Preterm Labor: CD55 in Maternal Blood Leukocytes

Problem Intrauterine inflammation is a frequent and significant factor associated with the pathogenesis of preterm labor/birth (PTL/PTB). However, it remains unclear whether the intrauterine inflammatory responses activate the maternal peripheral circulation. We explored the association between PTL/PTB and the ‘activation’ of the peripheral circulatory system by determining whether CD55 mRNA expression within peripheral WBCs differed between PTL and control patients not in labor. Method of Study RNA was purified from white blood cells collected from pregnant women with preterm labor (n = 45), and from pregnant (n = 30) control women. CD55 gene expression was evaluated by quantitative PCR. Results The mean CD55 mRNA level within the PTL group (0.77 ± 0.03) was 1.48‐fold higher than that observed (0.52 ± 0.02) within the control group (P < 0.0001); 71% of PTL patients and only 6.7% of control subjects expressed elevated CD55 mRNA. The receiver operating characteristics (with 95% CI) of CD55 as a marker for PTL were as follows: Sensitivity, 69% (53–82%); Specificity, 93% (78–99%); Positive Predictive Value, 94% (80–99%); and Negative Predictive Value, 67% (51–80%). In the patient population that delivered prematurely (before 37 weeks), 81% expressed elevated CD55 mRNA levels with a mean of 0.78 ± 0.03 and 95% CI of 0.71–0.84. The receiver operating characteristics were as follows: Sensitivity, 73% (54–88%); Specificity, 86% (71–95%); Positive Predictive Value, 81.5% (62–94%); and Negative Predictive Value, 80% (64–91%). Conclusion Here we report for the first time that CD55 mRNA expression was elevated in the peripheral WBCs of subjects with preterm labor compared with control gestationally‐matched pregnant woman and that elevated leukocyte CD55 may be a useful predictor of subsequent PTB.     

Efficacy and safety of beating heart coronary revascularization coupled with ascending aorta-bifemoral grafting: Analysis of short term results

Introduction  

Coronary Artery Disease (CAD) frequently coexists with Peripheral Vascular Disease (PVD) and poses management issues. When there is a concomitant infrarenal aortic occlusive disease, abdominal aorta is the traditional donor of bypass inflow to the lower limbs. However, the ascending aorta may also be used as the source of inflow to both the femoral and coronary arteries in patients who present with combined CAD and PVD. Here, 5 year follow up results of simultaneous off-pump coronary artery bypass grafting (OPCAB) and Ascending Aorto-Bifemoral Grafting [AABG] are presented and merits of the procedure are discussed.     

Congenital Aneurysm of Left Atrial Appendage: A Case Report

Abstract   Aneurysm of the left atrial appendage (LAA) is a very infrequent condition. We report a case of a two-year-old child with congenital aneurysm of the LAA with a large thrombus in it. He presented with an episode of seizures with left-sided hemiparesis. Diagnosis was based on transthoracic echocardiography and magnetic resonance imaging. The patient was successfully treated by surgical resection of the aneurysm and removal of the thrombus. (J Card Surg 2010;25:37-40)     

A phase I and pharmacokinetic study of lapatinib in combination with infusional 5-fluorouracil, leucovorin and irinotecan.

BACKGROUND: This study determined the optimally tolerated regimen (OTR) of oral lapatinib administered in combination with infusional 5-fluorouracil (5-FU), leucovorin and irinotecan (FOLFIRI) and assessed the safety, tolerability and pharmacokinetics of the combination. PATIENTS AND METHODS: Twenty-five patients were enrolled; 12 patients were treated at three dose levels to determine OTR; then 13 patients were treated at OTR to evaluate the pharmacokinetics of the combination. RESULTS: The 2-weekly OTR comprised lapatinib 1250 mg/day with irinotecan 108 mg/m(2) (day 1) and leucovorin 200 mg/m(2), 5-FU bolus 240 mg/m(2) and 5-FU infusion 360 mg/m(2) (days 1 and 2); doses of 5-FU and irinotecan represent a 40% reduction in dose compared to conventional FOLFIRI. Dose-limiting toxicities were grade 3 diarrhoea and grade 4 neutropenia. Co-administration of lapatinib increased the area under the plasma concentration-time curve of SN-38, the active metabolite of irinotecan, by an average of 41%; no other pharmacokinetic interactions were observed. Of 19 patients evaluable for disease response assessment, four patients had partial response and nine patients had stable disease. CONCLUSION: The combination of lapatinib and FOLFIRI is safe and demonstrates clinical activity; the documented PK interaction can effectively be compensated by lowering the doses of 5-FU and irinotecan. This regime may be further tested in a phase II trial.     

Prediction of pelvic lymph node metastasis by the ratio of cathepsin B to stefin A in patients with prostate carcinoma

BACKGROUND: Pathologic grade and/or histologic score, extraprostatic extension indicated by invasion of the prostatic capsule, margin, and/or seminal vesicles by prostate cancer cells, serum total prostate-specific antigen (PSA), free PSA, complexed PSA levels and/or their ratios, regional pelvic lymph node metastases, and clinical staging have been used to diagnose and monitor the treatment of prostate carcinoma (PC) patients. The Gleason grading system is also used to grade/score a patient's stage of disease, with lower to higher scores indicating progression of PC. However, Gleason's system cannot be used to distinguish biologically aggressive PCs within a single Gleason score. Our objective was to identify subpopulations (or clones) of aggressive prostate cancers within an individual Gleason score by utilizing biological molecule(s) that also facilitate cancer cell invasion to prostatic stroma and metastasis to the lymph nodes. MATERIALS AND METHODS: Specimens were collected from 97 patients with PC and from 8 patients with benign prostatic hyperplasia. These patients had not been treated with hormonal and/or chemotherapeutic agents before undergoing a prostatectomy at the Minneapolis Veterans Affairs Medical Center. Formalin-fixed, paraffin or paraplast-embedded prostate tissue sections were stained with hematoxylin and eosin for pathologic diagnosis and adjacent sections were stained for for immunohistochemical study. We also collected data on age, race, extraprostatic extension, margin status, seminal vesicle, and lymph node invasion by cancer cells, clinical stage at prostatectomy, and mortality/survival data, including the available presurgery and postsurgery serum total PSA and prostatic acid phosphatase concentrations in patients. Immunohistochemical localization of mouse or rabbit anti-cathepsin B (CB) antibody IgG and mouse antihuman stefin (cystatin) A IgG was quantified using a computer-based image analysis system equipped with Metamorph software. RESULTS: CB and stefin A identified aggressive and less aggressive clones of PCs within an individual Gleason score. Tumors with a Gleason Score of 6 that are similar histologically and morphologically were heterogeneous with respect to the ratios of CB to stefin A (CB > stefin A, CB = stefin A, and CB < stefin A). We also found a significant positive association (P = 0.0066) between ratios of CB and stefin A (CB > stefin A) and the incidence of pelvic lymph node metastases, but not with ratios of CB less than stefin A and/or ratios of CB equal to stefin A. Patients with Gleason 7 PCs had a higher incidence of positive lymph nodes than those with Gleason Score 6 tumors. Our data indicated that mortality rates increased in patients when the ratios of CB were greater than stefin A. CONCLUSIONS: PC within an individual Gleason score is a heterogeneous tumor that contains clones or subpopulations of aggressive and less aggressive tumors that can be defined by the ratios of CB to stefin A. PC with an aggressive clone can be identified when the ratio of CB is greater than that of stefin A. Less aggressive clones are identified when the ratio of CB is less than that of stefin A or when the ratio of CB is equal to that of stefin A. The ratios of CB to stefin A can be used in the differential diagnosis and treatment of patients with PC. This is the first report to identify phenotypes of aggressive and less aggressive PCs within a Gleason score.     

Posterior urethral valves: preliminary observations on the significance of plasma Renin activity as a prognostic marker

PURPOSE: A significant number of children with posterior urethral valves (PUVs) have chronic renal failure due to tubulointerstitial damage. Activation of the renin-angiotensin system is known to inflict this injury. We investigated the role of plasma renin activity (PRA) in patients with PUVs and sought to establish a relationship between renal damage and PRA. MATERIALS AND METHODS: The records of patients with PUVs were reviewed regarding the time of valve ablation, serum creatinine, scars, grade of reflux and glomerular filtration rate (GFR). PRA was measured before and after valve ablation. RESULTS: A total of 25 patients had PUVs (mean age 3.2 +/- 2.4 years, mean period of observation 4.5 +/- 1.2 years). Mean PRA was increased before valve ablation in all patients irrespective of age, and decreased after ablation. Of 25 patients 14 (56%) had renal damage, with a mean PRA of 36 +/- 4.5 ng/ml per hour compared to 26 +/- 8.2 ng/ml per hour in patients with normal renal function (chi-square 4.2 p = 0.01). Of the 14 patients with renal damage 9 (64%) had normal GFR at age 1 year but increased PRA. Of these 14 patients the accepted criteria for renal damage of increased serum creatinine, high grade reflux, scars and decreasing GFR were present in only 6 (43%), 3 (21%), 2 (14%) and 4 (29%), respectively. PRA was increased in all 14 cases. CONCLUSIONS: PRA was increased before valve ablation and decreased after ablation. It is increased in patients with early renal damage. Our preliminary observations indicate that PRA may be helpful in identifying patients with early renal damage.     

Milrinone and Low Cardiac Output Following Cardiac Surgery in Infants: Is There a Direct Myocardial Effect?

We assessed the effect of milrinone on myocardial function in pediatric patients with postoperative low cardiac output syndrome by index of myocardial performance in a prospective, open-label, nonrandomized, consecutive study. Fifteen patients with low cardiac output syndrome following cardiac surgical treatment were studied in the tertiary cardiothoracic pediatric intensive care unit between April 2001 and November 2003 (age range, 0.2–16 months; median, 7; weight, 2.7–11.8 kg; median, 5). Echocardiographic, Doppler-derived, time interval-based index of myocardial performance (Tei index) was used to study cardiac function prior to and while on intravenous milrinone treatment for 18–24 hours. Treatment with milrinone led to improvement in biventricular myocardial function [mean right ventricular index from 0.521 (SD-0.213) to 0.385 (SD-0.215), p = 0.003; mean left ventricular index from 0.636 (SD-0.209) to 0.5 (SD-0.171), p = 0.012). No difference was found in the values of heart rate corrected right or left ventricular ejection time prior to and while on treatment with milrinone (right ventricle: mean, 1.23 (SD-0.42) and 1.14 (SD-0.48), p = 0.29; left ventricles: mean, 1.17 (SD-0.51) and 1.13 (SD-0.48), p = 0.66) Our data support the direct myocardial effect of milrinone as part of the mechanism behind its already proven benefit in children with low cardiac output syndrome following cardiac surgery.