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Urologist
16 years of experience
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Education ?

Medical School Score
Stony Brook University (1994)
  • Currently 2 of 4 apples

Awards & Distinctions ?

Associations
American Board of Urology
American Urological Association

Affiliations ?

Dr. Sherwood is affiliated with 4 hospitals.

Hospital Affilations

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  • Main Line Hospital Lankenau
    Urology
    100 E Lancaster Ave, Wynnewood, PA 19096
    • Currently 1 of 4 crosses
  • Veterans Affairs Hospital
  • M L Hospital, Inc Lankenau
  • Lankenau Hospital - On staff since 2006
  • Publications & Research

    Dr. Sherwood has contributed to 45 publications.
    Title The Diagnosis and Treatment of Urethral Recurrence After Radical Cystectomy.
    Date November 2006
    Journal Urologic Oncology
    Excerpt

    OBJECTIVE: To illustrate the problem of urethral recurrence of transitional cell carcinoma (TCC) after radical cystectomy, and define surveillance and treatment algorithms. METHODS: There are 6 unique cases of urethral tumor recurrence presented, and current relevant literature is reviewed. Three risk groups are defined based on the likelihood of urethral recurrence. Surveillance and treatment options are delineated. RESULTS: Although the incidence of recurrent tumor in the urethra is low, the prevalence is increasing because of improvements in bladder cancer survival and the fact that the urethra is retained more often for orthotopic urinary diversion. Patients can be categorized as low, intermediate, and high risk based on the pathologic finding of degree of prostatic involvement by the initial tumor. CONCLUSION: Based on limited available literature, it appears that surveillance strategies range from observation alone to more invasive monitoring that includes urethral wash cytology and urethroscopy. Treatment options include local resection, intraurethral agents, and complete urethrectomy. A surveillance algorithm based on risk for recurrence and a treatment algorithm based on histopathologic risk factors of the recurrent tumor are proposed. This problem will assume increasing importance in the future.

    Title Efficacy of High Dose Per Fraction Radiation for Implanted Human Prostate Cancer in a Nude Mouse Model.
    Date June 2006
    Journal The Journal of Urology
    Excerpt

    PURPOSE: SBRT is a new therapeutic paradigm using large dose per fraction treatments (aggressive hypofractionation). While SBRT has shown efficacy for treating patients with lung, liver and spine tumors, to our knowledge there have been no preclinical studies evaluating the efficacy of this treatment for prostate cancer. We investigated the dose-response characteristics of SBRT for treating human prostate cancer in a nude mouse model. MATERIALS AND METHODS: Nude mice were injected subcutaneously into the right flank with C4-2 prostate cancer cells grown in culture. A dose escalation trial was performed to assess toxicity and response. Tumor bearing animals were radiated with 3 fractions (1 per week) for a total dose of 15 Gy in 11, 22.5 Gy in 9 and 45 Gy in 10, while 8 untreated animals served as controls. The mice were weighed, and tumor volume and PSA measurements were performed at baseline and weekly until 4 weeks after treatment. RESULTS: There was no treatment related toxicity. There was a significant difference in the tumor response to higher radiation doses. In the 15 and 22.5 Gy groups mean tumor volume decreased to 58% and 90% of the original volume, respectively, but the rats experienced progressive tumor regrowth within 1 week after the completion of therapy. The 45 Gy group had a mean tumor volume and PSA decrease of greater than 90%, which was sustained 1 month after treatment in all except 2 mice. CONCLUSIONS: SBRT dose level treatments were able to significantly decrease tumor volume and PSA. However, using 15 and 22.5 Gy durable responses were not achieved except in a few mice. The 45 Gy group demonstrated sustained PSA and tumor volume decreases in most mice. These results clearly show an increasing dose-response relationship for a range of hypofractionated dose levels, as used in SBRT.

    Title Bright and Black Blood Imaging of the Carotid Bifurcation at 3.0t.
    Date May 2006
    Journal European Journal of Radiology
    Excerpt

    PURPOSE: The aim of this study was to evaluate our preliminary experience at 3.0 T with imaging of the carotid bifurcation in healthy and atherosclerotic subjects. Application at 3.0 T is motivated by the signal-to-noise gain for improving spatial resolution and reducing signal averaging requirements. MATERIALS AND METHODS: We utilized a dual phased array coil and applied 2D, 3D time of flight (TOF) and turbo spin echo (TSE) sequences with comparison of two lumen signal suppression methods for black blood (BB) TSE imaging including double inversion preparation (DIR) and spatial presaturation pulses. The signal-to-noise ratios (SNR) of healthy carotid vessel walls were compared in 2D and 3D BB TSE acquisitions. The bright and black blood multi-contrast exam was demonstrated for a complex carotid plaque. RESULTS: Contrast-to-noise (CNR) greater than 150 was achieved between the lumen and suppressed background for 3D TOF. For BB, both methods provided sufficient lumen signal suppression but slight residual flow artifacts remained at the bifurcation level. As expected 3D TSE images had higher SNR compared to 2D, but increased motion sensitivity is a significant issue for 3D at high field. For multi-contrast imaging of atherosclerotic plaque, fibrous, calcified and lipid components were resolved. The CNR ratio of fibrous (bright on PDW, T2W) and calcified (dark in T1W, T2W, PDW) plaque components was maximal in the T2W images. The 3D TOF angiogram indicating a 40% stenosis was complemented by 3D multi-planar reformat of BB images that displayed plaque extent. Detection of intimal thickening, the earliest change associated with atherosclerotic progression was observed in BB PDW images at 3.0 T. CONCLUSIONS: High SNR and CNR images have been demonstrated for the healthy and diseased carotid. Improvements in RF coils along with pulse sequence optimization, and evaluation of endogenous and exogenous contrast mechanisms will further enhance carotid imaging at 3.0T.

    Title Vulnerable Plaque Detection by 3.0 Tesla Magnetic Resonance Imaging.
    Date May 2006
    Journal Investigative Radiology
    Excerpt

    RATIONALE AND OBJECTIVES: A clinical case report is presented on a 76-year-old man who volunteered for a 3.0 T magnetic resonance (MR) carotid protocol. The subject was referred for carotid endarterectomy and histology was performed on the ex vivo specimen and compared with the in vivo images. METHODS: The 3.0 and 1.5 T (obtained for comparison) MR protocol consisted of 2-dimensional (2D) and 3-dimensional (3D) multicontrast bright and black blood imaging for detecting the lumen and vessel wall. RESULTS: The combination of multicontrast black blood transverse images and the 3D time of flight transverse images provided visualization of a narrowed internal carotid artery lumen 4 mm above of the bifurcation and the presence of a complex atherosclerotic plaque containing a large lipid pool, calcification, and intact fibrous cap. Quantitative comparisons including vessel lumen and plaque area, signal-to-noise (SNR) and contrast-to-noise (CNR) ratios were obtained for 1.5 and 3.0 T image data. Plaque composition was verified with histology. Macrophages were also detected in the shoulders of the plaque as demonstrated by CD68 staining and corresponded with a small hyperintense area in the T2W images at 3.0 T, but not observed in comparable 1.5 T images. CONCLUSIONS: High field 3.0 T multicontrast MRI of atherosclerotic plaque has been validated with histology comparison and provides improved detection of complex atherosclerotic plaque with increased SNR and CNR compared with 1.5 T. Further studies validating contrast mechanisms of plaque at 3.0 T are required, but atherosclerotic plaque imaging has clear benefit from application at the higher magnetic field strength.

    Title Study of the Therapeutic Effects of Intercessory Prayer (step) in Cardiac Bypass Patients: a Multicenter Randomized Trial of Uncertainty and Certainty of Receiving Intercessory Prayer.
    Date April 2006
    Journal American Heart Journal
    Excerpt

    BACKGROUND: Intercessory prayer is widely believed to influence recovery from illness, but claims of benefits are not supported by well-controlled clinical trials. Prior studies have not addressed whether prayer itself or knowledge/certainty that prayer is being provided may influence outcome. We evaluated whether (1) receiving intercessory prayer or (2) being certain of receiving intercessory prayer was associated with uncomplicated recovery after coronary artery bypass graft (CABG) surgery. METHODS: Patients at 6 US hospitals were randomly assigned to 1 of 3 groups: 604 received intercessory prayer after being informed that they may or may not receive prayer; 597 did not receive intercessory prayer also after being informed that they may or may not receive prayer; and 601 received intercessory prayer after being informed they would receive prayer. Intercessory prayer was provided for 14 days, starting the night before CABG. The primary outcome was presence of any complication within 30 days of CABG. Secondary outcomes were any major event and mortality. RESULTS: In the 2 groups uncertain about receiving intercessory prayer, complications occurred in 52% (315/604) of patients who received intercessory prayer versus 51% (304/597) of those who did not (relative risk 1.02, 95% CI 0.92-1.15). Complications occurred in 59% (352/601) of patients certain of receiving intercessory prayer compared with the 52% (315/604) of those uncertain of receiving intercessory prayer (relative risk 1.14, 95% CI 1.02-1.28). Major events and 30-day mortality were similar across the 3 groups. CONCLUSIONS: Intercessory prayer itself had no effect on complication-free recovery from CABG, but certainty of receiving intercessory prayer was associated with a higher incidence of complications.

    Title Hand-assisted Laparoscopic Nephrectomy for Renal Masses >9.5 Cm: Series Comparison with Open Radical Nephrectomy.
    Date December 2005
    Journal Urologic Oncology
    Excerpt

    OBJECTIVE: To assess the feasibility of hand-assisted laparoscopic nephrectomy (HALN) for large renal masses (stage T2, mean size 9.7 cm) and compare outcomes with a similar cohort undergoing open radical nephrectomy (ORN). METHODS: A nonrandomized comparison of 19 consecutive patients who underwent nephrectomy for renal masses >or=7 cm was performed. The HALN group was compared to the ORN group regarding demographic parameters and perioperative data, including blood loss, operating time, narcotic usage, hematocrit change, return to standard oral intake, length of hospital stay, and complications. Data collected prospectively and statistics used 2-tailed t-test analysis. RESULTS: Patients underwent either ORN (mean tumor size 12.3 cm) or HALN (mean tumor size 9.7cm). Tumors up to 14 cm (n = 2) and pT3b, with renal vein thrombosis (n = 2), could be safely excised with HALN. There were no differences between the HALN and ORN groups regarding any demographic parameter. Blood loss, operating time, length of stay, parenteral narcotic use, and time to tolerating regular diet were all less statistically significant in the HALN group as compared to the ORN group (P < 0.05). Tumors >15 cm necessitated ORN. CONCLUSIONS: HALN is technically feasible even for tumors with mean size >9.5 cm. There is a significant advantage to HALN over ORN regarding the intraoperative and postoperative morbidity. Tumors >or=15 cm should, in most cases, be performed with an open approach.

    Title Caffeinated Coffee Consumption and Mortality After Acute Myocardial Infarction.
    Date September 2004
    Journal American Heart Journal
    Excerpt

    BACKGROUND: Previous studies have generally suggested no effect of coffee consumption on the risk of acute myocardial infarction. The effect of coffee consumption on prognosis after acute myocardial infarction is uncertain. METHODS: In an inception cohort study, we observed 1935 patients who were hospitalized with a confirmed acute myocardial infarction between 1989 and 1994 at 45 community hospitals and tertiary care centers in the United States, as part of the Determinants of Myocardial Infarction Onset Study. Trained interviewers assessed self-reported caffeinated coffee consumption before infarction with a standardized questionnaire. We analyzed survival censored at December 31, 1995, using Cox proportional hazards regression. RESULTS: Of the 1902 patients for whom we had information on coffee intake, 315 (17%) died during a median follow-up period of 3.8 years. Coffee drinkers tended to be men, younger, and free of comorbidity, and they were more likely to be current smokers. Coffee consumption was not associated with an overall change in long-term post-infarction mortality rate. However, we did observe an unexpected and unexplained variation in the association between coffee consumption and mortality with time, with an apparent inverse association in the first 90 days after infarction. CONCLUSIONS: Self-reported coffee consumption has no overall association with post-infarction mortality. The unexpected time variation in the effect of coffee intake requires evaluation in other studies.

    Title Educational Attainment and Myocardial Infarct-related Congestive Heart Failure (the Determinants of Myocardial Infarction Onset Study).
    Date June 2004
    Journal The American Journal of Cardiology
    Excerpt

    We assessed educational attainment and complications during hospitalization in 3,882 patients with acute myocardial infarction for the Determinants of Myocardial Infarction Onset Study. Educational attainment had a graded, inverse association with prevalence of congestive heart failure (CHF) during hospitalization, with the lowest prevalence among patients who attended college (odds ratio 0.75; 95% confidence interval, 0.57 to 0.99; p for trend 0.02), with similar findings among men, women, whites, and blacks.

    Title Laparoscopic Retroperitoneal Lymph Node Dissection in the Extremely Obese Patient: Technical Insight into Access and Port Placement.
    Date January 2004
    Journal Jsls : Journal of the Society of Laparoendoscopic Surgeons / Society of Laparoendoscopic Surgeons
    Excerpt

    PURPOSE: We report on laparoscopic retroperitoneal lymph node dissection (RPLND) in a morbidly obese patient to discuss the associated technical steps for satisfactory completion of staging lymphadenectomy. METHODS: A laparoscopic RPLND was performed using a modified template on the left side. Initially, 4 ports were placed with the patient in the supine position. Three were placed 3 cm to the left of midline and one in the anterior axillary line, at the level of the umbilicus. During the operation, successful bowel retraction necessitated placement of 2 additional ports in the anterior axillary line (just above the pelvis and off the tip of the 12th rib). Using these 6 trocar sites, the dissection was completed, and 44 lymph nodes were obtained. RESULTS: Laparoscopic retroperitoneal lymph node dissection was accomplished in an extremely obese patient with acceptable morbidity by using prudent modification of standard techniques. CONCLUSION: If access and port placement limitations are overcome, the benefits of laparoscopy in the obese are clear. This report serves as a signpost that laparoscopic retroperitoneal lymph node dissection for testes cancer can also be accomplished using modification of standard techniques.

    Title Heterogeneity of 5 Alpha-reductase Gene Expression in Benign Prostatic Hyperplasia.
    Date February 2003
    Journal The Journal of Urology
    Excerpt

    PURPOSE: The search for molecular markers of benign prostatic hyperplasia in general is based on an analysis of a limited number of biopsy samples. Little is known about the homogeneity of the expression of key genes in different zones of the prostate. We studied the intraprostatic (that is within the same gland) and inter-prostatic (that is between glands) variability of 5 alpha-reductase 2 (5aR2) gene expression. MATERIALS AND METHODS: Ten tissue samples removed by open prostatectomy were the source of tissue specimens. Two frozen sections were generated from each of several random biopsies taken from each adenoma immediately after enucleation, 1 of which was used for 5aR2 gene expression analysis and 1 for morphometric analysis. Results among biopsies were compared using the 5 alpha-reductase index (ratio of 5 alpha-reductase expression to an internal standard measured as electrophoretic band intensity). Morphometric composition was determined for smooth muscle, collagen, epithelium and glandular lumens. Statistical comparisons were performed with ANOVA by pairwise multiple comparison (Dunn) and Spearman's rank correlation procedure. RESULTS: For the 71 biopsies analyzed mean 5 alpha-reductase index was 0.23 +/- 0.16 and overall tissue distribution was smooth muscle 34%, collagen 35%, epithelium 14% and glandular lumens 17%. Inter-prostate and intraprostate variability in 5 alpha-reductase index was statistically significant (p = 0.004) as was the variability in stromal-to-epithelial ratio (p = 0.012). The 5 alpha-reductase index showed strong correlation with stroma (%) and negative correlation with epithelium (%). CONCLUSIONS: Benign prostatic hyperplasia is heterogeneous in terms of tissue morphometry and expression of single important genes. This finding limits the use of single biopsy based markers to predict biological behavior, and has significant impact on the ability of distinguishing longitudinal changes in tissue composition from sampling artifacts.

    Title Comparison of Courses of Patients with Acute Myocardial Infarction with Chest Pain Appearing During Exertion Versus Those with Chest Pain Not Occurring During Exertion.
    Date October 2002
    Journal The American Journal of Cardiology
    Title Variation in the Risk of Onset of Acute Myocardial Infarction During the Menstrual Cycle.
    Date July 2002
    Journal The American Journal of Cardiology
    Title Tea Consumption and Mortality After Acute Myocardial Infarction.
    Date June 2002
    Journal Circulation
    Excerpt

    BACKGROUND: Some studies have suggested that tea consumption may be associated with lower mortality among individuals with cardiovascular disease, but the effects of tea consumption on mortality after acute myocardial infarction are unknown. METHODS AND RESULTS: As part of the Determinants of Myocardial Infarction Onset Study, we performed a prospective cohort study of 1900 patients hospitalized with a confirmed acute myocardial infarction between 1989 and 1994, with a median follow-up of 3.8 years. Trained interviewers assessed self-reported usual weekly caffeinated tea consumption during the year before infarction with a standardized questionnaire. We compared long-term mortality according to tea consumption using Cox proportional hazards regression. Of the 1900 patients, 1019 consumed no tea (nondrinkers), 615 consumed <14 cups per week (moderate tea drinkers), and 266 consumed 14 or more cups per week (heavy tea drinkers). Compared with nondrinkers, age- and sex-adjusted mortality was lower among moderate tea drinkers (hazard ratio, 0.69; 95% CI, 0.53 to 0.89) and heavy tea drinkers (hazard ratio, 0.61; 95% CI, 0.42 to 0.86). Additional adjustment for clinical and sociodemographic characteristics did not appreciably alter this association (hazard ratio, 0.72; 95% CI, 0.55 to 0.94 for moderate tea drinkers; hazard ratio, 0.56; 95% CI, 0.37 to 0.84 for heavy tea drinkers). The association of tea and mortality was similar for total and cardiovascular mortality. CONCLUSIONS: Self-reported tea consumption in the year before acute myocardial infarction is associated with lower mortality after infarction.

    Title Study of the Therapeutic Effects of Intercessory Prayer (step): Study Design and Research Methods.
    Date April 2002
    Journal American Heart Journal
    Excerpt

    BACKGROUND: The effect of intercessory prayer (IP) on outcome in cardiac cases has been evaluated previously, but results are controversial. The goals of the Study of the Therapeutic Effects of Intercessory Prayer (STEP) are to evaluate the effects of receipt of additional study IP and awareness of receipt of additional study IP on outcomes in patients undergoing coronary artery bypass graft surgery. STEP is not designed to determine whether God exists or whether God does or does not respond to IP. METHODS: STEP is a multicenter, controlled trial of 1802 patients in 6 US hospitals, randomized to 1 of 3 groups. Two groups were informed that they may or may not receive 14 consecutive days of additional IP starting the night before coronary artery bypass graft surgery; Group 1 received IP, Group 2 did not. A third group (Group 3) was informed that they would receive additional IP and did so. Three mainstream religious sites provided daily IP for patients assigned to receive IP. At each hospital, research nurses blinded to patient group assignment reviewed medical records to determine whether complications occurred, on the basis of the Society for Thoracic Surgeons definitions. A blinded nurse auditor from the Coordinating Center reviewed every study patient's data against the medical record before release of study forms. RESULTS: The STEP Data and Safety Monitoring Board reviewed patient safety and outcomes in the first 900 study patients. Patients were enrolled in STEP from January 1998 to November 2000.

    Title Height is Not Associated with Long-term Survival After Acute Myocardial Infarction.
    Date January 2002
    Journal American Heart Journal
    Excerpt

    BACKGROUND: Studies show an inverse association between height and risk of myocardial infarction. How height affects survival after acute myocardial infarction is uncertain. METHODS: In the Determinants of Myocardial Infarction Onset Study, trained interviewers performed chart reviews and face-to-face interviews with 1935 patients hospitalized with acute myocardial infarction in 45 US medical centers between 1989 and 1993. We excluded 15 patients with missing information on height. After a search of the National Death Index for patients who died before 1996, we analyzed the relationship of height and survival with Cox proportional hazards regression. RESULTS: Of the 1920 eligible patients, 317 (17%) died during a median follow-up of 3.8 years. Height was positively associated with younger age, greater educational attainment, and a lower likelihood of being sedentary among both men and women. Height was not associated with long-term survival among women in unadjusted or adjusted analyses. Among men, height was associated with survival only in unadjusted analyses; adjustment for age eliminated this association. We found no relationship between height and survival in any individual age group among men or women. CONCLUSIONS: Although stature may be associated with the risk of acute myocardial infarction, it is not associated with long-term survival after such an event.

    Title Evaluation of Sex-related Differences in Survival After Hospitalization for Acute Myocardial Infarction.
    Date December 2001
    Journal The American Journal of Cardiology
    Title Impact of Diabetes on Long-term Survival After Acute Myocardial Infarction: Comparability of Risk with Prior Myocardial Infarction.
    Date September 2001
    Journal Diabetes Care
    Excerpt

    OBJECTIVE: To determine the effect of diabetes on long-term survival after acute myocardial infarction and to compare its effect with that of a previous myocardial infarction. RESEARCH DESIGN AND METHODS: In a prospective cohort study, we followed 1,935 patients hospitalized with a confirmed acute myocardial infarction at 45 U.S. medical centers between 1989 and 1993, as part of the Determinants of Myocardial Infarction Onset Study. Trained interviewers performed chart reviews and face-to-face interviews with all patients. We analyzed survival using Cox proportional hazards regression to control for potentially confounding factors. RESULTS: Of the 1,935 patients, 320 (17%) died during a mean follow-up of 3.7 years. A total of 399 patients (21%) had previously diagnosed diabetes. Diabetes was associated with markedly higher total mortality in unadjusted (hazard ratio [HR] 2.4; 95% CI 1.9-3.0) and adjusted (1.7; 1.3-2.1) analyses. The magnitude of the effect of diabetes was identical to that of a previous myocardial infarction. The effect of diabetes was not significantly modified by age, smoking, household income, use of thrombolytic therapy, type of hypoglycemic treatment, or duration of diabetes, but the risk associated with diabetes was higher among women than men (adjusted HRs 2.7 vs. 1.3, P = 0.01). CONCLUSIONS: Diabetes is associated with markedly increased mortality after acute myocardial infarction, particularly in women. The increase in risk is of the same magnitude as a previous myocardial infarction and provides further support for aggressive treatment of coronary risk factors among diabetic patients.

    Title Triggering Myocardial Infarction by Marijuana.
    Date July 2001
    Journal Circulation
    Excerpt

    BACKGROUND: Marijuana use in the age group prone to coronary artery disease is higher than it was in the past. Smoking marijuana is known to have hemodynamic consequences, including a dose-dependent increase in heart rate, supine hypertension, and postural hypotension; however, whether it can trigger the onset of myocardial infarction is unknown. METHODS AND RESULTS: In the Determinants of Myocardial Infarction Onset Study, we interviewed 3882 patients (1258 women) with acute myocardial infarction an average of 4 days after infarction onset. We used the case-crossover study design to compare the reported use of marijuana in the hour preceding symptoms of myocardial infarction onset to its expected frequency using self-matched control data. Of the 3882 patients, 124 (3.2%) reported smoking marijuana in the prior year, 37 within 24 hours and 9 within 1 hour of myocardial infarction symptoms. Compared with nonusers, marijuana users were more likely to be men (94% versus 67%, P<0.001), current cigarette smokers (68% versus 32%, P<0.001), and obese (43% versus 32%, P=0.008). They were less likely to have a history of angina (12% versus 25%, P<0.001) or hypertension (30% versus 44%, P=0.002). The risk of myocardial infarction onset was elevated 4.8 times over baseline (95% confidence interval, 2.4 to 9.5) in the 60 minutes after marijuana use. The elevated risk rapidly decreased thereafter. CONCLUSIONS: Smoking marijuana is a rare trigger of acute myocardial infarction. Understanding the mechanism through which marijuana causes infarction may provide insight into the triggering of myocardial infarction by this and other, more common stressors.

    Title Prior Alcohol Consumption and Mortality Following Acute Myocardial Infarction.
    Date May 2001
    Journal Jama : the Journal of the American Medical Association
    Excerpt

    CONTEXT: Studies have found that individuals who consume 1 alcoholic drink every 1 to 2 days have a lower risk of a first acute myocardial infarction (AMI) than abstainers or heavy drinkers, but the effect of prior drinking on mortality after AMI is uncertain. OBJECTIVE: To determine the effect of prior alcohol consumption on long-term mortality among early survivors of AMI. DESIGN AND SETTING: Prospective inception cohort study conducted at 45 US community and tertiary care hospitals between August 1989 and September 1994, with a median follow-up of 3.8 years. PATIENTS: A total of 1913 adults hospitalized with AMI between 1989 and 1994. MAIN OUTCOME MEASURE: All-cause mortality, compared by self-reported average weekly consumption of beer, wine, and liquor during the year prior to AMI. RESULTS: Of the 1913 patients, 896 (47%) abstained from alcohol, 696 (36%) consumed less than 7 alcoholic drinks/wk, and 321 (17%) consumed 7 or more alcoholic drinks/wk. Compared with abstainers, patients who consumed less than 7 drinks/wk had a lower all-cause mortality rate (3.4 vs 6.3 deaths per 100 person-years; hazard ratio [HR], 0.55; 95% confidence interval [CI], 0.43-0.71) as did those who consumed 7 or more drinks/wk (2.4 vs 6.3 deaths per 100 person-years; HR, 0.38; 95% CI, 0.25-0.55; P<.001 for trend). After adjusting for propensity to drink and other potential confounders, increasing alcohol consumption remained predictive of lower mortality for less than 7 drinks/wk, with an adjusted HR of 0.79 (95% CI, 0.60-1.03), and for 7 or more drinks/wk, with an adjusted HR of 0.68 (95% CI, 0.45-1.05; P =.01 for trend). The association was similar for total and cardiovascular mortality, among both men and women, and among different types of alcoholic beverages. CONCLUSION: Self-reported moderate alcohol consumption in the year prior to AMI is associated with reduced mortality following infarction.

    Title Chromosome 4 Deletions Are Frequent in Invasive Cervical Cancer and Differ Between Histologic Variants.
    Date October 2000
    Journal Gynecologic Oncology
    Excerpt

    OBJECTIVE: Patterns of discontinuous deletion of chromosome 4 have been described in histologic variants of lung carcinomas and may represent different "hotspot" targets for gene-environment interactions. Since similar environmental risks exist for cervical cancer, we investigated patterns of discontinuous deletion in two major histologic variants. METHODS: Thirteen archival cases of squamous cell cancer (SCCA) and 11 cases of adenocarcinoma (AC) were precisely microdissected. Matched normal and tumor DNA were used for polymerase chain reaction (PCR) based loss of heterozygosity (LOH) analyses using 19 polymorphic markers spanning chromosome 4. Human papillomavirus (HPV) detection was determined by PCR using general and type-specific primers (HPV 16, 18). Differences in LOH between histologic tumor types and chromosomal regions were determined using Fisher's exact test. RESULTS: Loss at any chromosome 4 locus occurred in 92% of all tumors studied, with the majority of deletions occurring on the long arm of the chromosome. Four discrete minimal regions of discontinuous deletion (R) were identified. For these regions, LOH frequencies were 76% (R1, 4q34-q35), 48% (R2, 4q25-q26), 36% (R3, 4p15.1-p15.3), and 26% (R4, 4p16). Loss in SCCA predominated at 4q (4q34-q35; 83%) and in AC at 4p (4p15.3; 50%). Overall LOH on the p arm was significant in AC (82%) compared to SCCA (31%) (P = 0.02). HPV detection was similar in SCCA (85%) and AC (73%), and HPV 16/18 subtypes were similarly represented in both histologies. CONCLUSIONS: Chromosome 4 deletions are frequent in cervical carcinomas. Different patterns of deletion between SCCA and AC may represent gene regions targeted by different gene-environment interactions in these tumor subtypes.

    Title Increased Risk of Congestive Heart Failure Among Infarctions with Nighttime Onset.
    Date September 2000
    Journal American Heart Journal
    Excerpt

    BACKGROUND: The onset of acute myocardial infarction varies by time of day, with a peak in the morning and a trough at night. Whether infarct-related complications differ by the timing of the infarction is unknown.Methods And Results: In the Determinants of Myocardial Infarction Onset Study, we performed chart reviews and face-to-face interviews with 3625 patients with acute myocardial infarction. We assessed the time of onset of symptoms, the presence of ventricular tachycardia or congestive heart failure, and peak creatine kinase levels (in 1043 patients). We found significant circadian variation in the risk of congestive heart failure (P =.001). The risk dropped from 17% for infarctions that began between 6 PM and midnight to 10% for infarctions that began between 6 AM and noon. Adjustment for differences in the time from symptom onset to presentation for care and use of thrombolytic agents did not change the results. We found no circadian variation in the risk of ventricular tachycardia or in peak creatine kinase levels. CONCLUSIONS: The risk of congestive heart failure is highest among infarctions that begin at night. Further research may clarify whether this reflects differences in the pathophysiologic characteristics of infarction or the quality of medical care provided for daytime and nighttime infarctions.

    Title Lack of Effect of Recent Alcohol Consumption on the Course of Acute Myocardial Infarction.
    Date November 1999
    Journal American Heart Journal
    Excerpt

    BACKGROUND AND OBJECTIVE: Alcohol has marked effects on hemodynamic and hemostatic variables that might alter the presentation of acute myocardial infarction that follows its use. We sought to determine whether recent alcohol consumption alters the course or complications of acute myocardial infarction. METHODS: In the Determinants of Myocardial Infarction Onset Study, we performed chart reviews and face-to-face interviews with 2161 patients who did not receive thrombolytic therapy. We assessed alcohol use before infarction, peak creatine kinase levels (1043 patients), electrocardiographic interpretations (1408 patients), and the presence of ventricular arrhythmias or congestive heart failure (all patients). RESULTS: Among the 2161 patients, 399 (18.5%) drank alcohol within 24 hours before myocardial infarction. We found no significant difference in mean peak creatine kinase level between those who had recently used alcohol and those who had not in an adjusted comparison (-6.1% difference; 95% confidence interval [CI] -20.3%-10.7%; P =.46). We also found no differences in adjusted risk for Q-wave infarction, congestive heart failure, or ventricular arrhythmias (odds ratios 1.03 [95% CI, 0.73-1.45; P =.88], 1.01 [95% CI, 0.67-1.54; P =.95], and 1.04 [95% CI, 0.66-1.65; P =.86]). Categorization of the duration since last alcohol use into 6-hour intervals revealed no trends between time since last use of alcohol and any of these outcomes. CONCLUSIONS: Recent alcohol use is not associated with changes in infarct size or risk for Q-wave infarction, congestive heart failure, or ventricular arrhythmia among this population.

    Title Triggering of Myocardial Infarction by Cocaine.
    Date July 1999
    Journal Circulation
    Excerpt

    BACKGROUND: Cocaine has been implicated as a trigger of acute myocardial infarction in patients with and those without underlying coronary atherosclerosis. However, the magnitude of the increase in risk of acute myocardial infarction immediately after cocaine use remains unknown. METHODS AND RESULTS: In the Determinants of Myocardial Infarction Onset Study, we interviewed 3946 patients (1282 women) with acute myocardial infarction an average of 4 days after infarction onset. Data were collected on the use of cocaine and other potential triggers of myocardial infarction. We compared the reported use of cocaine in the hour preceding the onset of myocardial infarction symptoms with its expected frequency by using self-matched control data based on the case-crossover study design. Of the 3946 patients interviewed, 38 (1%) reported cocaine use in the prior year and 9 reported use within the 60 minutes preceding the onset of infarction symptoms. Compared with nonusers, cocaine users were more likely to be male (87% vs 67%, P=0.01), current cigarette smokers (84% vs 32%, P<0.001), younger (44+/-8 vs 61+/-13 years, P<0.001), and minority group members (63% vs 11%, P<0.001). The risk of myocardial infarction onset was elevated 23.7 times over baseline (95% CI 8.5 to 66.3) in the 60 minutes after cocaine use. The elevated risk rapidly decreased thereafter. CONCLUSIONS: Cocaine use is associated with a large abrupt and transient increase in the risk of acute myocardial infarction in patients who are otherwise at relatively low risk. This finding suggests that studying the pathophysiological changes produced by cocaine may provide insights into the mechanisms by which myocardial infarction is triggered by other stressors.

    Title Recent Aspirin Use is Associated with Smaller Myocardial Infarct Size and Lower Likelihood of Q-wave Infarction.
    Date July 1999
    Journal American Heart Journal
    Excerpt

    BACKGROUND: Controversy exists about the effect of recent aspirin use on infarct size and the likelihood of Q-wave infarction in patients who sustain myocardial infarction. METHODS: We performed face-to-face interviews and chart reviews on 3665 patients with acute myocardial infarction for the Determinants of Myocardial Infarction Onset Study. For the 2206 patients who did not receive thrombolytic therapy, we assessed aspirin use, peak creatine kinase levels (in 1043 patients), and electrocardiographic interpretations (in 1447 patients). RESULTS: Of the initial 1043 patients, 317 (30. 3%) subjects reported aspirin use in the 4 days before their infarction. The mean +/- SD peak creatine kinase level for aspirin users was 701 +/- 570 IU/mL versus 851 +/- 727 IU/mL for nonusers, an 18% difference (95% confidence interval [CI], 8% to 26%; P <.001). After adjustment for confounding factors, the difference was 12% (95% CI, 2% to 21%; P =.03). Similarly, 38.9% of the aspirin users and 48.7% of the nonusers sustained a Q-wave infarction, an odds ratio of 0.67 (95% CI, 0.54 to 0.83, P <.001). The adjusted odds ratio was 0.77 (95% CI, 0.61 to 0.97, P =.03). CONCLUSIONS: Recent aspirin use was associated with smaller infarct size and fewer Q-wave infarctions among this population of early survivors of acute myocardial infarction who did not receive thrombolytic therapy.

    Title Endometrial Cancer in Polyps Associated with Tamoxifen Use.
    Date March 1999
    Journal American Journal of Obstetrics and Gynecology
    Excerpt

    We report 5 cases of carcinoma arising within tamoxifen-associated endometrial polyps. In 4 of 5 cases there were no other changes within the endometrium. Given these findings, the sonohysterographic differentiation between a polypoid structure and thickened endometrium does not eliminate the need for histologic sampling of the uterine cavity.

    Title Squamous Metaplasia of the Endometrium Associated with Hpv 6 and 11.
    Date August 1997
    Journal Gynecologic Oncology
    Excerpt

    Although uncommon in the endometrium, squamous metaplasia, dysplasia, and squamous carcinoma have been observed. Associated human papillomavirus (HPV) infection is also unusual, due at least in part to the fact that HPV requires specific characteristics of the target epithelium for infectivity. We report a case of extensive squamous metaplasia with focal low-grade squamous intraepithelial neoplasia of the endometrium coexistent with low-grade cervical intraepithelial neoplasia and an invasive squamous carcinoma of the vagina. In situ hybridization studies revealed HPV types 6 and 11 in both the cervical and endometrial lesions. This is the first report to date to demonstrate squamous epithelial metaplasia and dysplasia of the endometrium, associated with HPV DNA of viruses typically of low oncogenic potential.

    Title Educational Attainment, Anger, and the Risk of Triggering Myocardial Infarction Onset. The Determinants of Myocardial Infarction Onset Study Investigators.
    Date April 1997
    Journal Archives of Internal Medicine
    Excerpt

    BACKGROUND: While it has recently been shown that anger may trigger the onset of acute myocardial infarction, there has been no study of the role of socioeconomic factors in such triggering. Socioeconomic factors, such as educational attainment, may modulate the risk of triggering because of their influence on individual reactivity to external stressors and on the prevalence of traditional cardiac risk factors. OBJECTIVE: To evaluate the influence of educational attainment on the relative risk of myocardial infarction onset following episodes of anger. METHODS: We interviewed 1623 patients (501 women) an average of 4 days following a myocardial infarction. Data were collected on standard demographic variables as well as risk factors for coronary artery disease. Educational attainment was categorized into 3 levels: less than high school, completed high school, and at least some college. Anger was assessed by the Onset Anger Scale, a single-item, 7-level, self-report scale. Occurrence of anger in the 2 hours preceding the onset of myocardial infarction was compared with its expected frequency using self-matched control data based on the case-crossover study design. RESULTS: The risk of having a myocardial infarction triggered by isolated episodes of anger declined consistently and significantly with increasing levels of educational attainment (P = .03). The relative risk was twice as high among those with less than high school education (relative risk, 3.3; 95% confidence interval, 2.0-5.4) compared with patients with at least some college education (relative risk, 1.6; 95% confidence interval, 0.9-2.9). CONCLUSIONS: These findings indicate that socioeconomic factors are potent modulators of the risk of triggering acute cardiovascular disease onset. A better understanding of the physiological mechanisms underlying this association may lead to novel approaches to prevent acute cardiovascular events.

    Title Triggering Myocardial Infarction by Sexual Activity. Low Absolute Risk and Prevention by Regular Physical Exertion. Determinants of Myocardial Infarction Onset Study Investigators.
    Date June 1996
    Journal Jama : the Journal of the American Medical Association
    Excerpt

    OBJECTIVE--To determine the relative risks of nonfatal myocardial infarction (MI) triggered by sexual activity among the general population and in patients with prior coronary heart disease. DESIGN--Relative risks and effect modification were calculated by the case-crossover method, a new epidemiologic technique designed to quantify the transient change in risk following exposure to a potential disease trigger. SETTING/PARTICIPANTS--A total of 1774 patients with MI were interviewed in 45 hospitals throughout the United States. Data were gathered on potential triggers of MI occurring immediately prior to the event and during the previous year. Results are presented for the 858 patients who were sexually active in the year prior to the MI, with attention to the 273 patients who had coronary artery disease prior to their index MI, and the effect of regular exertion on risk. MAIN OUTCOME MEASURE--The relative risk of nonfatal MI following sexual activity. RESULTS--Of the 858 patients, 79(9%) reported sexual activity in the 24 hours preceding MI, and 27(3%) reported sexual activity in the 2 hours preceding onset of symptoms of MI. The relative risk of MI occurring in the 2 hours after sexual activity was 2.5(95% confidence interval [CI], 1.7-3.7). The relative risk of triggering onset of MI among patients with a history of prior angina (2.1 [95% CI, 0.8-5.8]) or prior MI (2.9 [95% CI, 1.3-6.5]) was not greater than that observed in those without prior cardiac disease. Sexual activity was a likely contributor to the onset of MI in only 0.9% of cases and regular exertion was associated with decreasing risk. CONCLUSIONS--Sexual activity can trigger the onset of MI. However, the relative risk is low, and since the absolute hourly risk of MI is extremely low, the absolute risk increase caused by sexual activity also is extremely low (1 chance in a million for a healthy individual). Moreover, the relative risk is not increased in patients with a prior history of cardiac disease and regular exercise appears to prevent triggering. These findings should be useful for counseling patients and decreasing the fear of sexual activity that often prevents complete rehabilitation from cardiovascular disease.

    Title Triggering of Acute Myocardial Infarction Onset by Episodes of Anger. Determinants of Myocardial Infarction Onset Study Investigators.
    Date October 1995
    Journal Circulation
    Excerpt

    BACKGROUND: Many anecdotes and several uncontrolled case series have suggested that emotionally stressful events, and more specifically, anger, immediately precede and appear to trigger the onset of acute myocardial infarction. However, controlled studies to determine the relative risk of myocardial infarction after episodes of anger have not been reported. METHODS AND RESULTS: We interviewed 1623 patients (501 women) an average of 4 days after myocardial infarction. The interview identified the time, place, and quality of myocardial infarction pain and other symptoms, the estimated usual frequency of anger during the previous year, and the intensity and timing of anger and other potentially triggering factors during the 26 hours before the onset of myocardial infarction. Anger was assessed by the onset anger scale, a single-item, seven-level, self-report scale, and the state anger subscale of the State-Trait Personality Inventory. Occurrence of anger in the 2 hours preceding the onset of myocardial infarction was compared with its expected frequency using two types of self-matched control data based on the case-crossover study design. The onset anger scale identified 39 patients with episodes of anger in the 2 hours before the onset of myocardial infarction. The relative risk of myocardial infarction in the 2 hours after an episode of anger was 2.3 (95% confidence interval, 1.7 to 3.2). The state anger subscale corroborated these findings with a relative risk of 1.9 (95% confidence interval, 1.3 to 2.7). Regular users of aspirin had a significantly lower relative risk (1.4; 95% confidence interval, 0.8 to 2.6) than nonusers (2.9; 95% confidence interval, 2.0 to 4.1) (P < .05). CONCLUSIONS: Episodes of anger are capable of triggering the onset of acute myocardial infarction, but aspirin may reduce this risk. A better understanding of the manner in which external events trigger the onset of acute cardiovascular events may lead to innovative preventive strategies aimed at severing the link between these external stressors and their pathological consequences.

    Title Erythropoietin Levels During Theophylline Treatment in Premature Infants.
    Date February 1994
    Journal The Journal of Pediatrics
    Excerpt

    Mean erythropoietin levels were somewhat higher in premature infants receiving theophylline than in untreated infants with a comparable degree of anemia. These results differ from those in adults and may reflect the oxygenation of the theophylline-treated patients or the developmental regulation of erythropoietin production in response to adenosine receptor antagonists.

    Title Triggering of Acute Myocardial Infarction by Heavy Physical Exertion. Protection Against Triggering by Regular Exertion. Determinants of Myocardial Infarction Onset Study Investigators.
    Date December 1993
    Journal The New England Journal of Medicine
    Excerpt

    BACKGROUND. Despite anecdotal evidence suggesting that heavy physical exertion can trigger the onset of acute myocardial infarction, there have been no controlled studies of the risk of myocardial infarction during and after heavy exertion, the length of time between heavy exertion and the onset of symptoms (induction time), and whether the risk can be modified by regular physical exertion. To address these questions, we collected data from patients with confirmed myocardial infarction on their activities one hour before the onset of myocardial infarction and during control periods. METHODS. Interviews with 1228 patients conducted an average of four days after myocardial infarction provided data on their usual annual frequency of physical activity and the time, type, and intensity of physical exertion in the 26 hours before the onset of myocardial infarction. We compared the observed frequency of heavy exertion (6 or more metabolic equivalents) with the expected values using two types of self-matched analyses based on a new case-crossover study design. The low frequency of heavy exertion during the control periods was validated by data from a population-based control group of 218 subjects. RESULTS. Of the patients, 4.4 percent reported heavy exertion within one hour before the onset of myocardial infarction. The estimated relative risk of myocardial infarction in the hour after heavy physical exertion, as compared with less strenuous physical exertion or none, was 5.9 (95 percent confidence interval, 4.6 to 7.7), Among people who usually exercised less than one, one to two, three to four, or five or more times per week, the respective relative risks were 107 (95 percent confidence interval, 67 to 171), 19.4 (9.9 to 38.1), 8.6 (3.6 to 20.5), and 2.4 (1.5 to 3.7). Thus, increasing levels of habitual physical activity were associated with progressively lower relative risks. The induction time from heavy exertion to the onset of myocardial infarction was less than one hour, and symptoms usually began during the activity. CONCLUSIONS. Heavy physical exertion can trigger the onset of acute myocardial infarction, particularly in people who are habitually sedentary. Improved understanding of the mechanisms by which heavy physical exertion triggers the onset of myocardial infarction and the manner in which regular exertion protects against it would facilitate the design of new preventive approaches.

    Title A Human Adult Wilms' Tumor. Histologic, Ultrastructural, and Cytogenetic Analysis.
    Date October 1989
    Journal Cancer Genetics and Cytogenetics
    Excerpt

    The cytogenetic, histologic, and electron microscopic studies of an adult patient with Wilms' tumor are presented. Wilms' tumor (nephroblastoma) is a common renal tumor of childhood but is extremely rare in people over 15 years old. The histologic analysis of the patient's tumor, including both light and electron microscopic analysis, indicated that this tumor satisfies the histologic criteria for an adult Wilms' tumor, namely, blastemic cells that are immature renal parenchymal cells, embryonic tubular structures, and a scanty stromal component consisting of loosely arranged spindle cells. The tumor showed several ultrastructural features characteristic of adult Wilms' tumor, namely, markedly elongated mitochondria, autophagic vacuoles, and intracytoplasmic filaments. Karyotypic analysis was performed on the patient's peripheral leukocytes and tumor cells. The leukocytes showed no significant increase in gaps and breaks, and the patient appears to have a normal male karyotype. Some interesting chromosomal anomalies were observed in the cultured tumor cells: at least one chromosome 13, both chromosomes 22, and the X chromosome are missing, three markers are present, and there is a possible deletion of 12p.

    Title Production of Erythropoietin by an Established Human Renal Carcinoma Cell Line: in Vitro and in Vivo Studies.
    Date March 1989
    Journal Advances in Experimental Medicine and Biology
    Title Erythropoietin-induced Polycythemia in Athymic Mice Following Transplantation of a Human Renal Carcinoma Cell Line.
    Date June 1988
    Journal Cancer Research
    Excerpt

    An established cloned human renal carcinoma line RC-1, which has been continuously maintained in culture for several years and which produces erythropoietin, was injected s.c. into BALB/c athymic mice and produced tumors. Tumorigenicity was directly correlated with the number of RC-1 cells inoculated. Tumor cell histology resembled the original patient-derived tumor. Tumor-bearing mice developed hepatosplenomegaly and significant reticulocytosis with elevated hemoglobin and hematocrit values that were proportional to tumor mass. In addition, red cell mass and blood volume of nude mice increased over 100% as compared to control mice or to animals bearing nonrelevant neoplasms. Large amounts of immunoreactive erythropoietin could be extracted from the nude mouse RC-1 tumors. These results indicate that the RC-1 cell line is tumorigenic and produces biologically active erythropoietin in vivo in athymic mouse hosts, thus providing a reproducible model to study ectopic erythropoietin production and its regulation in vivo.

    Title The Heterogeneity of Circulating Human Serum Erythropoietin.
    Date April 1988
    Journal Endocrinology
    Excerpt

    The presence of more than one form of immunoreactive erythropoietin was suggested by discrepancies between the levels of immunologically detectable and biologically active erythropoietin in the sera of normal individuals and patients with end-stage renal disease. In both groups, the level of immunologically detectable hormone was significantly higher than that of bioactive hormone. Sera from end-stage renal disease patients and normal subjects were fractionated on a gel permeation column, and the immunoreactive erythropoietin in the fractions was measured by RIA. Three classes of immunoreactive erythropoietin were found in the sera: one eluting before the [125I]erythropoietin marker, one coinciding with the [125I]erythropoietin marker, and a third eluting after the labeled tracer in the region of the cytochrome c marker. The high and low mol wt components were more immunoreactive than the human urinary erythropoietin standard in the RIA. Biological activity, as determined in the in vitro rat bone marrow assay, was found only in the material eluting with the erythropoietin tracer. These studies show that immunoreactive erythropoietin in the serum consists of three components with different immunoreactivities: high and low mol wt components and a component with a mol wt similar to that of the native hormone.

    Title Stimulation by Camp of Erythropoietin Secretion by an Established Human Renal Carcinoma Cell Line.
    Date May 1987
    Journal Blood
    Excerpt

    We used our recently reported stable, transformed human renal carcinoma cell line as a model system to study the role of 3',5'-adenosine monophosphate (cAMP) in erythropoietin secretion. The erythropoietin produced by these cells is both biologically active and immunologically cross-reactive with purified native human hormone in our radioimmunoassay. Erythropoietin release by these renal carcinoma cells appears to be stimulated by cAMP as well as by the phosphodiesterase inhibitor 3-isobutyl-1-methyl-xanthine (MIX). The response to cAMP involves a rapid and enhanced release of hormone, which occurred within 30 minutes of exposure of the cells to the effector and continued for at least 4 hours. Intracellular erythropoietin was higher in the control cultures than in the cells treated with cAMP, suggesting that cAMP stimulates the release of a storage pool of hormone. The ability of cAMP and MIX to elicit the release of erythropoietin suggests that a cAMP-mediated mechanism is involved in the release of this hormone.

    Title Sickle Cell Anemia Patients Have Low Erythropoietin Levels for Their Degree of Anemia.
    Date February 1986
    Journal Blood
    Excerpt

    We have studied serum immunoreactive erythropoietin (SIE) levels in 28 patients with sickle cell anemia (SCA) without renal insufficiency and in 17 patients with nonhemoglobinopathy anemias of comparable severity using a sensitive radioimmunoassay procedure. An exponential relationship between SIE level and degree of anemia was noted in all patients. However, in nonhemoglobinopathy anemia, a sharp rise in the SIE level occurred as hemoglobin (Hb) levels fell below about 12 g/dL, whereas in sickle cell patients the increase was not marked until hemoglobin fell to about 9 g/dL. The response was more blunted in older SCA patients than in younger ones. A linear regression model relating SIE level to Hb level, presence/absence of SCA, and age explained 63% of the variation in SIE. We conclude that the serum erythropoietin levels in SCA increased at a lower hemoglobin concentration and are of a lower magnitude than that of the other anemias.

    Title Continuous Production of Erythropoietin by an Established Human Renal Carcinoma Cell Line: Development of the Cell Line.
    Date February 1986
    Journal Proceedings of the National Academy of Sciences of the United States of America
    Excerpt

    Establishment of a stable, transformed human renal carcinoma cell line that produces erythropoietin in vitro and has maintained this function continuously since 1981 and for greater than 150 passages in monolayer culture was accomplished by transplantation of human renal clear cell carcinoma tissue from a patient with erythrocytosis into an immunosuppressed athymic mouse. In addition to its immunocrossreactivity with native human urinary erythropoietin, the tumor erythropoietin demonstrates biological activity in the in vitro mouse erythroid colony-forming unit assay and in tumor-bearing nude mice. The cloned renal carcinoma cell line has an abnormal human karyotype and has ultrastructural features characteristic of human renal clear cell carcinoma. This cell line provides a reproducible model system for the production of an erythropoietin-like material and for the study of its synthesis and secretion.

    Title The Chemistry and Physiology of Erythropoietin.
    Date May 1985
    Journal Vitamins and Hormones
    Title Radioimmunoassay of Erythropoietin.
    Date October 1981
    Journal British Journal of Haematology
    Title A Radioimmunoassay for Erythropoietin.
    Date November 1979
    Journal Blood
    Excerpt

    We describe the development of a radioimmunoassay (RIA) for erythropoietin. Antisera were raised in rabbits with an impure human urinary erythropoietin preparation used as immunogen, but with pure human erytropoietin serving as the labeled antigen in the RIA and as a primary standard. The immunoreactivity of erythropoietin is not altered significantly by the mode of labeling with radioiodine, even though the biologic activity is lost. With this method, it is possible to detect 2--3 mU of erythropoietin in a volume of 0.1--0.3 ml. Therefore, the method can be used for detection of normal and subnormal serum titers as well as elevated titers. RIA for erythropoietin does not distinguish between the native (active in vivo) and the asialo form (inactive in vivo) and cannot yet be used for routine monitoring of crude fractions during purification.

    Title Extraction of Erythropoietin from Normal Kidneys.
    Date May 1979
    Journal Endocrinology
    Excerpt

    Significant amounts of active erythropoietin were extracted from the kidneys of normal rats, cattle, dogs, and rabbits by homogenization of the organs in 0.1 M phosphate buffer. The mean erythropoietin activities of the extracts, as determined by the starved-rat assay, were 0.26 U/g beef kidney, 0.41 U/g dog kidney, and 0.11 U/g rat kidney. The dog kidney extracts had a mean activity of 0.35 U/g, as measured by stimulation of hemoglobin synthesis in cultured bone marrow cells (in vitro assay) and produced a dose-dependent stimulation of 59Fe incorporation into circulating red cells when assayed in polycythemic mice. Extracts of rabbit kidney cortices had a mean activity of 2.12 U/g, as measured by stimulation of hemoglobin synthesis in cultured bone marrow cells. When the dog kidney homogenate was fractionated on DEAE-cellulose, all of the erythropoietin activity was adsorbed to the exchanger in the presence of 0.01 M acetate buffer, pH 4.5, and was completely eluted by 0.1 M Na2HPO4-0.5 M NaCl, pH 8. An antibody made against human urinary erythropoietin completely inactivated the erythropoietic factor in the dog kidney extract. Serum from a donor dog had no erythropoietin activity when assayed in the starved rat, suggesting that the factor in the extracts is intracellular erythropoietin rather than that contained in plasma trapped in the renal vasculature. The complete inactivation of the erythropoietic factor in these kidney homogenates by antierythropoietin and its behavior on DEAE-cellulose indicate that this factor is structurally similar to native plasma erythropoietin. The extracts are completely active without being incubated in the presence of serum.

    Title Erythropoietin Production by Human Renal Carcinoma Cells in Culture.
    Date October 1976
    Journal Endocrinology
    Excerpt

    Cells from human renal tumors were grown in monolayer cultures, and the media obtained at each medium change were assayed for erythropoietin activity. The medium from carcinoma I (a granular cell tumor) contained a high level of activity initially. The concentration of erythropoietin activity decreased with time in culture, but was significantly higher than that in controls after four months in vitro. There was , in addition, evidence of an inhibitory material present in the culture media. The activity formed by the tumor cells could be neutralized by an antibody to human urinary erythropoietin. The difference between activity measured in marrow cell cultures and that found by in vitro assay, and the chromatographic properties of the active preparation, suggest that the tumor-derived activity may be largely asialoerthropoietin. Two other renal carcinomas, of a different cellular type, produced significant erythropoietic activity.

    Title Production of Erythrogenin by Organ Cultures of Rat Kidney.
    Date September 1972
    Journal Blood
    Title Cold-reacting Antibodies: Differences in the Reaction of Anti-i Antibodies with Adult and Cord Red Blood Cells.
    Date August 1970
    Journal Blood

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