Do immature platelet levels in chest pain patients presenting to the emergency department aid in the diagnosis of acute coronary syndrome?

INTRODUCTION: Early and accurate identification of acute coronary syndrome (ACS) vs. noncardiac chest pain in patients presenting to the emergency department (ED) is problematic and new diagnostic markers are needed. Previous studies reported that elevated mean platelet volume (MPV) is associated with ACS and predictive of cardiovascular risk. MPV is closely related to the immature platelet fraction (IPF), and recent studies have suggested that IPF may be a more sensitive marker of ACS than MPV. The objective of the present study was to determine whether the measurement of IPF assists in the diagnosis of ACS in patients presenting to the ED with chest pain. METHODS: In this single-center, prospective, cross-sectional study, adult patients presenting to the ED with chest pain and/or suspected ACS were considered for enrollment. Blood samples from 236 ACS-negative and 44 ACS-positive patients were analyzed in a Sysmex XE-2100 for platelet count, MPV, IPF, and the absolute count of immature platelets (IPC). RESULTS: Total platelet counts, MPV, IPF, and IPC were not statistically different between ACS-negative and ACS-positive patients. The IPF was 4.6 ± 2.7% and 5.0 ± 2.8% (mean ± SD, P = 0.24), and the IPC was 10.0 ± 4.6 and 11.5 ± 7.5 × 10(3) /µL (P = 0.27) for ACS-negative and ACS-positive patients, respectively. CONCLUSION: In 280 patients presenting to the ED with chest pain and/or suspected ACS, no differences in IPF, IPC or MPV were observed in ACS-negative vs. ACS-positive patients, suggesting that these parameters do not assist in the diagnosis of ACS.

Activator protein 1 activation following hypoosmotic stress in HepG2 cells is actin cytoskeleton dependent.

BACKGROUND: Following hypoosmotic stress-induced cell volume change, the actin cytoskeleton reorganizes itself. The role of this reorganization in the activation of the phosphatidylinositol 3-OH-kinase/protein kinase B/activator protein 1 (PI-3-K/PKB/AP-1) proliferative signaling cascade is unknown. Focal adhesion kinase (FAK) participates in the cytoskeleton-based activation of PI-3-K. We hypothesized that hypoosmotic stress-induced activation of PKB and AP-1 in HepG2 cells is dependent on an intact actin cytoskeleton and subsequent FAK phosphorylation. METHODS: HepG2 cells were incubated for 1 h with or without 20 microM cytochalasin D, an actin disrupter, and were then exposed for up to 30 min to hypoosmotic medium (200 mOsm/L) to induce swelling. Tumor necrosis factor alpha (1.4 nM) and medium alone served as positive and negative controls, respectively. Western blots measured cytoplasmic phosphorylated or total FAK and PKB. EMSAs measured nuclear AP-1. All experiments were performed in triplicate. RESULTS: Exposure to hypoosmotic stress resulted in activation of the following signaling messengers in a sequential fashion: (1) phosphorylation of FAK occurred by 2 min, (2) phosphorylation of PKB occurred by 10 min, (3) nuclear translocation of AP-1 occurred by 30 min. All three signaling events were abolished when these cells were pretreated with cytochalasin D. CONCLUSION: Actin reorganization following hypoosmotic stress is essential for the FAK-mediated activation of the PI-3-K/PKB/AP-1 proliferative cascade. These data delineate a possible mechanism by which the cell swelling-induced cytoskeletal changes can initiate proliferative signal transduction in human liver cancer.

Hypoosmotic stress stimulates growth in HepG2 cells via protein kinase B-dependent activation of activator protein-1.

Although hypoosmotic stress-induced cell swelling activates phosphatidylinositol-3-kinase, its impact on the downstream signal protein kinase B and cell growth is unknown. Activator protein-1 is in part phosphatidylinositol-3-kinase dependent, and is important in proliferation. We hypothesized that cell swelling modulates proliferation in HepG2 cells via the protein kinase B-dependent activation of activator protein-1. HepG2 cells pretreated with or without LY294002 were exposed for up to 30 minutes to hypoosmotic medium (160 mOsm/L). Tumor necrosis factor-alpha (1.4 nmol/L) or normoosmolar medium (270 mOsm/L) served as positive and negative controls, respectively. Western immunoblots measured cytoplasmic phosphorylated and total protein kinase B. Electromobility shift assays measured nuclear activator protein-1. Methylene blue assays measured cell proliferation at 24, 48, and 72 hours after stimulation. Hypoosmotic stress phosphorylated protein kinase B by 10 minutes. Subsequently, hypoosmotic exposure stimulated activator protein-1 by 30 minutes. Pulse exposure to hypoosmotic stress potentiated HepG2 proliferation by 72 hours as compared to both negative controls and LY-inhibited cells (n = 4 per group, P = 0.009 and P = 0.004, respectively; P <0.001 analysis of variance. All three activation events were abolished with LY294002 pretreatment. In HepG2 cells, hypoosmotic stress-induced swelling stimulates proliferation via protein kinase B-mediated activation of activator protein-1. These data delineate a possible mechanism linking changes in cell volume to growth in human liver cancer.

Hypoosmotic stress activates p38, ERK 1 and 2, and SAPK/JNK in rat hepatocytes.

BACKGROUND: Following hepatocyte injury, changes in the perihepatocyte milieu modulate cell volume and influence growth. Hypoosmotic stress activates nuclear factor-kappa B (NF-kappaB), a transcription factor believed to prime cell cycle progression in hepatocytes. In this study, we investigate the role of mitogen-activated protein kinases (MAPKs) in the activation of NF-kappaB. MATERIALS AND METHODS: Quiescent primary hepatocytes were exposed to hypoosmotic serum-free William's E (WE) medium (200 mOsm/liter), with or without a 1-h pretreatment with either PD 98059 (15 microM) or SB 202190 (3 microM). Parallel experiments were conducted using hepatocyte growth factor (HGF) at 0.1 mg/ml and normoosmotic WE medium as positive and negative controls, respectively (n = 3). Relative densitometries of Western blots measured phosphorylated cytoplasmic p38, ERK 1 and 2, and SAPK/JNK. Electromobility shift assays examined nuclear NF-kappaB activation. RESULTS: (i) Hypoosmolar WE medium phosphorylated p38, ERK 1 and 2, and SAPK/JNK by 5 min. (ii) Hypoosmolar WE medium activated NF-kappaB at 60 min. (iii) HGF phosphorylated all three MAPKs and activated NF-kappaB with profiles similar to those of hypoosmotic stress. (iv) Both PD 98059 and SB 202190 abrogated the activation of NF-kappaB in HGF-stimulated cells but not in hypoosmotically stressed cells. CONCLUSION: (i) Both hypoosmotic cell swelling and HGF phosphorylate p38, ERK 1 and 2, and SAPK/JNK, and (ii) HGF, but not hypoosmotic stress, activates NF-kappaB via p38 and ERK 1 and 2 phosphorylation. These data suggest that cell swelling activates NF-kappaB through a pathway separate from that of growth factors.

Mesenteric and celiac duplex scanning: a validation study.

PURPOSE: To validate the accuracy of previously established duplex ultrasound criteria for > or =50% superior mesenteric artery (SMA) and celiac artery (CA) stenosis by comparison with arteriography. METHODS: Duplex criteria established retrospectively in our laboratory in 1991 identified an end-diastolic velocity (EDV) > or =45 cm/sec, or no flow signal, as highly sensitive (100%) and specific (92%) indicators for SMA stenosis > or =50% or occlusion. EDV was more accurate (95%) than peak systolic velocity (PSV), which had a maximal accuracy of 86% at a PSV > or =300 cm/sec, with low sensitivity (62%), but high specificity (100%). For CA, accurate velocity thresholds were not identified, but we subsequently noted that retrograde common hepatic artery flow direction from SMA collateral was highly predictive of severe CA stenosis or occlusion. Since publication of those findings, 243 mesenteric duplex scans were performed for clinical evaluation of suspected chronic mesenteric ischemia. Angiographic confirmation was available for a subset of 46. SMA and CA diameters were measured on lateral aortograms by observers blinded to the duplex results, and the original duplex diagnostic criteria were tested for accuracy. In addition, receiver operator characteristic curve analysis was performed on the velocity data to identify the most accurate velocity thresholds in the new data. RESULTS: Duplex was technically adequate in 98% of SMA, 96% of CA, and 89% of hepatic arteries, and arteriograms were adequate in 100% of SMA and 98% of CA. For the SMA, EDV > or =45 cm/sec again provided the best sensitivity (90%), specificity (91%), positive predictive value (90%), negative predictive value (91%), and overall accuracy (91%). As in the retrospective study, PSV > or =300 cm/sec provided low overall accuracy (81%), low sensitivity (60%), but high specificity (100%). Lowering the PSV threshold improved sensitivity but reduced accuracy. For CA, retrograde common hepatic artery flow direction was 100% predictive of severe CA stenosis or occlusion. Velocity data in CA provided accuracy not found in the original study. EDV > or =55 cm/sec or no flow signal had best overall accuracy (95%) with high sensitivity (93%) and specificity (100%). PSV > or =200 cm/sec or no signal also had excellent accuracy (93%), sensitivity (93%), and specificity (94%). In addition, three of four anatomic anomalies were correctly identified by duplex. These included one right hepatic and one common hepatic artery originating from the SMA, and one common celiacomesenteric trunk. CONCLUSION: This validation analysis confirms that duplex velocity criteria are accurate in the identification of mesenteric occlusive disease. Retrograde common hepatic artery flow direction correctly predicts severe CA stenosis or occlusion. Duplex ultrasound may also identify mesenteric anatomic variants that can influence study interpretation.

Deaths in gynecology. A comparative study (1944, 1970).

PIP: An analysis of 401 gynecologic deaths occurring at the Charity Hospital of Louisianna in New Orleans from April 1961 to January 1969 was compiled for comparison with a similar study (401 fatalities) conducted at the same medical facility in 194 (Miller). In the Miller series, the age factor displayed a gradual rise to 45 years followed by a gradual decline. In the 366 malignant cases collected in 1970, ages ranged from 13 (ovarian cancer) to 100 years plus, and 177 patients were under age 50. 40% of the earlier cases were benign and explain the earlier peak while the higher age peak for 1970 may be the result of the fact that women live longer and well into the age period in which malignancy is more likely to develop. Generally the women in the 1970 series, both clinically and statistically, were in fairly good condition; the poor or moribund status of some was chiefly caused by their malignant disease. Unlike the 1944 series, preoperative preparations were generally good, though in over half the cases, the patients were poor risks for any therapy. The earlier series displayed many complications, some of which were extremely serious and some of which were poorly handled, while peritonitis, pulmonary complications and embolus all showed significant decreases in the 1970 series. Cardiovascular and renal diseases, especially uremia (46 cases) were the most frequent causes of death after cancer. In the 1944 series, eight patients displayed or had a history of multiple malignant diseases; the 1970 series had 26 such cases. Carcinoma of the cervix was a major problem in both studies, accounting for 167 of the 247 deaths from malignant disease in the earlier study and for 209 out of 366 in the later investigation which also included 50 deaths from carcinoma of the endometrium. The age range in the 1970 series was from 23 to over 100 years, and less than half the patients sought medical advice within a year of developing symptoms. In the 1944 series, the delay was even longer. Only half the patients in the later series were first seen at a time when the stage of the disease was still favorable to cure. In both series, bleeding was the most frequent first symptom, but appears to have been disregarded as an inconvenience due to its painlessness by the patient or regarded as part of the menopausal pattern by physicians and thereby untested. The age range among 50 cases of endometrial cancer was from 31 to 82 years and the time lag between symptoms and admission was 0 to 13 years. The second largest number of fatalities in both series was from ovarian cancer. Among 59 1970 cases, the age range was from 13 to 72 years and the time lag reached six years in one case. Better surgical techniques, combined with irradiation and chemotherapy have improved treatment of this pelvic cancer since 1944, but generally significant improvement in the treatment of malignancies has yet to be achieved. In the 1970 series, outside physicians could be blamed for 17 of 366 deaths from malignant disease and the hospital staff for 47. Physicians should communicate the following facts: 1) any discharge and any kind of abnormal bleeding may indicate cancer and demands prompt testing; 2) all women over 30 years of age should have a pelvic twice yearly; 3) all women in this age group should also receive a biannual Pap test, which ideally should be given any time a woman has contact with a physician.^ieng