Increased incidence of cervical intraepithelial neoplasia in women with systemic lupus erythematosus treated with intravenous cyclophosphamide

OBJECTIVE: To determine if the incidence of cervical intraepithelial neoplasia (CIN) is increased in immunosuppressed women with systemic lupus erythematosus (SLE). METHODS: Women with SLE were consecutively recruited from University of Michigan outpatient rheumatology clinics. Women with abnormal cervical smears at screening were excluded. Cervical smears were obtained at baseline and at 3 and 7 years. Cervical biopsies confirmed cytologic abnormalities (CIN I-III), and were scored by pathologists in blinded fashion. Data were analyzed according to treatment group: (1) prednisone; (2) azathioprine (AZA); (3) intravenous cyclophosphamide (IVCYC); and (4) IVCYC + AZA + prednisone. RESULTS: Sixty-one of 89 women screened were eligible for enrollment. The overall 3-year incidence of CIN was 9.8%. Stratified by treatment group, the 3-year incidence of CIN was 0/23 (0%) in prednisone treated patients, 0/4 (0%) in AZA treated patients, 2/8 (25%) in IVCYC treated patients, and 4/26 (15%) in CYC + AZA + prednisone treated patients. A dose relationship was observed between cumulative IVCYC exposure and CIN; each increase of 1 g of IVCYC exposure corresponded to a 13% increased risk of CIN (p = 0.04). At 7 years, 45 patients remained under followup and 6 patients had died of unrelated causes. No cases of CIN were observed at 7 years, although there were 2 cases of atypical squamous cells of unknown significance and one case of condyloma. CONCLUSION: IVCYC + prednisone therapy for SLE is significantly associated with development of CIN.     

An Analysis of Mechanisms Underlying the Antifibrinolytic Properties of Radiographic Contrast Agents

Background: Radiographic contrast agents inhibit fibrinolysis, although by poorly defined pathways. The purpose of this study was to define specific mechanisms by which contrast agents inhibit clot lysis. Methods and Results: Diatrizoate (high osmolar ionic agent), ioxaglate (low osmolar ionic), and ioversol (nonionic) were studied in vitro. Diatrizoate inhibited clot lysis by 81.3±0.6% vs. control (p<0.001). Ioxaglate inhibited clot lysis by 41.7±11.9%, which was of borderline significance (p=0.07). Ioversol did not significantly inhibit clot lysis (14.9±11.5% decrease vs. control; p>0.3). Inhibition of fibrinolysis was not explained by the high osmolarities of contrast agents, by their iodine content, or by their effects on the amidolytic activities of t-PA, urokinase, or plasmin. However, plasminogen activation by t-PA, urokinase, or streptokinase was significantly inhibited by contrast agents. Diatrizoate, ioxaglate, and ioversol inhibited plasminogen binding to plasma clots by 51±4% (p<0.001), 30.1±4% (p<0.01), and 19.4±7% (p=0.07), respectively. Plasma clots formed in the presence of contrast agents were resistant to lysis by plasmin. Diatrizoate produced the most potent effect, inhibiting clot lysis by 40±5.7% (p<0.03). Contrast agents did not inhibit plasminogen binding to fibrin or plasmin-mediated fibrinolysis if they were added after clot formation. Contrast agents altered clot turbidity, an index of fibrin structure, if present during clot formation, but not if added to preformed clots. Contrast agents did not affect plasminogen activator inhibitor-1 or ₂-antiplasmin function. Conclusions: Contrast agents inhibit clot lysis by inhibiting plasminogen activation and by disrupting interactions of plasminogen and plasmin with fibrin by altering fibrin structure. Significant variation in antifibrinolytic properties exists between different contrast agents. Abbreviated Abstract. The purpose of this study was to define specific mechanisms by which contrast agents inhibit clot lysis. In both a purified clot lysis system and a plasma clot lysis system, diatrizoate, an ionic agent, produced the most potent inhibition of fibrinolysis. Contrast agents did not inhibit the active sites of plasminogen activators or plasmin, but did inhibit plasminogen activation. Binding of plasminogen to fibrin and lysis of fibrin by plasmin were inhibited by contrast agents if they were present during clot formation, but not if they were added after clot formation was complete. Contrast agents altered clot turbidity, an index of fibrin structure, if present during clot formation, but not if added to preformed clots. Contrast agents did not affect plasminogen activator inhibitor-1 or ₂-antiplasmin function. The effects of contrast agents on fibrinolytic parameters were not explained by their high osmolarities. These results suggest that contrast agents inhibit clot lysis by inhibiting plasminogen activation and by disrupting interactions of plasminogen and plasmin with fibrin by altering fibrin structure.     

Acute myocardial infarction in two adolescent males

Acute myocardial infarction in previously healthy children is rare in the absence of congenital anomalies. We describe two cases of acute anterior myocardial infarction in adolescent males with no congenital heart disease, without prior history of or risk factors for coronary heart disease, and with no history of drug abuse. These cases illustrate that myocardial infarction in the absence of systemic illness or coronary anomalies can occur in an adolescent population.     

Occult obstructive sleep apnea and clinical outcomes of radiofrequency catheter ablation in patients with atrial fibrillation

Journal of Interventional Cardiac Electrophysiology - Recurrent atrial fibrillation (AF) after successful cardioversion can be predicted by obstructive sleep apnea (OSA) diagnosed by...     

Reported obstructive sleep apnea does not diminish the cardiometabolic health benefits from a comprehensive lifestyle intervention program

Obstructive sleep apnea (OSA) commonly coexists with the metabolic syndrome, a condition for which behavioral changes are often prescribed. Whether OSA diminishes the cardiometabolic health benefits from lifestyle interventions remains unclear. We evaluated 278 consecutive metabolic syndrome participants enrolled in a 12‐week comprehensive lifestyle intervention program. The changes in blood pressure (BP), along with other metabolic health parameters, from baseline to follow‐up were compared between those with and without OSA. Mean age was 52.4 ± 10.9 years and 37% were male. At enrollment, mean body mass index (BMI) was 38.2 ± 7.7 kg/m². OSA was reported in 126 of 269 final participants (47%). At baseline, participants with reported OSA were more likely to be male, older, have a higher BMI, waist and neck size (all P < 0.05). At program completion, participants with (−5.8 ± 16.1/−3.0 ± 10.0 mm Hg) and without OSA (−4.7 ± 13.1/−3.3 ± 8.2 mm Hg) had significant reductions in systolic and diastolic BP as well as BMI, fasting glucose, and triglyceride levels. There were no significant differences in the absolute or percentage changes in BP or other metabolic parameters between groups. Our findings support that patients with the metabolic syndrome can derive substantial health benefits, including reductions in BP, by a lifestyle intervention program regardless of the presence of OSA.