by
Samir K. Ballas;
Muge R. Kesen;
Morton F. Goldberg;
Gerard A. Lutty;
Carlton Dampier;
Ifeyinwa Osunkwo;
Winfred C. Wang;
Carolyn Hoppe;
Ward Hagar;
Deepika S. Darbari;
Punam Malik
The sickle hemoglobin is an abnormal hemoglobin due to point mutation (GAG → GTG) in exon 1 of the globin gene resulting in the substitution of glutamic acid by valine at position 6 of the globin polypeptide chain. Although the molecular lesion is a single-point mutation, the sickle gene is pleiotropic in nature causing multiple phenotypic expressions that constitute the various complications of sickle cell disease in general and sickle cell anemia in particular. The disease itself is chronic in nature but many of its complications are acute such as the recurrent acute painful crises (its hallmark), acute chest syndrome, and priapism. These complications vary considerably among patients, in the same patient with time, among countries and with age and sex. To date, there is no well-established consensus among providers on the management of the complications of sickle cell disease due in part to lack of evidence and in part to differences in the experience of providers. It is the aim of this paper to review available current approaches to manage the major complications of sickle cell disease. We hope that this will establish another preliminary forum among providers that may eventually lead the way to better outcomes.
In recent years, evidence has increased that asthma predisposes to complications of sickle cell disease (SCD), such as pain crises, acute chest syndrome, pulmonary hypertension, and stroke, and is associated with increased mortality. An obstructive pattern of pulmonary function, along with a higher-than-expected prevalence of airway hyper-responsiveness (AHR) when compared to the general population, has led some researchers to suspect that underlying hemolysis may contribute to the development of a pulmonary disease similar to asthma in patients with SCD. While the pathophysiologic mechanism in atopic asthma involves up-regulation of Th2 cytokines, mast cell- and eosinophil-driven inflammation, plus increased activity of inducible nitric oxide synthase (iNOS) and arginase in airway epithelium resulting in obstructive changes and AHR, the exact mechanisms of AHR, obstructive and restrictive lung disease in SCD is unclear. It is known that SCD is associated with a proinflammatory state and an enhanced inflammatory response is seen during vaso-occlusive events (VOE). Hemolysis-driven acute-on-chronic inflammation and dysregulated arginine-nitric oxide metabolism are potential mechanisms by which pulmonary dysfunction could occur in patients with SCD. In patients with a genetic predisposition of atopic asthma, these changes are probably more severe and result in increased susceptibility to sickle cell complications. Early recognition and aggressive management of asthma based on established National Institutes of Health asthma guidelines is recommended in order to minimize morbidity and mortality.
by
Ziad Abdeen;
Radwan Qasrawi;
Jongbae Heo;
Bo Wu;
Jacob Shpund;
Arye Vanger;
Geula Sharf;
Tamar Moise;
Shmuel Brenner;
Khaled Nassar;
Rami Saleh;
Qusai M. Al-Mahasneh;
Jeremy Sarnat;
James J. Schauer
Ambient fine particulate matter (PM2.5) samples were collected from January to December 2007 to investigate the sources and chemical speciation in Palestine, Jordan, and Israel. The 24-h PM2.5samples were collected on 6-day intervals at eleven urban and rural sites simultaneously. Major chemical components including metals, ions, and organic and elemental carbon were analyzed. The mass concentrations of PM2.5across the 11 sites varied from 20.6 to 40.3 g/m3, with an average of 28.7 g/m 3. Seasonal variation of PM2.5concentrations was substantial, with higher average concentrations (37.3 g/m3) in the summer (April-June) months compared to winter (October-December) months (26.0 g/m3) due mainly to high contributions of sulfate and crustal components. PM2.5 concentrations in the spring were greatly impacted by regional dust storms. Carbonaceous mass was the most abundant component, contributing 40% to the total PM2.5mass averaged across the eleven sites. Crustal components averaged 19.1% of the PM2.5mass and sulfate, ammonium, and nitrate accounted for 16.2%, 6.4%, and 3.7%, respectively, of the total PM2.5 mass. The results of this study demonstrate the need to better protect the health and welfare of the residents on both sides of the Jordan River in the Middle East.
Endometriosis is characterized by endometrial-like tissue outside the uterus, primarily on the pelvic peritoneum, ovaries, and rectovaginal septum, and, in rare cases, within the urinary tract (1-3%). Although endometriosis is a benign condition, malignant transformation of endometriosis is a well-described phenomenon. Malignancies arising in endometriosis are uncommon at extragonadal pelvic sites. A case of endometrioid adenocarcinoma in the native ureter of a postmenopausal renal transplant patient presented with painless gross hematuria and hydroureteronephrosis. The patient had a history of total abdominal hysterectomy and bilateral salpingo-oophrectomy 14 years prior for menorrhagia and had since been on unopposed estrogen replacement therapy. Workup revealed a filling defect in the native left mid-ureter secondary to a large 2.5-cm ureteral tumor. Endoscopic biopsies of the native left ureteral mass showed endometrioid adenocarcinoma, grade II-III. The patient ultimately underwent an open native left nephroureterectomy and temporary diverting colostomy. Final pathology confirmed endometrioid adenocarcinoma, grade II-III, arising in a background of endometriosis with negative perirectal lymph nodes. This case of ureteral endometrioid adenocarcinoma highlights the importance of obtaining a careful history and maintaining a high index of suspicion for malignant degeneration, especially in the context of hyperestrogenism.
Prostate cancer represents a model site for advances in understanding inter- and intrafraction motion for radiotherapy. In this study, we examined the correlation of the electromagnetic transponder system/Calypso® 4D Localization System with conventional on-board imaging (OBI) using kilovoltage imaging. Initially using a quality assurance (QA) phantom and subsequently using data of seven patients, the vector distances between Calypso- and OBI-recorded shifts were compared using the t-test. For the 30 phantom measurements, the average differences between the measured Calypso offset and the calculated OBI shift were 0.4 ± 0.4, 0.2 ± 0.3, and 0.4 ± 0.3 mm in the lateral, longitudinal, and vertical directions, respectively (p = 0.73, p = 0.91, and p = 0.99, respectively), and the average difference vector for all sessions was 0.8 ± 0.4 mm. For the 259 patient measurements, the average differences between the measured Calypso offset and the calculated OBI shift were 0.7 ± 0.5, 1.1 ± 0.9, and 1.2 ± 0.9 mm in the lateral, longitudinal, and vertical directions, respectively (p = 0.45, p = 0.28, and p = 0.56, respectively), and the average difference vector for all sessions was 2.1 ± 1.0 mm. Our results demonstrated good correlation between Calypso and OBI. While other studies have explored the issue of Calypso/OBI correlation, our analysis is unique in our use of phantom validation and in our performing the patient analysis on an initial population prior to routine setup using Calypso without OBI. Implications for Calypso's role as a QA tool are discussed.
HIV infection is associated with increased incidence of malignancies, such as lymphomas and testicular cancers. We reviewed the relationship between HIV infection and prostate cancer in a contemporary series of prostate biopsy patients. The study is a retrospective analysis of consecutive prostate biopsies performed at a VA Medical Center. The indications for performing a prostate biopsy included an abnormal digital rectal examination and/or an elevated PSA. Patients were categorized according to their HIV status, biopsy results, and various demographic and clinical characteristics. Univariate and multivariate analyses compared distributions of HIV status, and various clinical and demographic characteristics. The adjusted measures of association between HIV status and positive biopsy were expressed as odds ratios (ORs) and corresponding 95% confidence intervals (CI). The likelihood of positive biopsy was significantly higher among 18 HIV-positive patients compared to patients with negative HIV tests (adjusted OR = 3.9; 95% CI: 1.3-11.5). In analyses restricted to prostate cancer patients, HIVpositive patients were not different from the remaining group with respect to their prostate cancer stage, PSA level, PSA velocity, PSA density, or Gleason grade. There is an association between HIV infection and prostate biopsy positive for carcinoma in a population referred for urologic workup. Further confirmation of this association by prospective studies may impact the current screening practices in HIV patients.
Utilization of nuclear bone scans for staging newly diagnosed prostate cancer has decreased dramatically due to PSA-driven stage migration. The current criteria for performing bone scans are based on limited historical data. This study evaluates serum PSA and Gleason grade in predicting positive scans in a contemporary large series of newly diagnosed prostate cancer patients. Eight hundred consecutive cases of newly diagnosed prostate cancer over a 64-month period underwent a staging nuclear scan. All subjects had histologically confirmed cancer. The relationship between PSA, Gleason grade, and bone scan was examined by calculating series of crude, stratified, and adjusted odds ratios with corresponding 95% confidence intervals. Four percent (32/800) of all bone scans were positive. This proportion was significantly lower in patients with Gleason score ≤7 (1.9%) vs. Gleason score ≥8 (18.8%, p < 0.001). Among patients with Gleason score ≤7, the rate of positive bones scans was 70-fold higher when the PSA was > 30 ng/ml compared to ≤30 ng/ml (p < 0.001). For Gleason score ≥8, the rate was significantly higher (27.9 vs. 0%) when PSA was > 10 ng/ml compared to ≤10 ng/ml (p = 0.002). The combination of Gleason score and PSA enhances predictability of bone scans in newly diagnosed prostate cancer patients. The PSA threshold for ordering bone scans should be adjusted according to Gleason score. F or patients with Gleason scores ≤7, we recommend a bone scan if the PSA is > 30 ng/ml. However, for patients with a high Gleason score (8-10), we recommend a bone scan if the PSA is > 10 ng/ml.
Seaweed is one of the largest producers of biomass in marine environment and is a rich arsenal of active metabolites and functional ingredients with valuable beneficial health effects. Being a staple part of Asian cuisine, investigations on the crude extracts of Phaeophyceae or brown algae revealed marked antitumor activity, eliciting a variety of research to determine the active ingredients involved in this potential. The sulfated polysaccharide of fucoidan and carotenoid of fucoxanthin were found to be the most important active metabolites of brown algae as potential chemotherapeutic or chemopreventive agents. This review strives to provide detailed account of all current knowledge on the anticancer and antitumor activity of fucoidan and fucoxanthin as the two major metabolites isolated from brown algae.
Combining multiple microarray datasets increases sample size and leads to improved reproducibility in identification of informative genes and subsequent clinical prediction. Although microarrays have increased the rate of genomic data collection, sample size is still a major issue when identifying informative genetic biomarkers. Because of this, feature selection methods often suffer from false discoveries, resulting in poorly performing predictive models. We develop a simple meta-analysis-based feature selection method that captures the knowledge in each individual dataset and combines the results using a simple rank average. In a comprehensive study that measures robustness in terms of clinical application (i.e., breast, renal, and pancreatic cancer), microarray platform heterogeneity, and classifier (i.e., logistic regression, diagonal LDA, and linear SVM), we compare the rank average meta-analysis method to five other meta-analysis methods. Results indicate that rank average meta-analysis consistently performs well compared to five other meta-analysis methods.
Mixed epithelial and stromal tumors (MESTs) of the kidney are rare renal neoplasms characterized by mixed cystic and solid components. These tumors are typically present in middle-aged women as a flank mass, or as a cause of flank pain or hematuria. We outline the case of an older male who presented with an enlarging abdominal mass causing symptoms that suggested a partial small bowel obstruction. Management of the patient and a brief review are discussed.