37 results on '"Cohen CJ"'
Search Results
2. Uterine carcinosarcomas and grade 3 endometrioid cancers: evidence for distinct tumor behavior.
- Author
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Bansal N, Herzog TJ, Seshan VE, Schiff PB, Burke WM, Cohen CJ, and Wright JD
- Published
- 2008
- Full Text
- View/download PDF
3. Immune Monitoring of Patients Treated With a Whole-Cell Melanoma Vaccine Engineered to Express 4-1BBL.
- Author
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Engelstein R, Merims S, Eisenberg G, Cohen J, Frank S, Hamburger T, Frankenburg S, Ron I, Isacson R, Grenader T, Steinberg H, Cohen CJ, Peretz T, and Lotem M
- Subjects
- 4-1BB Ligand genetics, Adult, Aged, Cell Line, Cytotoxicity, Immunologic, Female, Genetic Engineering, HLA-A2 Antigen genetics, Humans, Interferon-gamma metabolism, Lymphocyte Activation, Lysosomal-Associated Membrane Protein 1 metabolism, Male, Melanoma mortality, Middle Aged, Monitoring, Immunologic, Monitoring, Physiologic, Neoplasm Staging, Survival Analysis, Young Adult, 4-1BB Ligand metabolism, CD8-Positive T-Lymphocytes immunology, Cancer Vaccines immunology, HLA-A2 Antigen metabolism, Melanoma therapy
- Abstract
CD8 lymphocytes are mandatory mediators of tumor regression. To enhance their specific antitumor activity, we aimed to improve a melanoma cell-based vaccine by transfecting it with 4-1BB ligand, a costimulatory and immune modulatory molecule. Thirty-four American Joint Committee on Cancer (AJCC) stage IIB-IV patients were vaccinated with a melanoma antigen-rich cell line engineered to express HLA-A2 and 4-1BBL (M20/A2/BBL). Twelve serially recruited patients were monitored for interferon γ expression and CD107a mobilization before and after vaccination. Thirty-three patients remained alive, with an estimated mean overall survival of 26.2 months. No grade 3-4 adverse events were encountered. Immune monitoring detected an increase in circulating antimelanoma CD8 T cells in 9 of 12 patients, which were significantly stimulated by the parental melanoma, reflecting a relevant antitumor response. The results from this study show that the costimulatory 4-1BB ligand fortifies an antigen-rich melanoma cell line with enhanced antigen-specific stimulation of CD8 T cells. The use of a costimulatory molecule as part of a vaccine confers a selective increase of T-cell subsets with antimelanoma reactivity, which in some cases were characterized for their epitope specificity.
- Published
- 2016
- Full Text
- View/download PDF
4. Rilpivirine vs. efavirenz-based single-tablet regimens in treatment-naive adults: week 96 efficacy and safety from a randomized phase 3b study.
- Author
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van Lunzen J, Antinori A, Cohen CJ, Arribas JR, Wohl DA, Rieger A, Rachlis A, Bloch M, Segal-Maurer S, Garner W, Porter D, Bosse M, Piontkowsky D, Chuck SK, and De-Oertel S
- Subjects
- Adult, Alkynes, Antiretroviral Therapy, Highly Active adverse effects, Antiretroviral Therapy, Highly Active methods, CD4 Lymphocyte Count, Cyclopropanes, Drug Resistance, Viral, Drug-Related Side Effects and Adverse Reactions epidemiology, Drug-Related Side Effects and Adverse Reactions pathology, Female, HIV-1 isolation & purification, Humans, Male, Middle Aged, Quality of Life psychology, RNA, Viral blood, Tablets administration & dosage, Tablets adverse effects, Treatment Outcome, Viral Load, Anti-HIV Agents administration & dosage, Anti-HIV Agents adverse effects, Benzoxazines administration & dosage, Benzoxazines adverse effects, Rilpivirine administration & dosage, Rilpivirine adverse effects
- Abstract
Objectives: To compare efficacy, safety, tolerability, and patient-reported outcomes between two single-tablet regimens, rilpivirine/emtricitabine/tenofovir disoproxil fumarate (RPV/FTC/TDF) and efavirenz/emtricitabine/tenofovir disoproxil fumarate (EFV/FTC/TDF), in HIV-1-infected, treatment-naive adults., Design: This was a phase 3b, 96-week, randomized, open-label, international, noninferiority trial., Methods: A total of 799 participants were randomized (1 : 1) to receive RPV/FTC/TDF or EFV/FTC/TDF. The primary efficacy endpoint evaluated proportions of participants with HIV-1 RNA less than 50 copies/ml using the Snapshot algorithm. Additional assessments included CD4 cell counts, genotypic/phenotypic resistance, adverse events, patient-reported outcomes, and quality of life questionnaires., Results: At week 96, trial completion rates were 80.2% (316/394; RPV/FTC/TDF) and 74.0% (290/392; EFV/FTC/TDF). Overall, RPV/FTC/TDF was noninferior to EFV/FTC/TDF [HIV-1 RNA <50 copies/ml: 77.9 vs. 72.4%, respectively; difference -5.5; 95%CI (-0.6, 11.5); P = 0.076]. RPV/FTC/TDF was significantly more efficacious compared with EFV/FTC/TDF in participants with baseline HIV-1 RNA equal to or less than 100 000 copies/ml (78.8 vs. 71.2%; P = 0.046) and in those with CD4 cell count greater than 200 cells/μl (80.6 vs. 73.0%; P = 0.018). There was no significant between-group difference in the CD4 cell count increase (278 ± 189 vs. 259 ± 191 cells/μl; P = 0.17). Few participants developed resistance after week 48 (1.0% RPV/FTC/TDF; 0.3% EFV/FTC/TDF). Compared with EFV/FTC/TDF, RPV/FTC/TDF was associated with fewer adverse event-related discontinuations (3.0 vs. 11.0%; P<0.001), significantly fewer adverse events due to central nervous system issues and rash, greater improvements in patient-reported symptoms, and significant improvements in the SF-12v2 quality of life questionnaire mental health composite score (P = 0.014)., Conclusion: In treatment-naive, HIV-1-infected participants, 96-week RPV/FTC/TDF treatment demonstrated noninferior efficacy and better tolerability than EFV/FTC/TDF.
- Published
- 2016
- Full Text
- View/download PDF
5. Letter to the editor.
- Author
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Goldberg YP, Cohen CJ, Namdari R, Price N, Cadieux JA, Young C, Sherrington R, and Pimstone SN
- Subjects
- Female, Humans, Male, Erythromelalgia drug therapy, Sodium Channel Blockers therapeutic use, Sodium Channels genetics
- Published
- 2014
- Full Text
- View/download PDF
6. Week 96 efficacy and safety of rilpivirine in treatment-naive, HIV-1 patients in two Phase III randomized trials.
- Author
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Cohen CJ, Molina JM, Cassetti I, Chetchotisakd P, Lazzarin A, Orkin C, Rhame F, Stellbrink HJ, Li T, Crauwels H, Rimsky L, Vanveggel S, Williams P, and Boven K
- Subjects
- Adolescent, Adult, Aged, Alkynes, Antiretroviral Therapy, Highly Active adverse effects, Antiretroviral Therapy, Highly Active methods, Benzoxazines administration & dosage, Benzoxazines adverse effects, Cyclopropanes, Drug-Related Side Effects and Adverse Reactions epidemiology, Drug-Related Side Effects and Adverse Reactions pathology, Female, HIV Infections virology, Humans, Male, Middle Aged, Rilpivirine, Treatment Outcome, Young Adult, Anti-HIV Agents administration & dosage, Anti-HIV Agents adverse effects, HIV Infections drug therapy, HIV-1 isolation & purification, Nitriles administration & dosage, Nitriles adverse effects, Pyrimidines administration & dosage, Pyrimidines adverse effects
- Abstract
Background: In the week 48 primary analysis of ECHO and THRIVE, rilpivirine demonstrated noninferior efficacy and more favourable tolerability versus efavirenz in treatment-naive, HIV-1-infected adults. Pooled 96-week results are presented., Methods: Patients (N = 1368) received rilpivirine 25 mg once-daily (q.d.) or efavirenz 600 mg q.d., with two background nucleoside/nucleotide reverse transcriptase inhibitors, in two randomized, double-blind, double-dummy Phase III trials., Results: At week 96, response rate (% confirmed viral load <50 copies/ml; intent-to-treat, time-to-loss-of-virologic response) was 78% in both groups. Responses were similar for both treatments by background regimen, sex, race, and in patients with more than 95% adherence (M-MASRI) or baseline viral load 100,000 copies/ml or less. Responses were lower and virologic failure higher for rilpivirine versus efavirenz in patients with 95% or less adherence or baseline viral load more than 100,000 copies/ml. Beyond week 48, the incidence of virologic failure was comparable (3 versus 2%) between treatment groups, rilpivirine resistance-associated mutations were consistent with those observed in year 1, there were few adverse events in both groups and no new safety concerns. Over 96 weeks, discontinuations due to adverse events (4 versus 9%), treatment-related grade 2-4 adverse events (17 versus 33%), rash (4 versus 15%), dizziness (8 versus 27%) and abnormal dreams/nightmares (8 versus 13%), and grade 2-4 lipid abnormalities were lower with rilpivirine than efavirenz. Only 2 and 4% of patients in the rilpivirine and efavirenz treatment groups, respectively, reported at least possibly treatment-related grade 2-4 adverse events during the second year of treatment., Conclusions: Rilpivirine 25 mg q.d. and efavirenz 600 mg q.d. had comparable responses at week 96. Rilpivirine had more virologic failures but improved tolerability versus efavirenz. The majority of virologic failures occurred in the first 48 weeks.
- Published
- 2013
- Full Text
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7. Efficacy and safety of etravirine (TMC125) in treatment-experienced HIV-1-infected patients: 48-week results of a phase IIb trial.
- Author
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Cohen CJ, Berger DS, Blick G, Grossman HA, Jayaweera DT, Shalit P, Thompson M, Peeters M, de Béthune MP, Voorspoels E, Mack R, and Woodfall B
- Subjects
- Anti-HIV Agents adverse effects, Anti-HIV Agents therapeutic use, Dose-Response Relationship, Drug, HIV Infections virology, Humans, Nitriles, Pyridazines adverse effects, Pyridazines therapeutic use, Pyrimidines, Single-Blind Method, Treatment Outcome, Viral Load, Anti-HIV Agents administration & dosage, HIV Infections drug therapy, HIV-1 isolation & purification, Pyridazines administration & dosage
- Abstract
Forty-eight-week results from a randomized, multicentre, part-blinded, phase IIb clinical trial assessing the efficacy and safety of 400 and 800 mg etravirine twice daily (phase IIb formulation) and optimized background regimen versus standard-of-care regimen are presented. Both etravirine doses demonstrated sustained virological suppression at 48 weeks and a favourable tolerability profile. Etravirine demonstrated higher efficacy than control, irrespective of the number of detectable nonnucleoside reverse transcriptase inhibitor-resistance-associated mutations at baseline or active background antiretrovirals.
- Published
- 2009
- Full Text
- View/download PDF
8. T-cell receptor gene therapy of established tumors in a murine melanoma model.
- Author
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Abad JD, Wrzensinski C, Overwijk W, De Witte MA, Jorritsma A, Hsu C, Gattinoni L, Cohen CJ, Paulos CM, Palmer DC, Haanen JB, Schumacher TN, Rosenberg SA, Restifo NP, and Morgan RA
- Subjects
- Animals, CD8-Positive T-Lymphocytes immunology, CD8-Positive T-Lymphocytes metabolism, CD8-Positive T-Lymphocytes transplantation, Cell Line, Tumor, Coculture Techniques, Genetic Vectors genetics, Immunophenotyping, Interferon-gamma metabolism, Lymphocyte Activation immunology, Lymphocytes immunology, Lymphocytes metabolism, Melanoma, Experimental immunology, Melanoma, Experimental pathology, Membrane Glycoproteins genetics, Membrane Glycoproteins immunology, Mice, Mice, Inbred C57BL, Mice, Transgenic, Receptors, Antigen, T-Cell immunology, Receptors, Antigen, T-Cell, alpha-beta genetics, Receptors, Antigen, T-Cell, alpha-beta immunology, Receptors, Antigen, T-Cell, alpha-beta metabolism, Spleen cytology, Spleen immunology, Transfection, gp100 Melanoma Antigen, Genetic Therapy methods, Immunotherapy, Adoptive methods, Melanoma, Experimental therapy, Receptors, Antigen, T-Cell genetics
- Abstract
Adoptive cell transfer therapy using tumor-infiltrating lymphocytes for patients with metastatic melanoma has demonstrated significant objective response rates. One major limitation of these current therapies is the frequent inability to isolate tumor-reactive lymphocytes for treatment. Genetic engineering of peripheral blood lymphocytes with retroviral vectors encoding tumor antigen-specific T-cell receptors (TCRs) bypasses this restriction. To evaluate the efficacy of TCR gene therapy, a murine treatment model was developed. A retroviral vector was constructed encoding the pmel-1 TCR genes targeting the B16 melanoma antigen, gp100. Transduction of C57BL/6 lymphocytes resulted in efficient pmel-1 TCR expression. Lymphocytes transduced with this retrovirus specifically recognized gp100-pulsed target cells as measured by interferon-gamma secretion assays. Upon transfer into B16 tumor-bearing mice, the genetically engineered lymphocytes significantly slowed tumor development. The effectiveness of tumor treatment was directly correlated with the number of TCR-engineered T cells administered. These results demonstrated that TCR gene therapy targeting a native tumor antigen significantly delayed the growth of established tumors. When C57BL/6 lymphocytes were added to antigen-reactive pmel-1 T cells, a reduction in the ability of pmel-1 T cell to treat B16 melanomas was seen, suggesting that untransduced cells may be deleterious to TCR gene therapy. This model may be a powerful tool for evaluating future TCR gene transfer-based strategies.
- Published
- 2008
- Full Text
- View/download PDF
9. Efficacy and safety of etravirine (TMC125) in patients with highly resistant HIV-1: primary 24-week analysis.
- Author
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Nadler JP, Berger DS, Blick G, Cimoch PJ, Cohen CJ, Greenberg RN, Hicks CB, Hoetelmans RM, Iveson KJ, Jayaweera DS, Mills AM, Peeters MP, Ruane PJ, Shalit P, Schrader SR, Smith SM, Steinhart CR, Thompson M, Vingerhoets JH, Voorspoels E, Ward D, and Woodfall B
- Subjects
- Adult, CD4 Lymphocyte Count, Dreams drug effects, Drug Administration Schedule, Drug Resistance, Viral, Female, Humans, Male, Middle Aged, Mood Disorders chemically induced, Mutation, Nitriles, Pyridazines adverse effects, Pyrimidines, RNA, Viral blood, Reverse Transcriptase Inhibitors adverse effects, Treatment Outcome, Viral Load, HIV Infections drug therapy, HIV-1 drug effects, HIV-1 genetics, Pyridazines administration & dosage, Reverse Transcriptase Inhibitors administration & dosage
- Abstract
Objective: TMC125-C223 is an open-label, partially blinded, randomized clinical trial to evaluate the efficacy and safety of two dosages of etravirine (TMC125), a non-nucleoside reverse transcriptase inhibitor (NNRTI) with activity against wild-type and NNRTI-resistant HIV-1., Design: A total of 199 patients were randomly assigned 2: 2: 1 to twice-daily etravirine 400 mg, 800 mg and control groups, respectively. The primary endpoint was a change in viral load from baseline at week 24 in the intention-to-treat population., Methods: Patients had HIV-1 with genotypic resistance to approved NNRTIs and at least three primary protease inhibitor (PI) mutations. Etravirine groups received an optimized background of at least two approved antiretroviral agents [nucleoside reverse transcriptase inhibitors (NRTI) and/or lopinavir/ritonavir and/or enfuvirtide]. Control patients received optimized regimens of at least three antiretroviral agents (NRTIs or PIs and/or enfuvirtide)., Results: The mean change from baseline in HIV-1 RNA at week 24 was -1.04, -1.18 and -0.19 log10 copies/ml for etravirine 400 mg twice a day, 800 mg twice a day and the control group, respectively (P < 0.05 for both etravirine groups versus control). Etravirine showed no dose-related effects on safety and tolerability. No consistent pattern of neuropsychiatric symptoms was observed. There were few hepatic adverse events, and rashes were predominantly early onset and mild to moderate in severity., Conclusion: Etravirine plus an optimized background significantly reduced HIV-1-RNA levels from baseline after 24 weeks in patients with substantial NNRTI and PI resistance, and demonstrated a favorable safety profile compared with control.
- Published
- 2007
- Full Text
- View/download PDF
10. A randomized trial assessing the impact of phenotypic resistance testing on antiretroviral therapy.
- Author
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Cohen CJ, Hunt S, Sension M, Farthing C, Conant M, Jacobson S, Nadler J, Verbiest W, Hertogs K, Ames M, Rinehart AR, and Graham NM
- Subjects
- Adult, Aged, CD4 Lymphocyte Count, Female, HIV Infections immunology, HIV Infections virology, HIV-1 immunology, Humans, Male, Middle Aged, Phenotype, Practice Guidelines as Topic, Prospective Studies, RNA, Viral blood, RNA, Viral drug effects, Treatment Outcome, United States, Viral Load, Anti-HIV Agents therapeutic use, Drug Resistance, Viral, HIV Infections drug therapy, HIV Protease Inhibitors therapeutic use, HIV-1 drug effects, Reverse Transcriptase Inhibitors therapeutic use
- Abstract
Objective: To compare the effect of treatment decisions guided by phenotypic resistance testing (PRT) or standard of care (SOC) on short-term virological response., Design: A prospective, randomized, controlled clinical trial conducted in 25 university and private practice centers in the United States., Participants: A total of 272 subjects who failed to achieve or maintain virological suppression (HIV-1-RNA plasma level > 2000 copies/ml) with previous exposure to two or more nucleoside reverse transcriptase inhibitors and one protease inhibitor., Interventions: Randomization was to antiretroviral therapy guided by PRT or SOC., Main Outcome Measures: The percentage of subjects with HIV-1-RNA plasma levels less than 400 copies/ml at week 16 (primary); change from baseline in HIV-1-RNA plasma levels and number of "active" (less than fourfold resistance) antiretroviral agents used (secondary)., Results: At week 16, using intent-to-treat (ITT) analysis, a greater proportion of subjects had HIV-1-RNA levels less than 400 copies/ml in the PRT than in the SOC arm (P = 0.036, ITT observed; P = 0.079, ITT missing equals failure). An ITT observed analysis showed that subjects in the PRT arm had a significantly greater median reduction in HIV-1-RNA levels from baseline than the SOC arm (P = 0.005 for 400 copies/ml; P = 0.049 for 50 copies/ml assay detection limit). Significantly more subjects in the PRT arm were treated with two or more "active" antiretroviral agents than in the SOC arm (P = 0.003)., Conclusion: Antiretroviral treatment guided prospectively by PRT led to the increased use of "active" antiretroviral agents and was associated with a significantly better virological response.
- Published
- 2002
- Full Text
- View/download PDF
11. Vacuum-assisted closure in the treatment of complex gynecologic wound failures.
- Author
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Argenta PA, Rahaman J, Gretz HF 3rd, Nezhat F, and Cohen CJ
- Subjects
- Adult, Aged, Bandages, Female, Humans, Hysterectomy, Omentum surgery, Ovariectomy, Wound Healing, Surgical Wound Dehiscence therapy, Vacuum
- Abstract
Background: Complex wound failures are a source of significant morbidity and mortality. They are costly and time consuming to treat, and may evolve into chronic, debilitating conditions. Vacuum-assisted closure is a novel wound healing technique applying subatmospheric pressure to wounds to expedite healing., Cases: We report the successful use of vacuum-assisted closure therapy on three patients on a gynecologic oncology service with complex wound failures of various chronicity. In all cases, vacuum-assisted closure therapy was well tolerated and demonstrated efficacy within 48 hours of initiation., Conclusion: We conclude that vacuum-assisted closure therapy should be included in the armamentarium of the gynecologist addressing complex wound failures.
- Published
- 2002
- Full Text
- View/download PDF
12. Laparoscopic management of adnexal masses in premenopausal and postmenopausal women.
- Author
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Dottino PR, Levine DA, Ripley DL, and Cohen CJ
- Subjects
- Adnexal Diseases diagnosis, Female, Humans, Intraoperative Complications, Laparotomy, Middle Aged, Ovarian Neoplasms diagnosis, Ovarian Neoplasms surgery, Postoperative Complications, Adnexal Diseases surgery, Laparoscopy adverse effects, Postmenopause, Premenopause
- Abstract
Objective: To evaluate the feasibility and safety of laparoscopic adnexal mass removal in patients without preselection for benign pathology and assess the operative complications and findings., Methods: All patients presenting to the gynecologic oncology service between April 1992 and April 1996 with adnexal masses were candidates for laparoscopic management. Patients underwent preoperative radiological studies and office pelvic examination. Laparoscopic management was attempted on patients without evidence of gross metastatic disease or masses that extended above the umbilicus. Laparotomy was performed if indicated by pathologic findings or technical difficulty. All removed adnexal masses were sent for immediate pathologic diagnosis. The type of procedure, intraoperative findings, and complications were all recorded at the time of procedure., Results: One hundred sixty patients underwent laparoscopic evaluation for an adnexal mass. Benign pathology was discovered in 139 (87%, 95% confidence interval [CI] 84, 90) patients, and 141 (88%, 95% CI 86, 91) patients were managed laparoscopically. Reasons for laparotomy included technical difficulty, operative complications, or malignancy. Frozen section diagnosis was concordant with the final pathology reports in all but five patients (97% concordance), and no discrepancies resulted in treatment delays., Conclusion: Laparoscopic management of adnexal masses can be successful in a gynecologic oncology population if there is expertise in operative laparoscopy, availability of immediate accurate pathologic examination, and appropriate further treatment where indicated.
- Published
- 1999
- Full Text
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13. Prophylaxis for disseminated Mycobacterium avium complex (MAC) infection in patients with AIDS: a cost-effectiveness analysis.
- Author
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Freedberg KA, Cohen CJ, and Barber TW
- Subjects
- Cost-Benefit Analysis, Health Care Costs, Humans, Probability, Quality of Life, AIDS-Related Opportunistic Infections prevention & control, Mycobacterium avium-intracellulare Infection prevention & control
- Abstract
Objective: To determine the effectiveness and costs of prophylaxis for disseminated Mycobacterium avium complex (MAC) infection in patients with AIDS., Design: A decision analysis model was constructed to compare rifabutin (300 mg/day), azithromycin (1200 mg/week), and clarithromycin (500 mg twice per day) with no prophylaxis. Sensitivity analysis was done on all model parameters, including initial CD4 count for beginning prophylaxis., Setting: The setting was hypothetical for the cost-effectiveness model. Clinical data were taken from published prospective randomized controlled trials., Main Outcome Measures: Outcomes were measured in terms of projected life expectancy, quality-adjusted life expectancy, direct medical costs, and cost-effectiveness in U.S. dollars per quality-adjusted life-year saved ($/QALY)., Results: For patients with AIDS and those having CD4 counts <75 cells/mm3, azithromycin, clarithromycin, and rifabutin prophylaxis increased lifetime per person MAC-related costs by $994, $2,117, and $2,185 U.S., respectively. Quality-adjusted life expectancy increased from 1.6068 QALYs to between 1.6186 and 1.6255 QALYs. The cost-effectiveness ratios were $58,200, $116,000, and $179,100/QALY saved for azithromycin, clarithromycin, and rifabutin prophylaxis, respectively, each compared with no prophylaxis. Results were most dependent on the annual cost of prophylaxis, the initial CD4 count when starting prophylaxis, and any survival benefit with prophylaxis. For each type of prophylaxis, strategies beginning with CD4 counts <25 or 50 cells/mm3 were substantially more cost-effective than those beginning in patients with higher CD4 counts., Conclusions: MAC prophylaxis is likely to cost society an additional $99 to $219 million U.S. per 100,000 patients treated. In the context of Centers for Disease Control and Prevention (CDC) recommendations to use prophylaxis in patients with CD4 counts <75 cells/mm3, azithromycin represents the best value and is most cost-effective when used in patients with CD4 counts <25 cells/mm3.
- Published
- 1997
- Full Text
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14. Managed care in gynecologic oncology.
- Author
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Cohen CJ and Ripley D
- Subjects
- Contract Services, Family Practice, Female, Humans, Physician-Patient Relations, Genital Neoplasms, Female therapy, Gynecology organization & administration, Managed Care Programs organization & administration, Medical Oncology organization & administration
- Abstract
We review the recent literature on managed care and its application to gynecologic oncology. Although the literature is limited, we discuss professional agreement contracts, the role of primary care physicians and specialists in gynecologic cancer screening, changes in health care distribution, changes in physician-patient relationships, and cancer research.
- Published
- 1996
15. Pediatrics in an inner city environment: a practice responds to the challenges of the 1990s.
- Author
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Cohen CJ and Thébèrge R
- Subjects
- Adolescent, Adolescent Health Services organization & administration, Child, Child Health Services organization & administration, Group Practice trends, Humans, Insurance, Health, Reimbursement economics, Insurance, Health, Reimbursement trends, Massachusetts, Organizational Innovation, Personnel Staffing and Scheduling statistics & numerical data, Personnel Staffing and Scheduling trends, Urban Health, Group Practice organization & administration, Pediatrics organization & administration, Practice Management, Medical trends
- Published
- 1993
- Full Text
- View/download PDF
16. The concept of uterine preservation with ovarian malignancies.
- Author
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Navot D, Fox JH, Williams M, Brodman M, Friedman F Jr, and Cohen CJ
- Subjects
- Adult, Female, Humans, Infant, Newborn, Male, Omentum surgery, Ovariectomy, Pregnancy, Pregnancy Outcome, Twins, Cystadenocarcinoma surgery, Embryo Transfer methods, Estrogen Replacement Therapy, Ovarian Neoplasms surgery, Uterus
- Abstract
A 30-year-old woman with bilateral, recurrent, borderline papillary serous cystadenocarcinoma of the ovary was treated with bilateral oophorocystectomy and omentectomy with uterine preservation. Ten years later, through induction of an artificial endometrial cycle and ovum donation, she conceived twins and delivered two healthy infants. Staging exploratory laparotomy at the time of cesarean delivery was negative for malignancy. This case illustrates the value of uterine preservation for cases in which classical teaching has indicated hysterectomy with bilateral salpingoophorectomy.
- Published
- 1991
17. Clinical features and treatment outcome of patients with epithelial carcinoma of the ovary metastatic to the central nervous system.
- Author
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Plaxe SC, Dottino PR, Lipsztein R, Dalton J, and Cohen CJ
- Subjects
- Aged, Antigens, Tumor-Associated, Carbohydrate metabolism, Brain Neoplasms diagnosis, Brain Neoplasms mortality, Brain Neoplasms therapy, Combined Modality Therapy, Female, Humans, Lymphatic Metastasis, Meningeal Neoplasms secondary, Middle Aged, Neoplasm Staging, Prognosis, Tomography, X-Ray Computed, Brain Neoplasms secondary, Ovarian Neoplasms therapy
- Abstract
Involvement of the central nervous system with carcinoma of the ovary is being noted with increasing frequency. We report on six patients who presented with central nervous system metastases between 2-61 months after diagnosis. Five patients had elevated serum CA 125 values at the time of diagnosis of central nervous system disease and presenting symptoms, and findings on neurologic examination generally correlated with computed tomography-documented lesions. Eighty-three percent of our patients were symptomatically relieved with a course of 30 Gy given to the whole brain; however, there were no long-term survivors (range 2-24 months). Survival did not appear prolonged in the four patients who received systemic chemotherapy as well as whole-brain irradiation.
- Published
- 1990
18. Treatment of advanced adenocarcinoma of the endometrium with melphalan, 5-fluorouracil, and medroxyprogesterone acetate: a preliminary study.
- Author
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Cohen CJ, Deppe G, and Bruckner HW
- Subjects
- Aged, Drug Therapy, Combination, Female, Humans, Middle Aged, Adenocarcinoma drug therapy, Fluorouracil therapeutic use, Medroxyprogesterone therapeutic use, Melphalan therapeutic use, Uterine Neoplasms drug therapy
- Abstract
Combination chemotherapy can produce a rapid and frequent therapeutic effect against advanced endometrial adenocarcinoma regardless of the tumor distribution. A new treatment program is described. Melphalan, 5-fluorouracil, and medroxyprogesterone acetate achieved 6 of 7 objective responses in patients. This result with combination chemotherapy is substantially better than results with single agents or hormones alone and justifies further evaluation of combinations of cytotoxic chemotherapy as part of the initial treatment of choice for patients with advanced endometrial adenocarcinoma.
- Published
- 1977
19. Combination chemotherapy for advanced carcinoma of the fallopian tube.
- Author
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Deppe G, Bruckner HW, and Cohen CJ
- Subjects
- Cisplatin administration & dosage, Cyclophosphamide administration & dosage, Doxorubicin administration & dosage, Drug Therapy, Combination, Female, Humans, Middle Aged, Progestins administration & dosage, Adenocarcinoma drug therapy, Antineoplastic Agents administration & dosage, Fallopian Tube Neoplasms drug therapy
- Abstract
Two patients with advanced adenocarcinoma of the fallopian tube were treated with cis-diamminedichloroplatinum, adriamycin, and progestins. Cyclophosphamide was added to the treatment of 1 patient. Both regimens achieved surgically proved complete remission. No severe drug-related toxicity occurred.
- Published
- 1980
20. Cerebral blindness in association with cis-platinum chemotherapy for advanced carcinoma of the fallopian tube.
- Author
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Diamond SB, Rudolph SH, Lubicz SS, Deppe G, and Cohen CJ
- Subjects
- Cisplatin administration & dosage, Doxorubicin administration & dosage, Drug Therapy, Combination, Evoked Potentials, Visual, Female, Humans, Middle Aged, Neoplasm Metastasis, Adenocarcinoma, Papillary drug therapy, Blindness chemically induced, Cisplatin adverse effects, Fallopian Tube Neoplasms drug therapy
- Abstract
A 62-year-old woman with a diagnosis of metastatic fallopian tube carcinoma was treated with cis-platinum and doxorubicin (Adriamycin) at a dosage of 50 mg/m2 intravenously every 3 weeks. After the 10th course of cis-platinum and doxorubicin, she complained of headache and inability to see. Physical examination was compatible with cortical blindness. The brain scan and computed tomographic scan were normal. Visual evoked potentials showed a delay in latency. Visual acuity completely returned over the next months, but right homonymous hemianopia persists. The temporal relationship between the findings and the treatment with platinum implicates this drug as the possible causative agent in the cortical blindness.
- Published
- 1982
21. Treatment of recurrent and persistent germ cell tumors with cisplatin, vinblastine, and bleomycin.
- Author
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Jacobs AJ, Harris M, Deppe G, DasGupta I, and Cohen CJ
- Subjects
- Adolescent, Adult, Bleomycin administration & dosage, Child, Cisplatin administration & dosage, Drug Therapy, Combination, Female, Humans, Neoplasm Recurrence, Local, Vinblastine administration & dosage, Antineoplastic Agents administration & dosage, Antineoplastic Combined Chemotherapy Protocols, Dysgerminoma drug therapy, Ovarian Neoplasms drug therapy
- Abstract
Four patients were treated with vinblastine, cisplatin, and bleomycin for recurrent or persistent germ cell tumors. In all patients a clinical response was achieved. In 2 patients complete response was attained and they are free of disease following second-look laparotomy. One had a mixed germ cell tumor that persisted as dysgerminoma following primary chemotherapy. The other was a true hermaphrodite with pure dysgerminoma. In patients with endodermal sinus tumor transient response was achieved, but the tumors recurred and the patients died within 6 months.
- Published
- 1982
22. Prognostic factors: cisplatin regimens for patients with ovarian cancer after failure of chemotherapy.
- Author
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Bruckner HW, Cohen CJ, Feuer E, Wallach RC, Kabakow B, and Holland JF
- Subjects
- Adult, Altretamine administration & dosage, Cisplatin administration & dosage, Cyclophosphamide administration & dosage, Doxorubicin administration & dosage, Drug Administration Schedule, Female, Humans, Middle Aged, Ovarian Neoplasms mortality, Prognosis, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Cisplatin therapeutic use, Ovarian Neoplasms drug therapy
- Abstract
For 129 ovarian cancer patients failing prior chemotherapy, overall clinical response rates were: 21% with cisplatin, 36% with cisplatin plus doxorubicin, 52% with cyclophosphamide added to the two drugs, and 44% with hexamethylmelamine added to the three drugs. Median survival was six or seven months in each trial. Twenty-five percent of the patients survived nine months with cisplatin and 14 to 16 months with each of the three combinations. Characteristics associated with best rate of response included: performance status 1 (completely ambulatory), age greater than or equal to 50, residual tumor less than or equal to 5 cm, and two or less prior cytotoxic drugs. In multivariate analyses, performance status dominated, although age and possibly treatment (cisplatin versus others) were significant. With performance status removed from the model, all of the remaining factors became significant. Factors associated with best survival included: performance status 1, tumor size less than or equal to 5 cm, and complete or partial response. In a multivariate analysis for survival, performance status entered the model. In a series of analyses with performance status removed, tumor size or response entered the model. These findings provide reasons to study both treatment with cisplatin before disease progression reduces the number of favorable characteristics and systematic second attempts at debulking surgery.
- Published
- 1987
23. Dysgerminoma of the ovary associated with true hermaphroditism.
- Author
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Schwartz IS, Cohen CJ, and Deligdisch L
- Subjects
- Adult, Disorders of Sex Development pathology, Dysgerminoma pathology, Female, Humans, Ovarian Neoplasms pathology, Ovary pathology, Disorders of Sex Development complications, Dysgerminoma complications, Ovarian Neoplasms complications
- Abstract
A dysgerminoma of the left gonad exhibiting malignant features was diagnosed at laparotomy in a 33-year-old virginal phenotypic female who had a normal menstrual history. Pathologic examination of the contralateral (right) gonad revealed an ovotestis. The nonaffected residual portion of the tumor-bearing left gonad exhibited only ovarian stroma. The ovotestis was characterized by a nodule of testicular parenchyma composed of partly hyalinized seminiferous tubules without evident spermatogenesis. The ovotestis was contiguous to normal ovarian elements, including a cystic corpus luteum and primordial follicles. Proliferative endometrium was found lining the small uterus. The findings are indicative of true hermaphroditism. The occurrence of dysgerminoma and other tumors in association with various forms of gonadl dysgenesis is discussed. To the authors' knowledge, this is the first reported case of dysgerminoma occurring in a phenotypic female hermaphrodite.
- Published
- 1980
24. Extrauterine pelvic malignant mixed mesodermal tumors. A study of 10 cases with immunohistochemistry.
- Author
-
Deligdisch L, Plaxe S, and Cohen CJ
- Subjects
- Aged, Aged, 80 and over, Carcinoma, Papillary analysis, Desmin analysis, Diagnosis, Differential, Female, Humans, Immunohistochemistry, Keratins analysis, Middle Aged, Myoglobin analysis, Neoplasms, Germ Cell and Embryonal analysis, Ovarian Neoplasms analysis, Pelvic Neoplasms analysis, Vimentin analysis, Carcinoma, Papillary pathology, Neoplasms, Germ Cell and Embryonal pathology, Ovarian Neoplasms pathology, Pelvic Neoplasms pathology
- Abstract
Ten cases of extrauterine malignant mixed mesodermal tumors (MMMTs), nine ovarian, and one pelvic, are presented. One patient had a purely epithelial primary ovarian tumor and MMMT in her recurrent tumors. All the other patients had MMMT in their primary and recurrent tumors. Eight patients had heterologous MMMT including cartilage, striated muscle, and adipose tissue in one case. Two patients had homologous MMMT. All cases presented with metastases involving abdominal organs that were either MMMT or epithelial neoplasms and MMMT. Five patients had recurrent tumors, one extensively involving the spleen. In all recurrent tumors, the mesenchymal components were considerably more abundant than in the primary tumors. Immunohistologic studies of intermediate filaments were performed in seven cases, revealing cytokeratin-positive epithelial structures, vimentin-positive mesenchymal (including cartilaginous) structures, as well as coexpression of cytokeratin and vimentin in anaplastic and giant tumor cells in some cases. Some anaplastic spindle cells, which on routine stains were suggestive of stromal cells, stained positive for cytokeratin, thus identifying their epithelial nature. Desmin staining performed in five cases showed positive staining of rhabdomyoblasts in only one case. Myoglobin staining performed in seven cases was positive in four. The histogenesis from primitive müllerian structures and the natural history of these uncommon neoplasms are discussed in light of the pathological and immunohistochemical data presented.
- Published
- 1988
- Full Text
- View/download PDF
25. A dihydropyridine (Bay k 8644) that enhances calcium currents in guinea pig and calf myocardial cells. A new type of positive inotropic agent.
- Author
-
Thomas G, Chung M, and Cohen CJ
- Subjects
- 3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester, Action Potentials drug effects, Animals, Calcium Channel Blockers pharmacology, Cattle, Cells, Cultured, Electric Stimulation, Female, Guinea Pigs, Isoproterenol pharmacology, Male, Myocardium cytology, Nifedipine pharmacology, Nisoldipine, Nitrendipine, Purkinje Fibers drug effects, Stimulation, Chemical, Strontium pharmacology, Time Factors, Calcium metabolism, Ion Channels drug effects, Myocardial Contraction drug effects, Nifedipine analogs & derivatives
- Abstract
Bay k 8644 is a structural analog of nifedipine with positive inotropic activity. The mechanism of drug action was evaluated by measuring the effects of Bay k 8644 on twitch tension, action potential configuration, and calcium channel currents in myocardial cells. Bay k 8644 increases twitch tension in guinea pig atria without changing the time course of tension development. The drug does not occlude the effect of isoproterenol on twitch tension. The effects of Bay k 8644 on atrial twitch tension are highly dependent on the frequency of stimulation. Maximal inotropic effects are observed at approximately 0.5 Hz, but no inotropic effect occurs at 0.003 Hz (a rested-state contraction). Since positive inotropic effects only occur with frequent electrical stimulation, they are not due to an intracellular action or to mechanisms that elevate cell calcium in quiescent muscle, such as inhibition of the Na,K-ATPase. Bay k 8644 increases the action potential duration of calf ventricular muscle and Purkinje fibers. Effects on action potential duration are occluded by 1 microM nisoldipine, which specifically blocks calcium channels. The interaction of Bay k 8644 with calcium channels in calf Purkinje fibers was studied using the two-microelectrode voltage clamp technique. Strontium was used as a charge carrier to minimize current through calcium-activated channels and to avoid changes in calcium conductance due to changes in intracellular calcium. Bay k 8644 increases strontium currents and alters the time- and voltage-dependence of channel opening. The greatest percent increase in strontium current occurs for weak depolarizations. For strong depolarizations, strontium current is increased most at the beginning of a test pulse. The drug-induced changes in calcium channel gating are inconsistent with a calcium- or cyclic adenosine monophosphate-mediated effect, and indicate a novel mechanism of action on calcium channels. Thus, Bay k 8644 is the first positive inotropic agent shown to act specifically and directly on calcium channels.
- Published
- 1985
- Full Text
- View/download PDF
26. Increase in intracellular sodium ion activity during stimulation in mammalian cardiac muscle.
- Author
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Cohen CJ, Fozzard HA, and Sheu SS
- Subjects
- Animals, Cardiac Pacing, Artificial, Electrocardiography methods, Guinea Pigs, Heart Rate, Heart Ventricles metabolism, Ouabain pharmacology, Papillary Muscles metabolism, Purkinje Fibers metabolism, Rabbits, Sheep, Myocardial Contraction drug effects, Myocardium metabolism, Sodium metabolism
- Abstract
Changes in stimulation rate alter the electrical and mechanical characteristics of myocardial cells. We have investigated the possibility that intracellular sodium activity (aiNa) changes with stimulation and correlates with changes in contraction strength. Two kinds of liquid membrane Na+-selective microelectrodes were used to measure aiNa in guinea pig and sheep ventricular muscle and in sheep Purkinje strands. Stimulation produced a rate- and time-dependent elevation of aiNa. Small increases in aiNa were seen at stimulation rates as slow as 0.2 Hz, and faster rates of stimulation elevated aiNa by over 30%. The changes seen in Purkinje strands and ventricular muscle were similar. Following a period of stimulation, aiNa and Vm returned to their pre-stimulus levels with the same time courses. This is consistent with the suggestion that the post-stimulation hyperpolarization is the result of an increased rate of electrogenic Na+ extrusion. The effects of stimulation on aiNa and tension were compared with those of ouabain. The comparison suggests that rapid stimulation could produce increased contraction strength as the result of a substantial gain in intracellular calcium via a Na-Ca exchange mechanism, but that this is only one of several factors determining the force-frequency relationship.
- Published
- 1982
- Full Text
- View/download PDF
27. Multidrug treatment of advanced and recurrent endometrial carcinoma: a Gynecologic Oncology Group study.
- Author
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Cohen CJ, Bruckner HW, Deppe G, Blessing JA, Homesley H, Lee JH, and Watring W
- Subjects
- Adenocarcinoma mortality, Adult, Aged, Clinical Trials as Topic, Dose-Response Relationship, Drug, Drug Administration Schedule, Female, Humans, Middle Aged, Random Allocation, Uterine Neoplasms mortality, Adenocarcinoma drug therapy, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Neoplasm Recurrence, Local drug therapy, Uterine Neoplasms drug therapy
- Abstract
Patients (358) with advanced (FIGO stages III and IV) or recurrent endometrial cancer were treated with one of two regimens: 1) melphalan and 5-fluorouracil daily for four days, repeated every four weeks with megace daily for eight weeks and 2) adriamycin, 5-fluorouracil, and cyclophosphamide, intravenous bolus every 21 days with megace daily for eight weeks. All patients were randomized except for 63 with known cardiac disease who were assigned to regimen 1 (to avoid adriamycin) and studied separately. Stratification was effected for performance status, history of previous progestational therapy, presence or absence of measurable disease, and stage of disease. The objective response rate in those with measurable disease was 36.8% in both groups; 36.8% of each group had stable disease, and only 26.4% progressed on treatment. Response was unaffected by site of recurrence, time to first recurrence, presence or absence of previous treatment by progestational or radiation therapy, or age. Grade of tumor and performance status did affect response, although 44 of 57 objective responders had undifferentiated tumors. The two combinations achieved response rapidly, required careful supervision, and were especially useful in treating patients with usually poor prognostic features.
- Published
- 1984
28. Screening for endometrial cancer.
- Author
-
Cohen CJ and Gusberg SB
- Subjects
- Adenocarcinoma diagnosis, Biopsy methods, Biopsy, Needle methods, Carcinoma, Squamous Cell diagnosis, Cell Adhesion, Curettage instrumentation, Endometrial Hyperplasia diagnosis, Endometriosis pathology, Endometrium pathology, Female, Humans, Menstruation Disturbances pathology, Polyvinyls, Therapeutic Irrigation methods, Uterine Cervical Neoplasms diagnosis, Uterine Neoplasms pathology, Vacuum Curettage methods, Vaginal Smears, Uterine Neoplasms diagnosis
- Abstract
Since Gusberg's description in 1947 of adenomatous hyperplasia (15), the role of precursors in the development of endometrial carcinoma has been well studied. There is now no doubt that in many patients histologic precursors can be demonstrated in the endometrial cavity prior to the development of invasive cancer. At this point in the continuum, interruption by hysterectomy or other therapy will insure the patient's health. We have discussed a wide variety of techniques designed to provide cytologic or histologic samples of the endometrium that are highly effective in the detection of early neoplasia. As a goal, universal endometrial sampling on a periodic basis is probably impractical and may be unecessary or undesirable. However, surely the patient at high risk for endometrial cancer requires close periodic screening. The high-risk category may be expanded to include others beyond the group of hypertensive, diabetic, obese, anovulatory, nulliparous women. It should include patients with irregular vaginal bleeding, those with a strong family history of genital and breast cancer, those patients receiving hormone therapy, and patients in the menopausal years who experience changes in the menstrual pattern. With intelligent and aggressive application of outpatient screening, uterine cancer can be diagnosed when patients are virtually completely curable, thus resulting in further reduction in mortality from this disease.
- Published
- 1975
- Full Text
- View/download PDF
29. Adriamycin treatment of advanced vulvar carcinoma.
- Author
-
Deppe G, Bruckner HW, and Cohen CJ
- Subjects
- Aged, Carcinoma, Squamous Cell surgery, Female, Humans, Lymphatic Metastasis, Middle Aged, Neoplasm Recurrence, Local drug therapy, Vulvar Neoplasms surgery, Carcinoma, Squamous Cell drug therapy, Doxorubicin therapeutic use, Vulvar Neoplasms drug therapy
- Abstract
Four consecutive patients with measurable recurrent squamous cell carcinoma of the vulva were treated with Adriamycin, in small doses approximately 45 mg/square meter of body surface area every 3 weeks. Three patients achieved objective regression of nodal metastases and residual tumor with clinical subjective benefit. Tumor control was maintained for 32, 31+, and 28+ weeks.
- Published
- 1977
30. Common aspects of immunologic tolerance in pregnancy and malignancy.
- Author
-
Gleicher N, Deppe G, and Cohen CJ
- Subjects
- Antibody Formation, Antigen-Antibody Reactions, Antigens, Neoplasm immunology, Cell Migration Inhibition, Female, Fetus immunology, Graft Rejection, Humans, Immunity, Cellular, Immunoglobulins biosynthesis, Leukocytes immunology, Models, Biological, Placenta immunology, T-Lymphocytes immunology, Transplantation Immunology, Immune Tolerance, Neoplasms immunology, Pregnancy
- Abstract
The fetoplacental allograft and the malignant neoplasm represent the only 2 biologic conditions in which antigenic tissue is tolerated by a seemingly intact immune system. Recent investigations in the fields of tumor and pregnancy immunology have resulted in the recognition of a variety of immunologic mechanisms which are common to both systems. These common denominators are reviewed and a thesis suggesting a common mechanism in the nonrejection of pregnancy and malignancy, based on the presence of embryonic antigens in both systems, is presented.
- Published
- 1979
31. Endometrial carcinoma and oral contraceptive agents.
- Author
-
Cohen CJ and Deppe G
- Subjects
- Adult, Contraceptives, Oral, Sequential administration & dosage, Contraceptives, Oral, Sequential adverse effects, Contraceptives, Oral, Synthetic administration & dosage, Dimethisterone administration & dosage, Dimethisterone adverse effects, Drug Combinations, Estrogens, Conjugated (USP) administration & dosage, Estrogens, Conjugated (USP) adverse effects, Ethinyl Estradiol administration & dosage, Ethinyl Estradiol adverse effects, Female, Humans, Hyperplasia, Medroxyprogesterone administration & dosage, Medroxyprogesterone adverse effects, Middle Aged, Norgestrel administration & dosage, Norgestrel adverse effects, Time Factors, Adenocarcinoma chemically induced, Contraceptives, Oral adverse effects, Contraceptives, Oral, Synthetic adverse effects, Uterine Neoplasms chemically induced
- Abstract
Six patients who took oral contraceptive agents for 5 to 18 years developed endometrial neoplasia. Endometrial adenocarcinoma occurred in 4 of these patients and severe adenomatous hyperplasia occured in 2. Five of the 6 patients took sequential agents; 1 patient used a combined agent. An additional patient who took Premarin and Provera sequentially developed adenocarcinoma of the endometrium. Eighteen cases of endometrial adenocarcinoma and 7 cases of adenomatous hyperplasia in patients with long-term sequential oral contraceptive use have previously been reported by others. Progestogens may not be completely protective against the endometrial cancer-causing potential of the estrogens, especially in the sequential regimens.
- Published
- 1977
32. Maximal upstroke velocity as an index of available sodium conductance. Comparison of maximal upstroke velocity and voltage clamp measurements of sodium current in rabbit Purkinje fibers.
- Author
-
Cohen CJ, Bean BP, and Tsien RW
- Subjects
- Action Potentials, Animals, Anti-Arrhythmia Agents metabolism, Anti-Arrhythmia Agents physiology, Electrophysiology, Ion Channels metabolism, Kinetics, Purkinje Fibers metabolism, Rabbits, Temperature, Tetrodotoxin metabolism, Heart Conduction System physiology, Ion Channels physiology, Myocardium metabolism, Purkinje Fibers physiology, Sodium metabolism
- Abstract
We compared the maximal upstroke velocity of action potentials in short rabbit Purkinje fibers with sodium currents measured with a two-microelectrode voltage clamp. The number of sodium channels available to open during a sudden depolarization was varied either by blockade with tetrodotoxin or by inactivation with steady depolarizations. In both cases, the maximal upstroke velocity was found to be a very nonlinear measure of the number of available sodium channels. For example, 3 microM tetrodotoxin blocks 85% of the sodium channels, but reduces the maximal upstroke velocity by only 33%. Voltage clamp and upstroke velocity experiments were reconstructed with a computer model of the rabbit Purkinje fiber preparation that was closely based on experimental measurements of passive cable properties and sodium channel characteristics. The simulations indicate that our voltage clamp measurements of sodium current accurately report changes in channel availability, but they also show that the maximal upstroke velocity is a strongly nonlinear index of available sodium conductance. Most of the nonlinearity arises from the activation kinetics of the sodium channels: as the pool of available channels decreases, a greater percentage of those channels activate and contribute inward current at the time of the maximal upstroke velocity. Simulations predict that the maximal upstroke velocity-available sodium conductance relationship would still remain nonlinear at 37 degrees C or under different stimulus conditions that give uniform or continuously propagated action potentials. The nonlinearity may invalidate inferences based on earlier maximal upstroke velocity experiments: the existence of two types of sodium channels with different tetrodotoxin sensitivity, steady state voltage dependence of tetrodotoxin block, voltage range over which sodium channels inactivate, and rapid, then slow recovery of sodium channel availability following a sudden repolarization. All of these conclusions need to be reevaluated.
- Published
- 1984
- Full Text
- View/download PDF
33. Heterogeneity of intracellular potassium activity and membrane potential in hypoxic guinea pig ventricle.
- Author
-
Baumgarten CM, Cohen CJ, and McDonald TF
- Subjects
- Animals, Female, Guinea Pigs, Heart Ventricles physiopathology, Ion Exchange, Membrane Potentials drug effects, Microelectrodes, Oxygen physiology, Papillary Muscles physiopathology, Hypoxia physiopathology, Intracellular Membranes metabolism, Potassium metabolism
- Abstract
The relationship between membrane potential (Em) and the potassium equilibrium potential (EK) was investigated in hypoxic guinea pig papillary muscle. After more than 8 hours of hypoxia, cells with near normal Em (-86.2 +/- 0.9 mV) and action potentials were observed. However, the intracellular potassium concentration ([K+]i) based on chemical analysis and the assumption that potassium was homogeneously distributed was 41.8 +/- 4.3 mM; the apparent EK was -55.7 +/- 2.9 mV, significantly positive to Em. Measurements with potassium ion-selective microelectrodes revealed that prolonged hypoxia results in at least two populations of cells with different characteristics. The first population had an intracellular potassium activity (aiK) of 101.5 +/- 1.9 mM, and EK was 4.7 mV negative to Em. In contrast, EK was 33.4 +/- 1.3 mV negative to Em in the second population. These cells also exhibited a reduced sensitivity to changes in bath potassium, and calculations suggest aiK was about 18 mM. The existence of cell populations with a near normal and very low aiK can explain the intermediate value of [K+]i calculated assuming a homogenous potassium distribution. Cells with near normal Em and action potentials represent the population with near normal aiK. Hypoxia may also cause non-uniform changes in other cellular characteristics.
- Published
- 1981
- Full Text
- View/download PDF
34. Modulation and intensification of a cyclophosphamide, hexamethylmelamine, doxorubicin, and cisplatin ovarian cancer regimen.
- Author
-
Bruckner HW, Cohen CJ, Feuer E, and Holland JF
- Subjects
- Altretamine administration & dosage, Cisplatin administration & dosage, Cyclophosphamide administration & dosage, Doxorubicin administration & dosage, Female, Humans, Middle Aged, Ovarian Neoplasms mortality, Ovarian Neoplasms pathology, Antineoplastic Agents therapeutic use, Antineoplastic Combined Chemotherapy Protocols, Ovarian Neoplasms drug therapy
- Abstract
For 61 patients with stage III-IV carcinoma of the ovary, chemotherapy consisted first of cisplatin 50 mg/m2 on day 1, cyclophosphamide 500 mg/m2 on day 3, doxorubicin 50 mg/m2 on day 3, and hexamethylmelamine 100 mg/m2 on days 4-15 every 4 weeks. The dosages of doxorubicin and hexamethylmelamine were increased by 60 and 100%, respectively, until the nadir white blood cell counts fell to 1.0 x 10(9)/L. This regimen was less neurotoxic and nephrotoxic than other intensive treatments and produced better therapeutic effects than did the immediate preceding Mount Sinai regimens: 1) The overall median survival was 43 months and progression-free survival was 25 months; 2) the greatest benefit occurred among patients under 50 years of age; 3) regression of large tumors increased in frequency, with 33% of tumors 2-6 cm and 16% of tumors larger than 6 cm converted to either pathologically proved remission or microscopic disease; and 4) for the first time, partial surgical debulking producing residual tumors less than 6 cm in size improved early survival.
- Published
- 1989
35. Automated cytologic screening for uterine cancer. A feasibility study.
- Author
-
Gusberg SB, Cohen CJ, Yannopoulis K, Grand S, and Kardon P
- Subjects
- Computers statistics & numerical data, Female, Humans, Methods, Pattern Recognition, Automated, Cytodiagnosis instrumentation, Mass Screening, Uterine Neoplasms prevention & control
- Published
- 1969
36. Treatment problems in endometrial cancer.
- Author
-
Cohen CJ
- Subjects
- Age Factors, Cardiovascular Diseases complications, Colitis radiotherapy, Diverticulitis radiotherapy, Female, Hormones therapeutic use, Humans, Leiomyoma complications, Obesity complications, Pelvic Inflammatory Disease radiotherapy, Pregnancy, Pregnancy Complications, Tuberculosis, Female Genital radiotherapy, Uterine Hemorrhage therapy, Uterine Neoplasms complications, Uterine Neoplasms drug therapy, Uterine Prolapse radiotherapy, Uterine Rupture therapy, Endometrium, Uterine Neoplasms therapy
- Published
- 1967
- Full Text
- View/download PDF
37. Radiosensitivity testing; a modern adjuvant in the treatment of cervical cancer.
- Author
-
Cohen CJ and Gusberg SB
- Subjects
- Carcinoma, Squamous Cell radiotherapy, Female, Histocytochemistry, Humans, Methods, Microscopy, Electron, Prognosis, Uterine Cervical Neoplasms mortality, Radiotherapy Dosage, Uterine Cervical Neoplasms radiotherapy
- Published
- 1969
- Full Text
- View/download PDF
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