Effect of a Contrast Modulation System on Contrast Media Use and the Rate of Acute Kidney Injury After Coronary Angiography

Objectives

The aim of the AVERT (AVERT Clinical Trial for Contrast Media Volume Reduction and Incidence of CIN) trial was to test the efficacy of the AVERT system to reduce the contrast media volume (CMV) used during coronary angiographic procedures without impairing image quality and to prevent contrast-induced acute kidney injury (CI-AKI) in patients at risk for CI-AKI.

Higher body weight patients on clopidogrel maintenance therapy have lower active metabolite concentrations,lower levels of platelet inhibition,and higher rates of poor responders than low body weight patients

Body weight is a predictor of clopidogrel response. However, no prospective studies have compared pharmacodynamic (PD) and pharmacokinetic (PK) data based on body weight. We compared PD and PK effects of clopidogrel 75 mg in low body weight (LBW, <60 kg) and higher body weight (HBW, ≥60 kg) patients with stable coronary artery disease. LBW (n = 34, 56.4 ± 3.7 kg) and HBW (n = 38, 84.7 ± 14.9 kg) aspirin-treated patients received clopidogrel 75 mg for 10–14 days. The area under the concentration–time curve of active metabolite (Clop-AM) calculated through the last quantifiable concentration up to 4 h postdose, AUC_(0–tlast), was calculated by noncompartmental methods. Light transmission aggregometry (LTA) (maximum platelet aggregation and inhibition of platelet aggregation to 20 μM adenosine diphosphate (ADP), and residual platelet aggregation to 5 μM ADP), VerifyNow^® P2Y12 reaction units (PRU), and vasodilator-associated stimulated phosphoprotein phosphorylation platelet reactivity index (VASP–PRI) were performed. Mean AUC_(0–tlast) was lower in HBW than LBW patients: 12.8 versus 17.9 ng h/mL. HBW patients had higher platelet reactivity as measured by LTA (all p ≤ 0.01), PRU (207 ± 68 vs. 152 ± 57, p < 0.001), and VASP–PRI (56 ± 18 vs. 39 ± 17, p < 0.001). More HBW patients exhibited high on-treatment platelet reactivity (HPR) using PRU (35 vs. 9 %) and VASP–PRI (65 vs. 27 %). Body weight correlated with PRU and VASP–PRI (both p < 0.001), and inversely with log transformed AUC_(0–tlast) (p < 0.001). In conclusion, HBW patients had lower levels of Clop-AM, and higher platelet reactivity and rates of HPR than LBW subjects, contributing to their suboptimal response to clopidogrel.     

Exisulind in combination with celecoxib modulates epidermal growth factor receptor, cyclooxygenase-2, and cyclin D1 against prostate carcinogenesis: in vivo evidence.

PURPOSE: Nonsteroidal anti-inflammatory drugs mediate anticancer effects by modulating cyclooxygenase-2 (COX-2)-dependent and/or COX-2-independent mechanism(s); however, the toxicity issue is a concern with single agents at higher doses. In this study, we determined the combined effect of celecoxib, a COX-2 inhibitor, along with exisulind (sulindac sulfone/Aptosyn) at low doses in prostate cancer. EXPERIMENTAL DESIGN: We used a sequential regimen of N-methyl-N-nitrosourea + testosterone to induce prostate cancer in Wistar-Unilever rats. Following carcinogen treatment, celecoxib and exisulind individually and their combination at low doses were given in NIH-07 diet for 52 weeks. We determined the incidence of prostatic intraepithelial neoplasia, adenocarcinomas, rate of tumor cell proliferation, and apoptosis. Immunohistochemical and Western blot analysis were done to determine COX-2, epidermal growth factor receptor (EGFR), Akt, androgen receptor, and cyclin D1 expression. Serum prostaglandin E2 and tumor necrosis factor-alpha levels were determined using enzyme immunoassay/ELISA assays. RESULTS: The rats that received celecoxib in combination with exisulind at low doses showed a significant decrease in prostatic intraepithelial neoplasia and adenocarcinomas as well as an enhanced rate of apoptosis. An overall decrease in COX-2, EGFR, Akt, androgen receptor, and cyclin D1 expression was found associated with tumor growth inhibition. Reduced serum levels of COX-2 protein, prostaglandin E2, and tumor necrosis factor-alpha indicated anti-inflammatory effects. A strong inhibition of total and phosphorylated form of EGFR (Tyr(992) and Tyr(845)) and Akt (Ser(473)) was significant in rats given with these agents in combination. CONCLUSIONS: In this study, we show for the first time that the combination of celecoxib with exisulind at low doses could prevent prostate carcinogenesis by altering key molecular events.     

Bilateral choroid plexus cysts in trisomy 21.

Whether karyotyping is indicated in a fetus with choroid plexus cysts who is otherwise structurally normal is still controversial. Many authors have suggested basing the decision on cyst size, bilaterality, persistence with advancing gestational age, and association with other anomalies. We report a case of large bilateral choroid plexus cysts in a fetus with trisomy 21 who had no evidence of congenital anomalies or ultrasonographic signs of Down syndrome. Cyst sizes diminished by half over a 3-week period of follow-up. It appears that diminishing size alone should not be considered sufficient reassurance about the normality of the fetal karyotype. A similar case has been previously reported, and it is conceivable that choroid plexus cysts are associated not only with trisomy 18 but also with trisomy 21.     

Growth retardation and dystrophy in Crohn's disease

A 14 year old boy with Crohn's disease of the small bowel had a seven year history of growth failure and severe dystrophy. This case demonstrates the significance of growth failure, catch-up growth and intestinal obstruction for children with Crohn's disease.     

Complications of the dilatation of Stensen's duct: stenosis and lithiasis

A recent publication noted the apparent lack of serious complications of dilatation of salivary canals, based on a review of 16 cases. This is contested by the report of three cases of dilatation of Stensen's duct complicated by lithiasis and stenosis, with associated canalar pseudo-cysts. Surgical excision was required and allowed study of histopathology of this affection.     

An Alternative Technique for Creating the Gastrojejunostomy in Laparoscopic Roux-en-Y Gastric Bypass: Experience with 28 consecutive patients

Background:This study illustrates our experience in laparoscopic Roux-en-Y gastric bypass (LRYGBP) using a new technique for creating the gastrojejunostomy. Methods: Between April and November 1999, 28 patients underwent LRYGBP. In the first 10 patients the transoral route with endoscopic guidance was utilized for placement of the anvil in the gastric pouch. A new totally intra-peritoneal approach was utilized in the next 18 patients, avoiding the transoral route. Results:There were 23 women and 5 men with an average age of 36 years (range 24-51). The mean BMI was 47, with range 41-64. Of the patients, 82% had one or more associated co-morbid conditions (hypertension, diabetes, sleep apnea, arthritis). Average operative time in the first 10 patients using the trans-oral route with endoscopic guidance was 340 minutes (range 240-390 min). The next 18 patients underwent totally intra-peritoneal anvil placement with a 240-minute average operating time (range 150-310 min). There were no open conversions or mortalities.There were 4 complications, including 2 wound infections, one urinary tract infection, and one intra-abdominal abscess. The two wound infections occurred in the first 10 patients that underwent trans-oral introduction of the anvil. Conclusions: LRYGBP was a safe and feasible operation. We believe that our technique is easily reproducible, avoiding the trans-oral route for introducing the anvil. This technique may also decrease operative time and possibly the incidence of wound infections, although we are still in the learning curve and final conclusions cannot be made.     

Programming of Cells for Death under Defined Experimental Conditions: Relevance to the Tumor Problem

An attempt was made in this study to determine more precisely the nature of the factors that are involved in the programming of cells for a form of terminal cellular differentiation that results in death. These studies demonstrated that both the cytokinesins, which are potent inhibitors of plant and animal adenosine 3':5'-cyclic monophosphate phosphodiesterases, and 8-bromoadenosine 3':5'-cyclic monophosphate, which is a stable, biologically active form of adenosine 3':5'-cyclic monophosphate, are highly effective in encouraging differentiation of parenchyma cells into tracheary elements with accompanying death. Since adenosine 3':5'-cyclic monophosphate and theophylline when used together were also effective, the results reported here suggest that adenosine 3':5'-cyclic monophosphate is somehow importantly involved in the conversion of parenchyma cells into tracheary elements in this system. The possible significance to the tumor problem generally of the programming of cells for terminal differentiation, with or without resulting death, is discussed.     

Maintenance Dosage as a Critical Factor in Methadone Maintenance Treatment*

This study concentrates on methadone dosage as a critical factor influencing abuse of other psychoactive drugs (including alcohol) by patients maintained on methadone. The study population were patients who remained on methadone for at least two years. The effects of dosage level on a group of 46 patients (low dosage n=27, ×= 48.32; high dosage n = 19, ×= 86.43) is reported. Significant increases (p < 0.01) were found in the abuse of barbiturates, ataractics, and alcohol for the low dosage group. Dosage level had no significant relationship with heroin and amphetamine abuse. These results suggest that higher doses of methadone may provide the patients with a generalized central nervous system depressive effect.