Diagnosing breast implant rupture with MR imaging, US, and mammography

A total of 135 symptomatic women with 262 breast implants were examined with magnetic resonance (MR) imaging performed with a body coil, ultrasound (US), or both to determine imaging features of implant rupture. Surgical proof was available for 33 women with 62 implants; 24 were ruptured and 38 were intact. Complicated internal structure was the most reliable predictor of implant rupture: Diffuse low-level echoes were seen on sonograms in 56% of ruptured implants; internal membranes (which correspond to the collapsed implant shell) were seen on MR images in 58% of ruptured implants. Fluid droplets were seen within the silicone in 26% of ruptured implants on MR images. Irregular implant contour can be a sign of rupture but is unreliable. Fluid collections around silicone implants are not a sign of rupture. At present, neither US nor conventional MR imaging with a body coil is sufficiently reliable to advocate routine screening of asymptomatic women with breast implants. Evaluation with MR imaging performed with a surface coil is more reliable.     

Non-ACTH POMC fragments stimulate aldosterone production by human adrenal cells in vitro

The possibility that non-ACTH proopiomelanocortin-derived fragments may stimulate aldosterone production has previously been studied using nonhuman cells with inconsistent results. We have examined the response of aldosterone to beta-endorphin (beta-End) and joining peptide (JP) and compared these with the response to ACTH using eight cell suspensions prepared from human adrenal glands. ACTH, 10(-6), 10(-8), and 10(-10) M, consistently stimulated aldosterone accumulation above that occurring in unstimulated cells (150 +/- 83, 120 +/- 62, and 77 +/- 32 fmol/10(4) cells above basal, respectively; mean +/- SE; p < 0.05). beta-End significantly stimulated aldosterone production at 10(-6) and 10(-8) M (114 +/- 84 and 50 +/- 24 fmol/10(4) cells above basal; p < 0.05); 10(-10) M beta-End did not provide significant stimulation. Furthermore, JP stimulated aldosterone biosynthesis (41 +/- 16 fmol/10(4) cells above basal; p < 0.05), only at the highest concentration used, 10(-6) M. The addition of 10(-8) M ACTH plus 10(-6) and 10(-10) M beta-End to human adrenal cells yielded values significantly greater than those achieved with either agent alone (267 +/- 152 and 183 +/- 89 fmol/10(4) cells above basal; p < 0.05). These data indicate for the first time that beta-End and JP have the capacity to stimulate aldosterone production in human adrenal cells in vitro. The physiological and potential clinical significance of these observations has yet to be elucidated.     

Inactivation of cytochrome P450 2E1 by tert-butylisothiocyanate

Several naturally occurring and synthethic isothiocyanates were evaluated for their ability to inactivate the major ethanol-inducible hepatic cytochrome P450 2E1. Of the compounds tested, tert-butylisothiocyanate (tBITC) was found to be the most selective inactivator of the 2E1 p-nitrophenol hydroxylation activity. tBITC was more specific for inactivating P450 2E1 activity than for rat P450 1A1, 1A2, 3A2, and 2B1, or the human cytochromes P450 3A4 and 2B6. The kinetics of inactivation of P450 2E1 by tBITC were characterized. P450 2E1, either in rat liver microsomes or in a purified reconstituted system containing the bacterially expressed rabbit cytochrome, was inactivated by tBITC in a mechanism-based manner. The loss of activity followed pseudo-first-order kinetics and was NADPH- and tBITC-dependent. The maximal rates for inactivation of P450 2E1 in microsomes or for the purified P450 2E1 at 30 degrees C were 0.72 and 0.27 min-1 and the apparent KI values were 11 and 7.6 microM, respectively. When cytochrome b5 was co-reconstituted with P450 2E1, the apparent KI for P450 2E1 inactivation by tBITC was similar to that seen in microsomes (14 microM). P450 2E1 T303A was also inactivated by tBITC with kinetic constants similar to that of the wild type enzyme. Co-incubations with an alternate substrate protected P450 2E1 from inactivation by tBITC. The extent of P450 2E1 inactivation by tBITC resulted in a comparable loss of the ability of the enzyme to form a reduced CO complex.     

Acute von Willebrand factor secretion from the endothelium in vivo: assessment through plasma propeptide (vWf:AgII) Levels

STUDY OBJECTIVES: Patients with coronary heart disease (CHD) and obstructive sleep apnea may have an increased cardiac risk due to nocturnal myocardial ischemia triggered by apnea-associated oxygen desaturation. Sleep structure in patients with obstructive sleep apnea is fragmented by activation of the central nervous system (CNS) (arousal) due to obstructive apneas. Nocturnal myocardial ischemia may lead to activation of the CNS as well. PATIENTS: Fourteen patients with obstructive sleep apnea and CHD disease and seven patients suffering from obstructive sleep apnea without CHD were studied. Overnight sleep studies and simultaneous six-lead ECG recordings were performed. In addition, sleep studies and ECG recordings were performed with administration of a sustained-release nitrate in these patients in a double-blinded crossover design. RESULTS: Analysis of three nights' recordings revealed 144 episodes of nocturnal myocardial ischemia in six subjects. Five patients had underlying CHD and one patient exhibited diffuse wall defects of the coronary arteries; also, 85.4% of ischemic episodes were concomitant with apneas and oxygen desaturation > 3%, and 77.8% of ischemic episodes occurred during rapid eye movement (REM) sleep, although total amount of REM sleep was only 18% of total sleep time. Mean oxygen saturation was significantly lower (p < 0.05) during apnea-associated ischemic episodes than during nonapnea-associated ischemia (77.3% vs 93.1%). Nitrate administration did not reduce ischemic episodes. Sleep architecture (macrostructure) exhibited a reduction in sleep stages non-REM 3 and 4 and REM sleep. Comparing the microstructure of sleep (arousals) within episodes with and without ischemia but similar criteria like sleep stage, apnea activity, and oxygen saturation, we found significantly more (p < 0.01) and severe (p < 0.001) arousals during periods with myocardial ischemia than during control episodes. In addition, microstructure of sleep was disturbed by myocardial ischemia itself in absence of apneas. CONCLUSION: It is concluded that patients with CHD and obstructive sleep apnea are endangered by apnea-associated ischemia and that these ischemic episodes lead to activation of the CNS and additional fragmentation of sleep. Patients with nocturnal ischemia should be screened for underlying sleep apnea even if nitrate therapy fails.     

Long-term treatment of ulcerative colitis with ciprofloxacin: a prospective, double-blind, placebo-controlled study

BACKGROUND & AIMS: Although bacterial bowel flora may be one of the contributing factors in the pathogenesis of chronic mucosal inflammation, antibiotic treatment has no established role in ulcerative colitis. The aim of the study was to evaluate the role of ciprofloxacin in the induction and maintenance of remission in ulcerative colitis in patients responding poorly to conventional therapy with steroids and mesalamine. METHODS: Ciprofloxacin (n = 38; 500-750 mg twice a day) or placebo (n = 45) was administered for 6 months in a double-blind, randomized study with a high but decreasing dose of prednisone and maintenance treatment with mesalamine including follow-up for the next 6 months. Clinical assessment and colonoscopic evaluation were performed at 0, 3, 6, and 12 months. Treatment failure, the primary end point, was defined as both symptomatic and endoscopic failure to respond. RESULTS: During the first 6 months, the treatment-failure rate was 21% in the ciprofloxacin-treated group and 44% in the placebo group (P = 0.02). Endoscopic and histological findings were used as secondary end points and showed better results in the ciprofloxacin group at 3 months but not at 6 months. CONCLUSIONS: Addition of a 6-month ciprofloxacin treatment for ulcerative colitis improved the results of conventional therapy with mesalamine and prednisone.