Risk factors for coronary heart disease in women with systemic lupus erythematosus: the Toronto Risk Factor Study

OBJECTIVE: Because women with systemic lupus erythematosus (SLE) are 5-8 times more likely to develop coronary heart disease (CHD) than are women in the general population, we assessed the prevalence of classic risk factors for CHD in women with SLE. METHODS: Consecutive female patients with SLE who were without evidence of CHD and were attending a large lupus clinic in Toronto were studied. The control population was recruited from among age-matched subjects attending a family practice unit for an annual physical examination. The prevalence of classic CHD risk factors and the 10-year risk of a CHD-related event were determined using the Framingham risk assessment formula. Lipid subfractions, other metabolic risk factors, lifestyle variables, and demographic characteristics were also compared between the 2 groups. RESULTS: We studied 250 SLE patients and 250 controls whose mean +/- SD age was 44.8 +/- 12 years and 44.3 +/- 15 years, respectively. Hypertension and diabetes were significantly more common among the SLE patients. Although the SLE patients had a higher mean number of CHD risk factors per patient, the 10-year risk of a CHD-related event, using the Framingham multiple risk factor assessment, was the same in SLE patients and controls (3.2%). Compared with controls, SLE patients had higher levels of very low-density lipoprotein cholesterol and total triglycerides, and had higher levels of homocysteine despite having higher folate levels. Premature menopause, sedentary lifestyle, and an at-risk body habitus were also more prevalent in SLE patients. CONCLUSION: Women with SLE have a range of detectable coronary risk factors that are not fully reflected in the Framingham risk factor formula. These factors are likely to contribute to the loss of protection from CHD that has been observed in SLE.     

Motorcycle casualties sustained during daytona beach bike week 2000: lessons learned

Study objective: In March 2000, an estimated 500,000 people attended an annual motorcycle rally in Daytona Beach, FL, where approximately 64,000 residents live year-round. The media reported 15 deaths during this 10-day event. To more comprehensively assess the extent of trauma and need for emergency medical care, we investigated all motorcycle crashes, regardless of outcome. Methods: Motorcycle-related crash data from local medical examiner, hospital, emergency medical services (EMS), and police sources were linked. Frequencies of crashes, injuries, hospitalizations, and deaths were determined, and EMS use data were analyzed. Results: During Bike Week 2000, 570 people were involved in 281 motorcycle-related crashes. Two hundred thirty (40%) people were injured, of which 147 (64%) sought treatment in emergency departments, 72 (31%) were hospitalized, and 11 (5%) died. In crashes between motorcycles and passenger cars, individuals exposed as motorcycle occupants were 8.7 times more likely to be injured than car occupants (95% confidence limit 1.7, 15.7). Of 205 EMS dispatches for motorcycle-related crashes, two thirds resulted in transport to an ED. Data needed to assess known risk factors (eg, alcohol use, speed, lack of helmet use) were not routinely ascertained at either the crash site or ED. Conclusion: Although fatalities first called attention to the problem, nonfatal injuries outnumbered deaths 20:1. The manpower resources of civil service and health resources could become overwhelmed or exhausted in circumstances in which many people are injured or killed throughout a relatively long period. The situation deserves future study. Better risk factor surveillance is needed to help prevent crashes. [Ann Emerg Med. 2003;41:792-797.]     

Induction of GDF-15/NAG-1/MIC-1 in human lung carcinoma cells by retinoid-related molecules and assessment of its role in apoptosis

Growth and Differentiation Factor-15 (GDF-15, NAG-1, MIC-1) is induced by several apoptosis-inducing agents including the retinoid-related molecule (RRM) 6-[3-(1-adamantyl-4-hydroxyphenyl]-2-naphthalene carboxylic acid (CD437). It has been suggested that GDF-15 may be involved in the induction of apoptosis by CD437 in H460 lung cancer cells. The present study was designed to probe this hypothesis more directly. Several RRMs (CD437, ST1926 and MX3350-1) but not the retinoids all-trans- retinoic acid and 4HPR were able to induce GDF-15 in H460 cells. A similar differential effect of these retinoids was observed for the induction of p53, which has been reported to regulate GDF-15 expression. In H460 cells transfected with a neo vector control (H460-Neo), treatment with RRMs but not ATRA or 4HPR resulted in increases in p53, GDF-15 and apoptosis evidenced by poly(ADP ribose) polymerase (PARP) cleavage. In contrast, RRMs failed to increase p53 or induce apoptosis in H460 cells in which p53 was inactivated by transfection of the human papillomavirus E6-6 (H460-E6-6). The increase in GDF-15 by RRMs was also compromised in the H460-E6-6 cells. Because PARP cleavage was only evident when GDF-15 levels where elevated it appeared that GDF-15 was mediating the pro-apoptotic effects of RRMs. However, silencing of GDF-15 induction by RNA interference failed to decrease the ability of CD437 and ST1926 to induce apoptosis. These results demonstrate that GDF-15 is dispensable for the pro-apoptotic activity of CD437 and ST1926.     

Comparative study of protamine chloride and sulphate in relation to the heparin rebound phenomenon

The heparin rebound phenomenon is observed when protamine sulphate, but not protamine chloride, is employed for the neutralization of heparin. On investigating the stability of several protamine compounds towards the protaminolytic activity of human plasma, we found that while protamine chloride was stable, both the sulphate and the phosphate were degradeable. The free base showed intermediary stability which persisted upon its conversion to either chloride or sulphate. Likewise, conversion of the sulphate into the chloride by means of an ion exchange column, did not alter its sensitivity. Apparently, the stability of protamine derivatives is not influenced by the specific anion bound to them but is rather acquired in the course of the manufacturing procedures involved in their preparation.     

Activation of coagulation in amniotic fluid during normal human pregnancy

Introduction

Amniotic fluid (AF) is an important medium for fetal development which exhibits high procoagulant activities; however, the role of these procoagulants during pregnancy has not been elucidated and might be associated with pregnancy complications. The current study aimed to evaluate factor X (FX) activation and its association with tissue factor (TF), tissue factor pathway inhibitor (TFPI) and coagulation activation markers in AF during normal human pregnancy.

Methods

Activation of FX and concentration of TF, free TFPI, D-dimer and prothrombin fragments (F1 + 2) were evaluated in AF samples obtained for chromosome analysis from 91 women with normal pregnancy: 65 samples were taken from patients at 16-20 weeks of gestation, 9 samples were drawn at 21-30 weeks and 17 samples−after 30 weeks of gestation.

Results

Activation of FX in AF significantly increased during normal pregnancy (from 65 ± 41 to 205 ± 80 equivalent RVV ng/mg total protein, P < 0.0001). TF and TFPI levels in AF also rose with gestational age. In contrast, the AF concentration of D-dimer and F1 + 2, markers of coagulation activation significantly decreased when expressed per mg total protein. Levels of free TFPI correlated with TF (r = 0.5, P < 0.001), and were 8-fold higher than those of TF during pregnancy.

Conclusion

High levels of TFPI might be associated with the inhibition of procoagulant activity in amniotic fluid during normal pregnancy, which may account for the rarity of clinical amniotic fluid embolism.     

Serum autoantibodies that bind citrullinated fibrinogen are frequently found in patients with rheumatoid arthritis

OBJECTIVE: Autoantibodies that bind citrullinated antigens are a sensitive and specific marker for rheumatoid arthritis (RA). While synthetic cyclic citrullinated peptides (CCP) are typically used to identify these antibodies, little is known about antibody reactivity to the predominant citrullinated protein found in the inflamed synovium, citrullinated fibrinogen (CitFib). We assessed the prevalence of anti-CitFib antibodies in patients with various rheumatic diseases. METHODS: In total, 65 patients with established RA and 63 patients with other rheumatic diseases were tested for serum IgM rheumatoid factor (RF), IgG anti-CCP2, and IgG anti-CitFib antibodies. This cohort was used to determine optimal positive cutoff values for antibody reactivity to CitFib through receiver operating characteristic curve analysis. The specificity of these assays was confirmed with sera from 49 patients with psoriatic arthritis. RESULTS: Antibodies to both citrullinated antigens were identified in the majority of RA patients tested. The overall sensitivity and specificity of the assays were: CCP 82%, 96%, CitFib 75%, 98%, and IgM RF 80%, 64%, respectively. All but one patient that was positive for CitFib was also positive for CCP2, and close to half the RF-negative RA patients were positive for CitFib and CCP2. CONCLUSION: These results suggest that autoimmunity to CitFib is common in patients with RA and may play a role in disease pathogenesis.     

Ethnic variation in disease patterns and health outcomes in systemic lupus erythematosus

OBJECTIVE: In a single-center multiethnic lupus cohort, to investigate the influence of ethnicity on the prevalence of cumulative renal and central nervous system (CNS) lupus disease and damage, overall end-organ damage, and mortality. METHODS: Clinical features, end-organ damage, and mortality were compared by ethnic origin among patients at a lupus clinic followed prospectively in a longitudinal design over a 32-year period. Statistical analysis to compare demographic features, cumulative disease manifestations, and damage included chi-square test as well as linear, logistic, and Poisson regressions adjusting for disease duration, age at diagnosis, and presence of dialysis and hypertension. Kaplan-Meier and proportional hazard analyses were performed to compare survival. RESULTS: There were a total of 1017 patients: 853 Caucasian, 88 African-Canadian, and 76 Chinese-Canadian. Age at diagnosis was younger and disease duration was shorter for Chinese-Canadians compared to Caucasians, but similar between African-Canadians and Caucasians. There was no significant difference in CNS disease, comparing Caucasians to Chinese-Canadians. However, CNS disease was greater in African-Canadians than Chinese-Canadians. There was no significant difference between ethnic groups in CNS damage. Renal disease was more common in African-Canadians than Caucasians, with no significant difference between Caucasian and Chinese-Canadian patients. Renal damage was more common in African-Canadians and Chinese-Canadians than Caucasians. There was no significant difference in mortality among the 3 ethnic groups. CONCLUSION: In this single referral center cohort study, there was no significant difference in CNS damage or mortality among the 3 ethnic groups. African-Canadians had a higher prevalence of renal disease and damage. Further investigation into other determinants such as genetic predisposition, treatment, and cultural perceptions is needed.