest quartile of IGFBP-2 had a substantial reduction (71%) in risk relative to those in the lowest quartile (OR = 0.29, 95% CI = 0.09-0.92). Serum IGFBP-1 was not associated with breast cancer risk in either pre- or postmenopausal women. In premenopausal women, elevated serum IGF-I and IGFBP-3 are associated with increased breast cancer risk, whereas elevated serum IGFBP-2 is inversely associated with risk of postmenopausal breast cancer.     

Is the addition of ECG gating to technetium-99m sestamibi SPET of value in the assessment of myocardial viability?

The main goal of this study was to evaluate whether the addition of ECG gating to technetium-99m sestamibi single-photon emission tomography (SPET) perfusion imaging assists the prediction of recovery of regional wall motion abnormalities after revascularization. Thirty-six patients with coronary artery disease were included in the study. All had wall motion abnormalities, and 31 (86%) had a clinical history of myocardial infarction. Coronary artery bypass surgery was performed in 18 patients and angioplasty in the remainder. All underwent ECG-gated and non-gated SPET at rest and after intravenous dipyridamole. Two-dimensional echocardiography was performed at a mean of 27 days before revascularization and at a mean of 69 days following revascularization to assess segmental wall motion changes. Perfusion prior to revascularization was analysed qualitatively and quantitatively on gated and non-gated SPET, and the results compared with those of echocardiography. Bullseye parameters were obtained from a normal database, generated from data in 40 normal volunteers, using dipyridamole ECG-gated and non-gated sestamibi SPET. There was good concordance between gated and non-gated qualitative analysis (79% with kappa=0.65) for normal, viable or necrotic segments. Gated SPET predicted functional recovery in 27 of 35 (77%) segments showing echocardiographic improvement while non-gated SPET did so in 30 of 39 (77%) such segments. Gated SPET predicted no functional recovery in 20 of 45 (44%) segments that did not show improved wall motion after revascularization, while with non-gated SPET the figure was 18 of 51 (35%). The positive predictive values of gated and non-gated SPET with regard to the recovery of wall motion following revascularization were 52% and 48%, while the negative predictive values were 71% and 67%, respectively.^99mTc-sestamibi had a low predictive value for recovery of function if visual assessment was used in the analysis of SPET data. Quantitative bullseye sestamibi parameters (defect extension and severity, reversibility and percentage change in extension), from gated or non-gated studies, appear best to distinguish which segments will display improved motility on the echocardiogram after revascularization. The addition of ECG gating does not significantly increase the predictive value of SPET imaging with regard to recovery of function.     

A population based assessment of the use of orthopedic surgery in patients with rheumatoid arthritis

OBJECTIVE: To describe the use of orthopedic surgery, including joint replacement surgery, in a well defined population based cohort of patients with rheumatoid arthritis (RA) and to identify characteristics that predict such use. METHODS: A retrospective medical record review was performed of cases of RA incident in Rochester, MN, during the years 1955-85. Patients were followed until 1998. All joint surgeries were recorded, including joint reconstructive surgeries, total joint arthroplasty (TJA), and other joint reconstructive procedures (JRP) such as tendon transfers and resections, joint fusions, and surgeries for fractures and infections involving joints. RESULTS: Of the total 424 RA incident cases, 148 (34.9%) patients underwent one or more (maximum of 20/patient) surgical procedures involving joints during their followup (median 14.8 yrs, range 0.2-42.8 yrs). Overall, this RA cohort had 9.7 surgeries per 100 person-yrs of followup. The estimated cumulative incidence of surgical procedures for RA at 30 yrs was 52.7% +/- SE 4.2. Surgeries for arthritis related joint disease of RA included: primary TJA 76 patients (31.3 +/- 4.1); JRP joint fusion 78 patients (29.4 +/- 3.5); JRP soft tissue 92 patients (29.8 +/- 3.3); and cervical spine fusion one patient. Non-RA (trauma and other) joint surgeries included TJA 26 patients (13.5 +/- 3.4) and arthrotomy for septic arthritis 8 patients (2.4 +/- 0.9). Based on Cox proportional hazards regression, the risk of having a disease related joint surgery for RA is increased in patients who are younger (p < 0.001), have positive rheumatoid factor (p = 0.01), and those with rheumatoid nodules (p < 0.001). There was a borderline significant increase in the risk of first joint surgery in women (p = 0.09). Women also had significantly more joint surgeries (11.5/100 person-yrs) than men (4.9/100 person-yrs; p < 0.001). Survival of patients who had surgery for RA related joint disease was similar to those who did not. CONCLUSION: This is the first population based assessment of joint surgeries performed in patients with RA. Reconstructive surgeries were common, and women had significantly more surgeries than men. Survivorship among patients with RA undergoing surgeries was similar to that of the RA patient population at large.     

Osteoarthritis of the knee joint: an eight year prospective study.

Thirty one patients (25 women, six men, mean age 71.7 years) with established osteoarthritis (OA) of the knee were examined clinically and radiologically on two occasions, eight years apart. Four patients thought they had got better, two of whom had striking functional improvement. Seven remained the same and 20 patients got worse, two needing knee surgery and many developing severe disabilities. Most of the patients had a history of slow acquisition of OA at new joint sites, hand disease emerging as the commonest other site of involvement. Changes in symptoms, disability, and radiographs did not correlate. Three of the four patients who improved symptomatically lost range of motion at the knee and developed more severe changes on their radiographs. Chondrocalcinosis of the knee was seen in five patients, including two of those who improved.     

Antimalarial treatment may have a time‐dependent effect on lupus survival: Data from a multinational Latin American inception cohort

Objective

To evaluate the beneficial effect of antimalarial treatment on lupus survival in a large, multiethnic, international longitudinal inception cohort.

Methods

Socioeconomic and demographic characteristics, clinical manifestations, classification criteria, laboratory findings, and treatment variables were examined in patients with systemic lupus erythematosus (SLE) from the Grupo Latino Americano de Estudio del Lupus Eritematoso (GLADEL) cohort. The diagnosis of SLE, according to the American College of Rheumatology criteria, was assessed within 2 years of cohort entry. Cause of death was classified as active disease, infection, cardiovascular complications, thrombosis, malignancy, or other cause. Patients were subdivided by antimalarial use, grouped according to those who had received antimalarial drugs for at least 6 consecutive months (user) and those who had received antimalarial drugs for <6 consecutive months or who had never received antimalarial drugs (nonuser).

Results

Of the 1,480 patients included in the GLADEL cohort, 1,141 (77%) were considered antimalarial users, with a mean duration of drug exposure of 48.5 months (range 6–98 months). Death occurred in 89 patients (6.0%). A lower mortality rate was observed in antimalarial users compared with nonusers (4.4% versus 11.5%; P< 0.001). Seventy patients (6.1%) had received antimalarial drugs for 6–11 months, 146 (12.8%) for 1–2 years, and 925 (81.1%) for >2 years. Mortality rates among users by duration of antimalarial treatment (per 1,000 person‐months of followup) were 3.85 (95% confidence interval [95% CI] 1.41–8.37), 2.7 (95% CI 1.41–4.76), and 0.54 (95% CI 0.37–0.77), respectively, while for nonusers, the mortality rate was 3.07 (95% CI 2.18–4.20) (P for trend < 0.001). After adjustment for potential confounders in a Cox regression model, antimalarial use was associated with a 38% reduction in the mortality rate (hazard ratio 0.62, 95% CI 0.39–0.99).

Conclusion

Antimalarial drugs were shown to have a protective effect, possibly in a time‐dependent manner, on SLE survival. These results suggest that the use of antimalarial treatment should be recommended for patients with lupus.