Heather A. Young

Thimerosal exposure in infants and neurodevelopmental disorders: An assessment of computerized medical records in the Vaccine Safety Datalink

The study evaluated possible associations between neurodevelopmental disorders (NDs) and exposure to mercury (Hg) from Thimerosal-containing vaccines (TCVs) by examining the automated Vaccine Safety Datalink (VSD). A total of 278,624 subjects were identified in birth cohorts from 1990-1996 that had received their first oral polio vaccination by 3 months of age in the VSD. The birth cohort prevalence rate of medically diagnosed International Classification of Disease, 9th revision (ICD-9) specific NDs and control outcomes were calculated. Exposures to Hg from TCVs were calculated by birth cohort for specific exposure windows from birth-7 months and birth-13 months of age. Poisson regression analysis was used to model the association between the prevalence of outcomes and Hg doses from TCVs. Consistent significantly increased rate ratios were observed for autism, autism spectrum disorders, tics, attention deficit disorder, and emotional disturbances with Hg exposure from TCVs. By contrast, none of the control outcomes had significantly increased rate ratios with Hg exposure from TCVs. Routine childhood vaccination should be continued to help reduce the morbidity and mortality associated with infectious diseases, but efforts should be undertaken to remove Hg from vaccines. Additional studies should be conducted to further evaluate the relationship between Hg exposure and NDs.

Small Bowel Obstruction: Conservative vs. Surgical Management

PURPOSEThe aim of this study was to assess incidence, risk factors, and recurrence rates for conservative and surgical management of small bowel obstruction.METHODSRetrospective chart review was conducted of 329 patients accounting for 487 admissions with small bowel obstruction. Data were obtained from the institutional database and patient charts. Patients with early recurrent small bowel obstruction had prior operations or hospitalization with conservative therapy for small bowel obstruction, then had a hospital stay >10 days following abdominal surgery because of obstruction or required readmission for small bowel obstruction within 30 days. Patients treated for prior small bowel obstruction and then readmitted after 30 days for a recurrent small bowel obstruction were classified as having late recurrent small bowel obstruction.RESULTSA total of 329 patients with a diagnosis of small bowel obstruction were identified. At index admission, 43 percent (142) were successfully treated conservatively, whereas 57 percent (187) failed conservative treatment and underwent surgery. Overall, there were eight early deaths, four in each group (2.8 percent conservative vs. 2.1 percent surgical; no significant difference). The frequency of recurrence for those treated nonoperatively was 40.5 percent compared with 26.8 percent for patients treated operatively (P < 0.009). Patients treated without operation had a significantly shorter time to recurrence (mean, 153 vs. 411 days; P < 0.004) and had fewer hospital days for their index small bowel obstruction (4.9 vs. 12.0 days; P < 0.0001). Two hundred one (63 percent) patients had abdominal surgery and 119 (37 percent) patients had no prior abdominal surgery before developing a small bowel obstruction. Previous abdominal operations by procedure type were colorectal surgery (34 percent), gynecologic surgery (28 percent), exploratory laparotomy (20 percent), appendectomy (14 percent), cholecystectomy (12 percent), herniorraphy (8 percent), and gastric bypass (5 percent). The mean time interval between initial procedure and index small bowel obstruction was 1.3 years for gastric bypass, 6.1 years for herniorraphy, 7.8 years for exploratory laparotomy, 8 years for cholecystectomy, 8.4 years for colorectal surgery, 11.8 years for gynecologic surgery, and 22.5 years for appendectomy. There was no significant difference between early and late recurrent small bowel obstruction in patients treated nonoperatively or operatively, regardless of prior history of abdominal surgery. Logistic regression analysis failed to identify any specific risk factors that were predictors of the success of conservative or surgical management.CONCLUSIONSOperatively treated patients had a lower frequency of recurrence and a longer time interval to recurrence; however, they also had a longer hospital stay than that of patients treated nonoperatively. There was no significant difference in treatment type or in incidence or type of prior surgery among patients with early and late small bowel obstruction. None of the variables analyzed in this study were significant predictors of the success of a particular treatment.

Inhibition of Prostate Cancer Growth by Muscadine Grape Skin Extract and Resveratrol through Distinct Mechanisms

The phytochemical resveratrol contained in red grapes has been shown to inhibit prostate cancer cell growth, in part, through its antioxidant activity. Muscadine grapes contain unique phytochemical constituents compared with other grapes and are potentially a source for novel compounds with antitumor activities. We compared the antitumor activities of muscadine grape skin extract (MSKE), which we show contains no resveratrol, with that of resveratrol using primary cultures of normal prostate epithelial cells (PrEC) and the prostate cancer cell lines RWPE-1, WPE1-NA22, WPE1-NB14, and WPE1-NB26, representing different stages of prostate cancer progression. MSKE significantly inhibited tumor cell growth in all transformed prostate cancer cell lines but not PrEC cells. Prostate tumor cell lines, but not PrEC cells, exhibited high rates of apoptosis in response to MSKE through targeting of the phosphatidylinositol 3-kinase-Akt and mitogen-activated protein kinase survival pathways. The reduction in Akt activity by MSKE is mediated through a reduction in Akt transcription, enhanced proteosome degradation of Akt, and altered levels of DJ-1, a known regulator of PTEN. In contrast to MSKE, resveratrol did not induce apoptosis in this model but arrested cells at the G(1)-S phase transition of the cell cycle associated with increased expression of p21 and decreased expression of cyclin D1 and cyclin-dependent kinase 4 proteins. These results show that MSKE and resveratrol target distinct pathways to inhibit prostate cancer cell growth in this system and that the unique properties of MSKE suggest that it may be an important source for further development of chemopreventive or therapeutic agents against prostate cancer.

HIV-positive patients with anal carcinoma have poorer treatment tolerance and outcome than HIV-negative patients

PURPOSE: Anal carcinoma is being found in HIV-positive patients with increasing frequency. Most patients are treated with combined chemotherapy and radiation. It was our impression that HIV-positive patients do not fare as well as HIV-negative patients in terms of both response to and tolerance of therapy. METHODS: To test this hypothesis, we reviewed our experience with anal carcinoma and compared HIV-positive to HIV-negative patients by age, gender, sexual orientation, stage at diagnosis, treatment rendered, response to treatment, tolerance, and survival. From 1985 to 1998, 98 patients with anal neoplasms were treated. Seventy-three patients had invasive squamous-cell carcinoma (including cloacogenic carcinoma), and this cohort was analyzed. Thirteen patients were HIV positive and 60 were HIV negative. RESULTS: The HIV-positive and HIV-negative groups differed significantly by age (42vs. 62 years,P<0.001), male gender (92vs. 42 percent,P<0.001), and homosexuality (46vs. 15 percent,P<0.05). There were no differences by stage at diagnosis or radiation dose received. Acute treatment major toxicity differed significantly (HIV positive 80 percentvs. HIV negative 30 percent;P<0.005). Only 62 percent of HIV-positive patients were rendered disease free after initial therapyvs. 85 percent of HIV-negative patients (P=0.11). Median time to cancer-related death was 1.4vs. 5.3 years (P<0.05). A survival model did not show age, gender, stage, or treatment to be independent predictors. CONCLUSION: We found that HIV-positive patients with anal carcinoma seem to be a different population from HIV-negative patients by age, gender, and sexual orientation. They have a poorer tolerance for combined therapy and a shorter time to cancer-related death. A strong trend to poorer initial response rate was also seen. These results suggest that the treatment of HIV-positive patients with anal carcinoma needs to be reassessed.

Thrombosed external hemorrhoids: outcome after conservative or surgical management.

PURPOSE:Few data exist on the actual recurrence rates of thrombosed external hemorrhoids. We wished to determine the incidence of recurrence, intervals to recurrence, and factors predicting recurrence of thrombosed external hemorrhoids after conservative or surgical management.METHODS:Two hundred and thirty-one consecutive patients with thrombosed external hemorrhoids treated from 1990 to 2002 were identified. Recurrence was defined as complete resolution of the index lesion with subsequent return of a thrombosed external hemorrhoid and did not include patients with chronic symptoms. Data were gathered retrospectively. Multiple potential risk factors were reviewed.RESULTS:The index thrombosed external hemorrhoid was managed conservatively in 51.5 percent of cases and surgically in 48.5 percent. There were no differences between groups in gender, age, or race, and 44.5 percent of all patients had a prior history of thrombosed external hemorrhoid. A prior history was less common in the conservative group than in the surgical group (38.1 percent vs. 51.3 percent; P < 0.05). The frequency of pain or bleeding as the primary complaint was higher in the surgical group (P < 0.001 and P < 0.002). In addition, the surgical group was more likely to report all three symptoms of pain, bleeding, and a lump (P < 0.005). Mean follow-up was 7.6 months, with the range extending to 7 years. Time to symptom resolution averaged 24 days in the conservative group vs. 3.9 days in the surgical group (P < 0.0001). The overall incidence to recurrence was 15.6 percent—80.6 percent in the conservative group vs. 19.4 percent in the surgical group. The rate of recurrence in the conservative group was 25.4 percent (4/29; 14 percent were excised) whereas only 6.3 percent of the surgical patients had recurrence (P < 0.0001). Mean time to recurrence was 7.1 months in the conservative group vs. 25 months in the surgical group (P < 0.0001). Survival analysis for time to recurrence of thrombosed external hemorrhoid indicated that time to recurrence was significantly longer for the surgical group (P < 0.0001). Logistic regression analysis of multiple factors (including diverticular disease, constipation, straining, benign prostatic hypertrophy, diarrhea, skin tags, history of travel, anoreceptive sex, anal fissures, internal hemorrhoids, and obesity) was performed to determine the outcome of each group. None of these variables were significant predictors of recurrence.CONCLUSIONS:Patients whose initial presentation was pain or bleeding with or without a lump were more like to be treated surgically. Surgically treated patients had a lower frequency of recurrence and a longer time interval to recurrence than conservatively treated patients. None of the variables analyzed were significant predictors of a particular treatment, except for a prior history of thrombosed external hemorrhoids, which may represent patient choice. Although most patients treated conservatively will experience resolution of their symptoms, excision of thrombosed external hemorrhoids results in more rapid symptom resolution, lower incidence of recurrence, and longer remission intervals.

Breast-Specific Gamma Imaging with 99mTc-Sestamibi and Magnetic Resonance Imaging in the Diagnosis of Breast Cancer—A Comparative Study

Abstract:  The purpose of this study was to compare the sensitivity and specificity of breast‐specific gamma imaging (BSGI) using a high‐resolution breast‐specific gamma camera and magnetic resonance imaging (MRI) in patients with indeterminate breast findings. Twenty‐three women with an indeterminate breast finding that required BSGI and MRI as deemed necessary by the interpreting radiologist or referring physician were included. MRI was performed on a GE 1.5T scanner and BSGI was performed on a Dilon high‐resolution breast‐specific gamma camera. All imaging findings were correlated with pathologic diagnosis. Thirty‐three indeterminate lesions were evaluated in the study. There were a total of nine pathologically confirmed cancers. There was no statistically significant difference in sensitivity of cancer detection between BSGI and MRI. BSGI demonstrated a greater specificity than MRI, 71% and 25%, respectively. BSGI has equal sensitivity and greater specificity than MRI for the detection of breast cancer.

Evidence for a Deployment-Related Gulf War Syndrome by Factor Analysis

Abstract To identify a syndrome unique to Gulf War veterans, the authors applied an exploratory factor analysis to the 47-symptom correlation matrix of 10,423 Gulf War and 8,960 non-Gulf War veteran respondents. A separate factor analysis was performed for Gulf War and non-Gulf War veterans, and the resulting 6 factors were compared between the 2 groups. Five of the factors were very similar in the 2 groups; however, 1 of the factors in the Gulf War group, but not the non-Gulf War group, contained a cluster of symptoms consistent with neurological impairment. Symptoms specific to this factor were blurred vision, loss of balance/dizziness, tremors/shaking, and speech difficulty. The Gulf War veterans who had all of the aforementioned symptoms (n = 277) also reported exposures to several putative risk factors at a rate 3 or more times higher than other Gulf War veterans. This finding suggests a possible syndrome related to Gulf War deployment, which requires objective supporting clinical evidence.

Angiogenic biomarkers for prediction of maternal and neonatal complications in suspected preeclampsia

Objective: To determine if maternal serum angiogenic factors predict maternal and neonatal complications in women presenting to an acute care setting with suspected preeclampsia. Study design: Maternal serum samples were prospectively collected from women with suspected preeclampsia at the time of initial presentation to hospital triage with signs or symptoms of preeclampsia. Soluble fms-like tyrosine kinase-1 (sFlt1), placental growth factor (PlGF), and soluble endoglin (sEng) were measured by ELISA. The primary outcome was a composite of maternal and neonatal complications. Results: Of 276 women with suspected preeclampsia, 78 developed maternal or neonatal complications. Among women presenting prior to 37 weeks gestation, sFlt1, PlGF, and sEng were significantly different in women who developed maternal and neonatal complications as compared to women without complications. Higher levels of sFlt1, sEng, and the sFlt1:PlGF ratio were associated with an increased odds of complications among women presenting prior to 37 weeks. A multivariable model combining the sFlt1:PlGF ratio with clinical variables was more predictive of complications (AUC 0.91, 95% CI 0.85–0.97) than a model using clinical variables alone (AUC 0.82, 95% CI 0.79–0.90). Conclusion: Angiogenic biomarkers associate with maternal and neonatal complications in women with suspected preeclampsia, and may be useful for risk stratification.

Interpretation of Remotely Downloaded Pocket-Size Cardiac Ultrasound Images on a Web-Enabled Smartphone: Validation Against Workstation Evaluation

BACKGROUND Pocket-size ultrasound has increased echocardiographic portability, but expert point-of-care interpretation may not be readily available. The aim of this study was to test the hypothesis that remote interpretation on a smartphone with dedicated medical imaging software can be as accurate as on a workstation. METHODS Eighty-nine patients in a remote Honduran village underwent echocardiography by a nonexpert using a pocket-size ultrasound device. Images were sent for verification of point-of-care diagnosis to two expert echocardiographers in the United States reading on a workstation. Studies were then anonymized, randomly ordered, and reinterpreted on a smartphone with a dedicated, Health Insurance Portability and Accountability Act-compliant application. Point-of-care diagnosis was considered accurate if any abnormal finding was matched and categorized at the same level of severity (mild, moderate, or severe) by either expert interpretation. RESULTS The mean age was 54 ± 23 years, and 57% of patients were women. The most common indications for echocardiography were arrhythmia (33%), cardiomyopathy (28%), and syncope (15%). Using the workstation, point-of-care diagnoses were changed in 38% of cases by expert overread (41% left ventricular function correction, 38% valvulopathy correction, 18% poor image quality). Expert interobserver agreement was excellent at 82%, with a Cohens κ value of 0.82 (95% confidence interval, 0.70-0.94). Intraobserver agreement comparing interpretations on workstations and smartphones was 90%, with a Cohens κ value of 0.86 (95% confidence interval, 0.76-0.97), signifying excellent intertechnology agreement. CONCLUSIONS Remote expert echocardiographic interpretation can provide backup support to point-of-care diagnosis by nonexperts when read on a dedicated smartphone-based application. Mobile-to-mobile consultation may improve access in previously inaccessible locations to accurate echocardiographic interpretation by experienced cardiologists.

Perineal talc exposure and epithelial ovarian cancer risk in the Central Valley of California

Perineal talc use has been suggested as a possible risk factor for ovarian cancer based on its structural similarity to asbestos, a known human carcinogen. A population‐based epidemiologic case‐control study of epithelial ovarian cancer (EOC) was conducted in 22 counties of Central California that comprise the reporting area for 2 regional cancer registries. Telephone interviews were conducted with 256 cases diagnosed in the years 2000–2001 and 1,122 controls frequency‐matched on age and ethnicity. The interview obtained information on demographic factors, menstrual and reproductive experience, exogenous hormone use, surgical history and family history of cancer. Questions on perineal talc use included frequency of use, duration of use and specific years when talc was used. Multivariate‐adjusted odds ratio (OR) and 95% confidence intervals (CI) were derived from unconditional logistic regression. The OR for ever use of talc was 1.37 (CI = 1.02–1.85) compared to never users. However, no dose response association was found. Tubal ligation (TL) modified the effect of talc on EOC such that women with TL had an OR of 0.88 (CI = 0.46–1.68) associated with perineal talc use, whereas women with no TL had an OR of 1.54 (CI = 1.10–2.16). Talc use and EOC risk was highest in women with serous invasive tumors (OR = 1.77; CI = 1.12–2.81). This study provides some support for the hypothesis that perineal talc use is associated with an increased risk of EOC.