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Biomedical subjects

I Cohen

Publications and source records attributed to I Cohen.

At least 145 records · Page 8Linked to original sources

Different coexisting endometrial histological features in asymptomatic postmenopausal breast cancer patients treated with tamoxifen.

In an attempt to assess the hypothesis that different endometrial sites may respond differently to tamoxifen exposure in postmenopausal women, hysteroscopic selected endometrial histology was investigated in 175 postmenopausal breast cancer patients who received continuous treatment with tamoxifen, and in 27 similar patients not treated with tamoxifen who served as controls. In the tamoxifen-treated patients 14 (8.0%) developed endometrial polyps. Of 14 patients, 8 (57.2%) each displayed atrophic endometrium in the same histologic specimen, 5 (35.7%) each had coexisting simple hyperplasia, and 1 (7.1%) other had complex hyperplasia. Another 21 (12.0%) developed simple or complex hyperplasia. The endometrial hyperplasia coexisted with atrophic endometrium in all these patients. All these lesions were selectively identified by hysteroscopic examination prior to the endometrial biopsy. In the control group 3 (11.0%) had simple hyperplasia and 2 (7.4%) had endometrial polyps. The above results support the hypothesis that the endometrium of postmenopausal breast cancer patients on tamoxifen treatment may possess different responses to tamoxifen exposure.

Aged↗

Chlamydia trachomatis infection during pregnancy: can it cause an intrauterine infection?

In an attempt to prove the presence of intrauterine fetal chlamydial infection, sera from 26 laboring women, who tested positive for cervical chlamydial antigen in the first half of their pregnancies, and from 43 laboring women with no evidence of such infection, and sera from the cord of their delivered infants were tested for chlamydial IgA-, IgG- and IgM-specific antibodies. Nine (34.6%) of the 26 women with positive cervical infection and 5 (11.6%) of the 43 women with no identifiable cervical infection had significant antibody levels at the time of the delivery. Three of the 26 (11.5%) babies born to the mothers with positive cervical chlamydial infection early in the pregnancy and high antibody titer at delivery were found to have anti-chlamydial antibodies in their cord serum, indicating intrauterine infection; cord sera from the other 43 babies were negative for these antibodies. These findings suggest a low but possible risk of intrauterine infection in the presence of lower genital infection during pregnancy.

Adult↗

A community hospital experience with colonoscopic polypectomies.

This study analyzed 432 consecutive polypectomies performed in 279 patients in the gastroenterology unit of a community hospital. The patients were separated into 2 groups; group I--symptomatic patients considered suitable for colonoscopic examination, and group II--asymptomatic high-risk patients. The mean number of detected polyps was similar in both groups, the vast majority of the polyps in both groups were small (< 5 mm), and were mainly of tubular histology. Polyps in the rectosigmoid area were more common (56.6%) in the symptomatic patients than in the asymptomatic patients (44.1%). Fourteen percent of patients in group I and 33% in group II had no polyps within 60 cm from the anal verge. Carcinoma in situ was found in large polyps mainly in group I. Flat adenomas were not found in the studied population. The incidence of hyperplastic polyps was similar in both groups and did not predict the concomitant existence of adenomatous polyps. The male:female ratio was the same in both groups. The percent of detected polyps increased with age. A strong right shift in the location of the polyps was evident with increasing age. Multiple polyps were a common event in this Israeli population of symptomatic and high-risk asymptomatic patients. More than 30% of the polyps were found outside the reach of the sigmoidoscope, with this proportion increasing with age. These data provide further support to the claim that colonoscopy should therefore serve as the choice diagnostic tool in these high-risk populations.

Age Distribution↗

Tissue differences in fragile X mosaics: mosaicism in blood cells may differ greatly from skin.

The fragile X mutation is diagnosed from the structure of the FMR1 gene in blood cell DNA. An estimated 12 to 41% of affected males are mosaics who carry both a "full mutation" allele from which there is no gene expression and a "premutation" allele which has normal gene expression. We compared the DNA in blood cells and skin fibroblasts from four mosaic fragile X males to see if there was a difference in the relative amounts of premutation and full mutation alleles within the tissues of these individuals. Two of these males showed striking differences in the ratio of premutation to full mutation in different tissues while the other two showed only slight differences. These observations conform with the widely accepted hypothesis that the fragile X CGG repeat is unstable in somatic tissue during early embryogenesis. Accordingly, the mosaicism in brain and skin, which are both ectodermal in origin, may be similar to each other but different from blood which is not ectodermal in origin. Thus, the ratio of full mutation to premutation allele in skin fibroblasts might be a better indicator of psychological impairment than the ratio in blood cells.

Blood Cells↗

Immunocytochemistry and flow cytometry evaluation of human megakaryocytes in fresh samples and cultures of CD34+ cells.

Adhering platelets on the cell surface can give misleading results when doing flow cytometry analysis of platelet/megakaryocyte-specific glycoprotein (GP) antigens to enumerate megakaryocytes (MK) in mobilized peripheral blood (PB), apheresis products, or normal bone marrow (BM). For adequate quantification and characterization of human MK, we examined samples with parallel flow cytometry and immunocytochemistry. MK expression of GP IIb/IIIa (CD41a), GP Ib (CD42b), GP IIIa (CD61), CD45, CD33, and CD11b, and their light scatter properties were evaluated. Fresh samples of low density mononuclear cells (MNC) or purified CD34+ cells contained 10-45% of platelet-coated cells. Platelet-coated cells decreased dramatically after several days of incubation in a serum-free medium supplemented with stem cell factor, IL-3, IL-6, and/or GM-CSF. Between d 9-12, flow cytometry detected a distinct CD41a+ MK population, 8.3 +/- 1.3% in BM CD34 cell cultures (n = 7) and 13.1 +/- 2.1% in PB CD34 cell cultures (n = 14), comparable to immunocytochemistry data (7.8 +/- 1.9% and 16.4 +/- 2.6%, respectively). CD41a stained a higher proportion of MK than CD42b or CD61, while CD42b+ or CD61+ cells contained more morphologically mature MK than CD41a+ cells in cultures containing aplastic serum. When fluorescence emission of CD41a was plotted against forward-light scatter (FSC), subpopulations of small and large MK were observed. Such subpopulations overlapped in CD41a intensity and side-light scatter (SSC) property. Most MK co-expressed CD45 (98.8% positive) but not CD33 (80.7% negative) or CD11b (88.9% negative). Our data indicate that flow cytometry can be used effectively to identify MK. However, caution should be taken with samples containing adherent platelets.

Adult↗

Exercise myocardial perfusion SPECT in patients without known coronary artery disease: incremental prognostic value and use in risk stratification.

BACKGROUND: We evaluated the incremental prognostic value, the role in risk stratification, and the impact on patient management of myocardial perfusion single-photon emission computed tomography (SPECT) in a population of patients without prior myocardial infarction, catheterization, or revascularization. METHODS AND RESULTS: We examined 2200 consecutive patients who at the time of their dual-isotope SPECT had not undergone catheterization, coronary artery bypass surgery, or percutaneous transluminal coronary angioplasty and had no known history of previous myocardial infarction. Follow-up was performed at a mean of 566 +/- 142 days (97% complete) for hard events (cardiac death and myocardial infarction) and for referral to cardiac catheterization or revascularization within 60 days after nuclear testing. Examination of clinical, exercise, and nuclear models by use of pre-exercise tolerance test (ETT), post-ETT, and nuclear information using a stepwise Cox proportional hazards model and receiver-operating characteristic curve analysis revealed that nuclear testing added incremental prognostic value after inclusion of the most predictive clinical and exercise variables (global chi2 = 12 for clinical variables; 31 for clinical + exercise variables; 169 for nuclear variables; gain in chi2, P < .0001 for all; receiver-operating characteristic areas: 0.66 +/- 0.04 for clinical, 0.73 +/- 0.04 for clinical + exercise variables, 0.87 +/- 0.03 for nuclear variables, P = .03 for gain in area with exercise variables; P < .001 for increase with nuclear variables). Multiple logistic regression analysis revealed that scan information contributed 95% of the information regarding referral to catheterization with further additional information provided by presenting symptoms and exercise-induced ischemia. Referral rates to early catheterization and revascularization paralleled the hard event rates in all scan categories - very low referral rates in patients with normal scans and significant increases in referral rates as a function of worsening scan results. Even after stratification by clinical and exercise variables such as the Duke treadmill score, pre- and post-ETT likelihood of coronary artery disease, presenting symptoms, sex, and age, the nuclear scan results further risk-stratified the patient subgroups, thus demonstrating clinical incremental value. CONCLUSIONS: In a patient population with no evidence of previous coronary artery disease at overall low risk (1.8% hard event rate), myocardial perfusion SPECT adds incremental prognostic information and risk-stratifies patients even after clinical and exercise information is known. It appears that referring physicians use this test in an appropriate manner in selecting patients to be referred to catheterization or revascularization.

Cardiac Catheterization↗

Effect of low-power He-Ne laser on fracture healing in rats.

BACKGROUND AND OBJECTIVE: Helium-Neon (He-Ne) laser radiation has been found to accelerate fracture healing in laboratory animal models as well as in cultures of cells involved in this process. We investigated the radiological, biomechanical, and histological effects of He-Ne radiation on fracture healing in a rat model. STUDY DESIGN/MATERIALS AND METHODS: Sixty-two rats underwent bilateral open osteotomies of the tibiae followed by internal fixation with intramedullary wires. The right leg received He-Ne laser radiation of 0, 2, or 4 Joules every other day for 2 to 6 weeks while the left leg served as a control. RESULTS: Radiological and histological examinations of the osteotomy sites failed to show any enhancing effect of He-Ne laser radiation on the bone healing process. Biomechanically, the irradiated bones of two of the six test groups were significantly weaker than the controls. CONCLUSION: These results fail to support the previously reported enhancing effect of He-Ne laser radiation on fracture healing.

Animals↗

Thrombopoietin-stimulated ex vivo expansion of human bone marrow megakaryocytes.

The effect of thrombopoietin (TPO) on megakaryocytopoiesis (MKP) has been mainly studied using clonogenic assays in murine systems. In this study, we evaluated MKP in liquid culture using human bone marrow cells. While interleukin 3 (IL-3) and stem cell factor (SCF) are potent activators of TPO-stimulated MKP in the murine system, only IL-3 exhibited synergistic activity with TPO in cultures of human bone marrow. The IL-3 effect on TPO-stimulated megakaryocyte (MK) proliferation, expressed as the absolute number of MKs per seeded CD34+ cell, was more pronounced with purified CD34+ cell (8 +/- 1.6 SE versus 2.8 +/- 0.7 SE in the presence and absence of IL-3, respectively) than with mononuclear cells (MNC) (16 +/- 2.8 SE versus 11 +/- 2.0 SE). This effect of IL-3 on TPO-stimulated MK proliferation was due to a general proliferation of all cell types since the relative frequency of MKs (32.1 +/- 3 SE and 55.8 +/- 3 SE in MNC and CD34+ cells, respectively) was not affected by IL-3. The effect of TPO alone, TPO + IL-3, TPO + SCF, and TPO + IL-3 + SCF on MK proliferation was examined in MNC and CD34+ cultures. Greater numbers of MK per seeded CD34+ were observed in MNC compared to CD34+ cultures under all conditions except when TPO was added with both IL-3 and SCF. The enhancing effect of MNC was also observed on MK ploidy in the presence of TPO and IL-3. While proliferation and ploidy increase with TPO concentration in the murine system, they are inversely related in the human system. A significant 2.5-fold enhancement of TPO-induced MK proliferation was observed when purified CD34+ cells were cultured in inserts separated from human bone marrow stroma, indicating that soluble stimulatory factors are released from the stroma. These observations will be useful for ex vivo expansion of MKs to treat post-transplant or chemotherapy-associated thrombocytopenia.

Animals↗

Ovarian tumors in postmenopausal breast cancer patients treated with tamoxifen.

From September 1, 1989, to November 30, 1994, 175 menopausal breast cancer patients treated with tamoxifen were followed at the authors' institutions. During this period. 16 (9.1%) underwent total abdominal hysterectomy and bilateral salpingo-oophorectomy, for various indications. Of these, 10 (62.5%) had either uni- or bilateral ovarian tumors. The analysis of surgical findings showed an incidence of 5.7% (10/175) ovarian tumors among all the patients. In 2 (20%), the ovarian masses displayed enlargement over a relatively short period while on treatment. In 5 (50%) patients, the findings were bilateral. All tumors were detectable by ultrasonography, except four serous cystadenomas found in 3 women. The mean duration of tamoxifen treatment was 36.6 +/- 24.9 (range 9-86) months. The rate of 5.7% for ovarian tumors, in this selected group of patients, is four to five times higher than that reported for similar pathologic conditions detected by general screening with ultrasonographic scans among nonselected, asymptomatic, and untreated postmenopausal women. Two possibilities should be considered in the development of ovarian tumors coinciding with tamoxifen treatment; (1) women with breast malignancy are prone to develop benign or malignant ovarian tumors in relation to genetic factors, regardless of tamoxifen treatment; and (2) tamoxifen may stimulate enlargement of such tumors and may even cause them.

Aged↗

Trajectories and profiles of adaptive behavior in males with fragile X syndrome: multicenter studies.

We conducted two multicenter studies on adaptive trajectories and profiles in males with fragile X syndrome. Study 1 longitudinally assessed 29 males ages 1-20 years using age-equivalent scores from the Vineland Adaptive Behavior Scales. Fragile X boys ages 1-10 years showed significant gains in adaptive skills from first to second testing; males ages 11-20 years were stable in their adaptive development. Study 2 cross-sectionally examined 132 males ages 1-20 years. Significant age-related gains were found in boys ages 1-10, particularly in preschool children. Subjects ages 11-20 showed increased variability and nonsignificant relations between age and adaptive skills. Preliminary findings from 26 young adults with fragile X syndrome ages 21-40 years showed stable age-equivalent adaptive scores during these years. Relative strengths in daily living skills and weaknesses in communication were only evident among older subjects. Significant relations were found between adaptive behavior standard scores and IQ; these two scores also showed age-related declines that likely parallel one another. Findings are related to adaptive features in other genetic syndromes, and to directions for future adaptive behavior research.

Activities of Daily Living↗

Metastatic extraosseous Ewing tumor. Association of the additional translocation der(16)t(1;16) with the variant EWS/ERG rearrangement in a case of cytogenetically inconspicuous chromosome 22.

In Ewing sarcoma and related tumors, recently referred to as the Ewing tumors (ET), t(11;22)(q24q12) and its molecular genetic equivalent, the EWS/FLI-1 rearrangement, characterize approximately 85% of cases, while variant aberrations are rare. A second nonrandom aberration in ET is the unbalanced t(1;16) accompanying the t(11;22) in roughly 17% of cases. We present a 17-year-old man with estraosseous ET and multiple metastases, in whom the only cytogenetically detectable chromosomal aberration was der (16)t(1;16)(q12;q11.2). This finding was confirmed by fluorescence in situ hybridization (FISH). Using the RT-PCR technique, a variant EWS/ERG fusion transcript was noted, resulting from a t(21;22) chromosomal rearrangement which recently demonstrated in roughly 10% of ET. However, data on possible biologic differences in EWS/FLI-1 versus EWS/ERG expressing ET are as yet unavailable. This is the first reported combination of t(1;16) with the EWS/ERG rearrangement. A possible significance of this finding for Ewing tumor progression is discussed.

Adolescent↗

Diagnostic value of transvaginal color Doppler flow in ovarian torsion.

OBJECTIVE: To evaluate the role of Doppler flow in the diagnostic process of ovarian torsion. METHODS: Twenty-two patients who displayed the clinical symptoms of abdominal pain concomitant with an ovarian mass and were scheduled for explorative laparoscopy were enrolled in the study. The cohort was divided into 3 groups: (A) 8 patients with clinical and sonographic evidence of torsion; (B) 8 patients with abdominal pain and sonographic diagnosis of hemorrhagic cyst; and (C) 6 patients with a simple cystic mass who had undergone explorative surgery due to abdominal pain. RESULTS: After Doppler flow imaging, Group A displayed no blood flow within the mass, and surgery confirmed the diagnosis of ovarian torsion. Seven of the 8 group B patients showed ovarian vascular flow (RI = 0.472 +/- 0.067). Only 2 of the 6 Group C patients displayed vascular flow (RI = 0.680 +/- 0.129) within an untwisted cyst, confirmed by laparoscopy. CONCLUSIONS: The combination of Doppler flow imaging with the morphologic assessment improves the diagnostic accuracy of ovarian torsion.

Abdominal Pain↗

Effective risk stratification using exercise myocardial perfusion SPECT in women: gender-related differences in prognostic nuclear testing.

OBJECTIVES: This study was designed to evaluate the incremental prognostic value over clinical and exercise variables of rest thallium-201/exercise technetium-99m sestamibi single-photon emission computed tomography (SPECT) in women compared with men and to determine whether this test can be used to effectively risk stratify patients of both genders. BACKGROUND: To minimize the previously described gender-related bias in the evaluation of coronary artery disease in women, there is a need to identify a noninvasive testing strategy that is able to accurately and effectively risk stratify women. METHODS: We identified 4,136 consecutive patients (2,742 men, 1,394 women) who underwent dual-isotope SPECT. The incremental value of nuclear testing was determined using both a stepwise Cox proportional hazards model and Kaplan-Meier survival analysis. Receiver operating characteristic curve analysis was performed to determine test discrimination for high risk patients in men and women. RESULTS: The patient population was followed up for 20 +/- 5 months for events (cardiac death or nonfatal myocardial infarction). During this time, 63 myocardial infarctions and 32 cardiac deaths occurred in the men, and 31 myocardial infarctions and 14 cardiac deaths occurred in the women. Nuclear testing significantly stratified both men and women irrespective of their rest electrocardiogram. Cox proportional hazards analysis revealed that nuclear testing added incremental prognostic value in both men and women after inclusion of the most predictive clinical exercise variables (overall chi-square 89 in men vs. 120 in women, p < 0.005). Kaplan-Meier survival analysis demonstrated that nuclear testing further stratified men and women with both intermediate to high and low prescan likelihoods of coronary artery disease (p < 0.005 for all). Receiver operating characteristic curve analysis demonstrated superior discrimination for the nuclear scan results in identifying high risk women than men (area under the curve: 0.84 +/- 0.03 vs 0.71 +/- 0.03 in men, p < 0005). The odds ratio comparing event rates in patients with women than in men, suggesting superior stratification using nuclear testing in women. CONCLUSIONS: Dual-isotope myocardial perfusion imaging yields incremental prognostic value in both men and women. This modality identifies low risk women and men equally well but relatively high risk women more accurately than relatively high risk men and, thus, is able to stratify women more effectively than men.

Bias↗

Impact of myocardial perfusion single-photon emission computed tomography on referral to catheterization of the very elderly. Is there evidence of gender-related referral bias?

OBJECTIVES: This study sought to assess the impact of myocardial perfusion studies on subsequent management in the very elderly with respect to referral to catheterization or revascularization. BACKGROUND: The very elderly are a rapidly growing segment of the U.S. population, and myocardial perfusion studies are frequently performed in this patient subset for evaluation of coronary artery disease. METHODS: The study utilized 1,006 consecutive patients > or = 80 years old (511 men, 495 women) who underwent stress myocardial perfusion single-photon emission computed tomography (SPECT) using pharmacologic stress (n = 605) or treadmill exercise (n = 401). Referral to catheterization or revascularization within 60 days of the nuclear scan was correlated with clinical and nuclear variables. RESULTS: Catheterization and revascularization were performed in 119 and 77 patients, respectively. Stratification of referral rates showed a low rate in normal and mildly abnormal scan categories and significantly higher rates in patients with severely abnormal scan results irrespective of the presenting symptoms or pretest likelihood of coronary artery disease. Multiple logistic regression analysis of clinical and nuclear variables revealed that extent and severity of reversibility by SPECT and the final scan result were the two most powerful predictors of referral to catheterization and revascularization in men and women (catheterization: chi-square 65 and 78; revascularization: chi-square 37 and 68, respectively). Overall, referral rates to catheterization and revascularization were similar in men and women (catheterization: 13% vs. 11%; revascularization: 8% vs. 8%, respectively). However, women with severely abnormal scan results were more frequently referred to catheterization (28% vs. 18%, p < 0.03) and revascularization (21% vs. 12%, p < 0.01) than men. CONCLUSIONS: In patients > or = 80 years old, myocardial perfusion SPECT had a significant impact on patient management. The apparent discrepancy in referral rates for interventional management in men and women is unexplained but may be appropriate in light of our previous observations that women with severely abnormal scan results are at increased risk for hard cardiac events than are men with severely abnormal scan results.

Age Factors↗

Common endometrial decidual reaction in postmenopausal breast cancer patients treated with tamoxifen and progestogens.

In order to assess endometrial reaction to the combined treatment of tamoxifen and progestogens in asymptomatic postmenopausal breast cancer patients, we evaluated all such patients by vaginal ultrasonography and by histological examination of endometrial samplings. All patients were initially treated with tamoxifen, and progestogens were then added when metastases became evident. Of 12 patients included in the study, eight (66.66%) showed evidence of strong endometrial stromal decidualization, while three (25%) had decidual reactions in endometrial polyps. Overall, 11 (91.66%) of the patients had decidual reactions, and all were treated with progestogens for > or = 3 consecutive months. One patient, treated with progestogens for 1 months, had an inactive endometrium. All but three had thickened endometria (> 10 mm) on ultrasonographic evaluation. These data show that postmenopausal breast cancer patients who received progestogens for < or = 3 months, and who concomitantly took tamoxifen, had a uniform decidual reaction in all uteri.

Adult↗

Time-dependent effect of tamoxifen therapy on endometrial pathology in asymptomatic postmenopausal breast cancer patients.

Various endometrial lesions were more frequent among asymptomatic postmenopausal breast cancer patients who were treated with tamoxifen for > 48 consecutive months (30.8%) when compared with similar patients who were treated for 6-24 months or for 25-48 months (20.8% and 12.5%, respectively). However, this difference was not statistically significant. There were also no significant differences in the frequency of the various endometrial lesions between these three groups, although endometrial polyps were more frequently found among those treated for > 48 months. Overall, 20.7% of the 164 tamoxifen-treated patients in the study had an endometrial pathology. It can be concluded that there is a slight tendency among those postmenopausal patients who have been treated for > 48 consecutive months to have a higher frequency of endometrial lesions.

Analysis of Variance↗