Sudesh Srivastav

Antiestrogenic glyceollins suppress human breast and ovarian carcinoma tumorigenesis

Purpose: We have identified the phytoalexin compounds glyceollins I, II, and III, which exhibit marked antiestrogenic effects on estrogen receptor function and estrogen-dependent tumor growth in vivo. The purpose of this study was to investigate the interactions among the induced soy phytoalexins glyceollins I, II, and III on the growth of estrogen-dependent MCF-7 breast cancer and BG-1 ovarian cancer cells implanted in ovariectomized athymic mice. Experimental Design: Four treatment groups for each cell line were used: vehicle control, 20 mg/kg/mouse/d glyceollin mixture injection, 0.72 mg estradiol (E2) implant, and E2 implant + 20 mg/kg/mouse/d glyceollin injection. Results: Treatment with glyceollin suppressed E2-stimulated tumor growth of MCF-7 cells (−53.4%) and BG-1 cells (−73.1%) in ovariectomized athymic mice. These tumor-inhibiting effects corresponded with significantly lower E2-induced progesterone receptor expression in the tumors. In contrast to tamoxifen, the glyceollins had no estrogen-agonist effects on uterine morphology and partially antagonized the uterotropic effects of estrogen. Conclusions: These findings identify glyceollins as antiestrogenic agents that may be useful in the prevention or treatment of breast and ovarian carcinoma.

Outpatient radical prostatectomy: impact of standard perineal approach on patient outcome.

PURPOSE As managed care becomes more prevalent, urologists must critically evaluate the economic aspect of and patient satisfaction with urological practice patterns. We have previously reported the advantages of radical perineal prostatectomy, which decreases hospitalization and morbidity, and provides a more rapid return to normal activity, translating into cost savings. We have since evaluated the satisfaction of patients who underwent outpatient radical prostatectomy with and without laparoscopic pelvic lymph node dissection. MATERIALS AND METHODS We evaluated the charts of 250 consecutive patients who underwent outpatient radical perineal prostatectomy with less than 24 hours of hospitalization from 1992 to 1997. Complications, pain management, blood transfusion, and bowel and urinary dysfunction were assessed. Validated quality of life questionnaires were mailed to 200 patients several months postoperatively and a 62% response rate was achieved. RESULTS Mean followup in the series was 30 months. In the perioperative period there were rectal perforation in less than 2% of patients, anastomotic stricture in 3%, perineal fistula in 0.4% and blood transfusion in 11%. Some problems with bowel movements immediately after the procedure, such as diarrhea, constipation or soiled underwear, developed in 17% of patients, of whom up to 20% had had some bowel dysfunction before surgery. In the majority bowel problems resolved in an average of 7.3 weeks. Persistent new onset bowel trouble developed in 9 of the 124 patients (7%). The questionnaire demonstrated persistent significant urinary incontinence in 8 cases (7%). Nerve sparing was attempted in 54 patients, including 22 (41%) who achieve erection sufficient for vaginal penetration and are satisfied with sexual function. Of the patients 17% reported problems after hospital discharge that were mostly related to Foley catheter management. Overall 94.8% of patients were satisfied with treatment. Physical and social/family well-being appeared to be excellent according to the questionnaire. Only 12% of patients would have preferred longer hospitalization. The preferred method of pain control was nonsteroidal anti-inflammatory drugs. CONCLUSIONS Radical perineal prostatectomy is a low morbidity alternative for localized prostate cancer. Outpatient radical perineal prostatectomy may be performed with good patient satisfaction and safety. There appear to be few bowel problems after long-term followup.

Diffusion-weighted MR Imaging of the Placenta in Fetuses with Placental Insufficiency

PURPOSE To evaluate diffusion-weighted magnetic resonance (MR) imaging of the human placenta in fetuses with and fetuses without intrauterine growth restriction (IUGR) who were suspected of having placental insufficiency. MATERIALS AND METHODS The study was approved by the local ethics committee, and written informed consent was obtained. The authors retrospectively evaluated 1.5-T fetal MR images from 102 singleton pregnancies (mean gestation ± standard deviation, 29 weeks ± 5; range, 21-41 weeks). Morphologic and diffusion-weighted MR imaging were performed. A region of interest analysis of the apparent diffusion coefficient (ADC) of the placenta was independently performed by two observers who were blinded to clinical data and outcome. Placental insufficiency was diagnosed if flattening of the growth curve was detected at obstetric ultrasonography (US), if the birth weight was in the 10th percentile or less, or if fetal weight estimated with US was below the 10th percentile. Abnormal findings at Doppler US of the umbilical artery and histopathologic examination of specimens from the placenta were recorded. The ADCs in fetuses with placental insufficiency were compared with those in fetuses of the same gestational age without placental insufficiency and tested for normal distribution. The t tests and Pearson correlation coefficients were used to compare these results at 5% levels of significance. RESULTS Thirty-three of the 102 pregnancies were ultimately categorized as having an insufficient placenta. MR imaging depicted morphologic changes (eg, infarction or bleeding) in 27 fetuses. Placental dysfunction was suspected in 33 fetuses at diffusion-weighted imaging (mean ADC, 146.4 sec/mm(2) ± 10.63 for fetuses with placental insufficiency vs 177.1 sec/mm(2) ± 18.90 for fetuses without placental insufficiency; P < .01, with one false-positive case). The use of diffusion-weighted imaging in addition to US increased sensitivity for the detection of placental insufficiency from 73% to 100%, increased accuracy from 91% to 99%, and preserved specificity at 99%. CONCLUSION Placental dysfunction associated with growth restriction is associated with restricted diffusion and reduced ADC. A decreased ADC used as an early marker of placental damage might be indicative of pregnancy complications such as IUGR. SUPPLEMENTAL MATERIAL http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.10092283/-/DC1.

Effect of Hurricane Katrina on the incidence of acute coronary syndrome at a primary angioplasty center in New Orleans.

BACKGROUND In August 2005, New Orleans was hit by Hurricane Katrina, the costliest natural disaster in US history. Previous studies have shown an increase in acute myocardial infarction (AMI) in the immediate hours to weeks after natural disasters. The goals of our study were to detect any long-term increase in the incidence of AMI after Katrina and to investigate any pertinent contributing factors. METHODS This was a single-center retrospective cohort observational study. Patients admitted with AMI to Tulane Health Sciences Center hospital in the 2 years before Katrina and in the 2 years after the hospital reopened (5 months after Katrina) were identified from hospital records. The 2 groups (pre- and post-Katrina) were compared for prespecified demographic and clinical data. RESULTS In the post-Katrina group, there were 246 admissions for AMI, out of a total census of 11,282 patients (2.18%), as compared with 150 AMI admissions out of a total of 21,229 patients (0.71%) in the pre-Katrina group (P < 0.0001). The post-Katrina group had a significantly higher prevalence of unemployment (P = 0.0003), lack of medical insurance (P < 0.0001), medication noncompliance (P = 0.0001), smoking (P = 0.001), substance abuse (P = 0.03), first-time hospitalization (P < 0.001), local residents rather than visitors affected (P < 0.0001), and people living in temporary housing (P = 0.003). DISCUSSION The role of chronic stress in the pathogenesis of AMI is poorly understood, especially in the aftermath of natural disasters. Our data suggest that Katrina was associated with prolonged loss of employment and insurance, decreased access to preventive health services, and an increased incidence of AMI. In addition, it appears that chronic stress after a natural disaster can be associated with tobacco abuse and medication and therapeutic noncompliance. CONCLUSIONS We found a 3-fold increased incidence of AMI more than 2 years after Hurricane Katrina. Even allowing for the loss of some local hospitals after the disaster, this represents a significant change in overall health of the study population and supports the need for further study into the health effects of chronic stress.

Prospective dual role of mesenchymal stem cells in breast tumor microenvironment.

Breast cancer tissue is a heterogeneous cellular milieu comprising cancer and host cells. The interaction between breast malignant and non-malignant cells takes place in breast tumor microenvironment (TM), and has a crucial role in breast cancer progression. In addition to cellular component of TM, it mainly consists of cytokines released by tumor cells. The tumor-tropic capacity of mesenchymal stem cells (MSCs) and their interaction with breast TM is an active area of investigation. In the present communication, the interplay between the breast resident adipose tissue-derived MSCs (B-ASCs) and breast TM was studied. It was found that a distinct subset of B-ASCs display a strong affinity for conditioned media (CM) from two breast cancer cell lines, MDA-MB 231 (MDA-CM) and MCF-7 (MCF-CM). The expressions of several cytokines including angiogenin, GM-CSF, IL-6, GRO-α and IL-8 in MDA-CM and MCF-CM have been identified. Upon functional analysis a crucial role for GRO-α and IL-8 in B-ASCs migration was detected. The B-ASC migration was found to be via negative regulation of RECK and enhanced expression of MMPs. Furthermore, transcriptome analysis showed that migratory subpopulation express both pro- and anti-tumorigenic genes and microRNAs (miRNA). Importantly, we observed that the migratory cells exhibit similar gene and miRNA attributes as those seen in B-ASCs of breast cancer patients. These findings are novel and suggest that in breast cancer, B-ASCs migrate to the proximity of tumor foci. Characterization of the molecular mechanisms involved in the interplay between B-ASCs and breast TM will help in understanding the probable role of B-ASCs in breast cancer development, and could pave way for anticancer therapies.

Effect of Hurricane Katrina on incidence of acute myocardial infarction in New Orleans three years after the storm.

To detect a long-term increase in the incidence of acute myocardial infarction (AMI) after Hurricane Katrina and to investigate the pertinent contributing factors, we conducted a single-center retrospective cohort observational study. The patients admitted with AMI to Tulane University Hospital in the 2 years before Katrina and the 3 years after the hospital reopened were identified from the hospital medical records. The pre- and post-Katrina groups were compared for prespecified demographic and clinical data. In the 3-year post-Katrina group, 418 admissions (2.0%) for AMI occurred of a total census of 21,092 patients compared to 150 (0.7%) of a census of 21,079 in the 2-year pre-Katrina group (p <0.0001). The post-Katrina group had a greater prevalence of unemployment (p <0.0001), lack of medical insurance (p <0.001), smokers (p <0.01), medical noncompliance (p <0.0001), first-time hospitalizations (p <0.001), history of coronary artery disease (p <0.01), multiple vessel disease (p <0.05), and percutaneous coronary interventions (p <0.0001). The mean age of onset of AMI decreased from 62 years before Katrina to 59 years after Katrina (p <0.05), and a significantly greater percentage of patients were men (p <0.05). No significant differences were found between the two groups in terms of race, substance abuse, and a history of hypertension or diabetes mellitus. Our data suggest that chronic stress after natural disasters may significantly affect cardiovascular risk factors such as tobacco abuse and increase medical noncompliance. In conclusion, our data is consistent with a significant change in the overall health of the population and support the need for additional study into the health effects of chronic stress after natural disasters.

Magnetic resonance angiography in infrapopliteal arterial disease: prospective comparison of 1.5 and 3 Tesla magnetic resonance imaging.

Purpose:To prospectively determine the accuracy of 1.5 Tesla (T) and 3 T magnetic resonance angiography (MRA) versus digital subtraction angiography (DSA) in the depiction of infrageniculate arteries in patients with symptomatic peripheral arterial disease. Patients and Methods:A prospective 1.5 T, 3 T MRA, and DSA comparison was used to evaluate 360 vessel segments in 10 patients (15 limbs) with chronic symptomatic peripheral arterial disease. Selective DSA was performed within 30 days before both MRAs. The accuracy of 1.5 T and 3 T MRA was compared with DSA as the standard of reference by consensus agreement of 2 experienced readers. Signal-to-noise ratios (SNR) and signal-difference-to-noise ratios (SDNRs) were quantified. Results:No significant difference in overall image quality, sufficiency for diagnosis, depiction of arterial anatomy, motion artifacts, and venous overlap was found comparing 1.5 T with 3 T MRA (P > 0.05 by Wilcoxon signed rank and as by Cohen k test). Overall sensitivity of 1.5 and 3 T MRA for detection of significant arterial stenosis was 79% and 82%, and specificity was 87% and 87% for both modalities, respectively. Interobserver agreement was excellent k > 0.8, P < 0.05) for 1.5 T as well as for 3 T MRA. SNR and SDNR were significantly increased using the 3 T system (average increase: 36.5%, P < 0.032 by t test, and 38.5%, P < 0.037 respectively). Conclusions:Despite marked improvement of SDNR, 3 T MRA does not yet provide a significantly higher accuracy in diagnostic imaging of atherosclerotic lesions below the knee joint as compared with 1.5 T MRA.

Global Bidirectional Transcription of the Epstein-Barr Virus Genome during Reactivation

ABSTRACT Epstein-Barr virus (EBV) reactivation involves the ordered induction of approximately 90 viral genes that participate in the generation of infectious virions. Using strand-specific RNA-seq to assess the EBV transcriptome during reactivation, we found extensive bidirectional transcription extending across nearly the entire genome. In contrast, only 4% of the EBV genome is currently bidirectionally annotated. Most of the newly identified transcribed regions show little evidence of coding potential, supporting noncoding roles for most of these RNAs. Based on previous cellular long noncoding RNA size calculations, we estimate that there are likely hundreds more EBV genes expressed during reactivation than was previously known. Limited 5′ and 3′ rapid amplification of cDNA ends (RACE) experiments and findings of novel splicing events by RNA-seq suggest that the complexity of the viral genome during reactivation may be even greater. Further analysis of antisense transcripts at some of the EBV latency gene loci showed that they are “late” genes, they are nuclear, and they tend to localize in areas of the nucleus where others find newly synthesized viral genomes. This raises the possibility that these transcripts perform functions such as new genome processing, stabilization, organization, etc. The finding of a significantly more complex EBV transcriptome during reactivation changes our view of the viral production process from one that is facilitated and regulated almost entirely by previously identified viral proteins to a process that also involves the contribution of a wide array of virus encoded noncoding RNAs. IMPORTANCE Epstein-Barr virus (EBV) is a herpesvirus that infects the majority of the worlds population, in rare cases causing serious disease such as lymphoma and gastric carcinoma. Using strand-specific RNA-seq, we have studied viral gene expression during EBV reactivation and have discovered hundreds more viral transcripts than were previously known. The finding of alternative splicing and the prevalence of overlapping transcripts indicate additional complexity. Most newly identified transcribed regions do not encode proteins but instead likely function as noncoding RNA molecules which could participate in regulating gene expression, gene splicing or even activities such as viral genome processing. These findings broaden the scope of what we need to consider to understand the viral manufacturing process. As more detailed studies are undertaken they will likely change the way we view this process as a whole.

MR Angiography of Infrapopliteal Arteries in Patients with Peripheral Arterial Occlusive Disease by Using Gadofosveset at 3.0 T: Diagnostic Accuracy Compared with Selective DSA

PURPOSE To prospectively compare the diagnostic accuracy of steady-state, high-spatial-resolution magnetic resonance (MR) angiography of the lower leg, performed with a blood pool contrast agent, with selective digital subtraction angiography (DSA) as the reference standard in patients with symptomatic peripheral arterial disease. MATERIALS AND METHODS Local ethics committee approval and written informed consent were obtained. In a nonrandomized trial, selective DSA and MR angiography were performed at 3.0 T with a blood pool contrast agent on 22 calves in 20 patients (mean age, 69.4 years +/- 11.3 [standard deviation]), 16 men (mean age, 67.8 years +/- 12.4) and four women (mean age, 75.6 years +/- 3.6 years), to evaluate 352 arterial segments. DSA and MR angiography were performed within 24 hours of each other and directly compared by three experienced, blinded radiologists by using high-spatial-resolution steady-state MR angiograms. Consensus reading for both DSA and MR angiography served as the reference standard. RESULTS MR angiography was successful and occurred without serious adverse events in all patients. Seven significantly stenosed and 40 occluded segments were rated equally in both modalities. In three cases, the tibial arteries were shown to be occluded or significantly stenosed at DSA but appeared normal or significantly stenosed at MR angiography. The respective average segment sensitivity, specificity, and accuracy were 98.3% (59 of 60), 98% (113.7 of 116), and 98.1% (172.7 of 176) for DSA and 100% (60 of 60), 100% (116 of 116), and 100% (176 of 176) for MR angiography. Steady-state MR angiography was especially useful for the distal peroneal artery and the proximal anterior tibial artery. CONCLUSION MR angiography performed with blood pool agents has an accuracy comparable with that of selective DSA in the lower leg but with less risk involved. Steady-state imaging performed with blood pool agents facilitates evaluation of MR angiography of infrapopliteal arteries.

Anterior and posterior reconstruction technique and its impact on early return of continence after robot-assisted radical prostatectomy.

BACKGROUND AND PURPOSE Urinary incontinence is a significant cause of morbidity after robot-assisted radical prostatectomy (RARP). Several techniques have been developed to improve continence rates. In this study, we compared the continence rates of patients who underwent RARP with total reconstruction and without reconstruction. PATIENTS AND METHODS Between March 2005 and September 2009, 245 patients underwent RARP at our institution. The initial 120 patients (control group) underwent standard RARP without reconstruction and the last 125 patients (reconstruction group) underwent a total reconstruction technique, which included an anterior and posterior reconstruction. Patients were followed for 1, 4, 12, 24, 36, and 52 weeks after the operation. Continence was defined with strict criteria-no usage of pads and no leakage of urine. RESULTS In the reconstruction group, the continence rates at, 1, 4, 12, 24, 36, and 52 weeks postoperatively were 71%, 72%, 80%, 84%, 86%, and 91%, respectively; in the control group, the continence rates were 23%, 49%, 76%, 80%, 85%, and 88%, respectively. CONCLUSION The overall continence rates were similar in both groups at 52 weeks of follow-up. Patients in the total reconstruction group, however, had higher early continence rates compared with patients in the control group. The total reconstruction procedure is an efficient way to achieve an early return to continence.