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Biomedical subjects

D Kleinman

Publications and source records attributed to D Kleinman.

At least 19 recordsLinked to original sources
PubMed2001

High altitude retinal hemorrhages in a Colorado skier.

High altitude retinal hemorrhages are commonly seen at altitudes above 4270 m. While these hemorrhages are generally asymptomatic, macular involvement may result in permanent visual acuity deficit. We present the case of a 29-year-old male recreational skier who traveled to a ski resort at 2930 m, ascended to 3470 m, and developed acute mountain sickness, high altitude pulmonary edema, and bilateral retinal hemorrhages. A funduscopic examination to determine if macular retinal hemorrhage is present may be performed by clinicians in the final assessment of patients following altitude illness.

Adult↗
PubMed2000

Fewer women than men have positive SPECT and PET cardiac findings among patients with no history of heart disease.

UNLABELLED: A lower detection rate of coronary artery disease (CAD) has been reported for SPECT imaging in women, despite the fact that similar numbers of women and men die each year of heart disease. Ruling out instrumentation as a possible source of this low detection rate for CAD in women could be important in determining the root cause of this difference. METHODS: Patients were referred by cardiologists and randomized to PET or SPECT by the imaging center. A total of 210 patients (106 women, 104 men) were enrolled in this study, with 105 imaged by dual-isotope SPECT and 105 imaged by 82Rb PET. Rest/stress scanning was performed using dipyridamole. The effects of sex, prior history of CAD, and instrumentation on the detection of positive scans were determined using multiple logistic regression analysis with positive scans as the endpoint. RESULTS: For the total study population, sex and prior history of CAD are significantly associated with positive scans, whereas imaging modality and age are not. There was no significant interaction between sex and prior history of CAD. Men have 4.1-fold greater odds of having a positive nuclear scan than women, and patients with prior history of CAD have 5.2-fold greater odds of a positive scan after controlling for the confounding effects of age and imaging modality. In the subgroup of patients with no prior history of heart disease, men have 3.9-fold greater odds of a positive scan than women, and the odds ratio of a positive scan is 2.5-fold greater for PET than for SPECT. There was no statistical difference in the number of positive scans by SPECT or PET, or positive scans by sex in patients with documented history of CAD. CONCLUSION: Fewer women than men have positive nuclear cardiology scans by both PET and SPECT, despite similar symptoms. Instrumentation characteristics alone do not account for this sex-based difference and suggest the possibility that early CAD may present differently in women than in men.

Aged↗
PubMed1998

Magnetic electroanatomical mapping for ablation of focal atrial tachycardias.

Uniform success for ablation of focal atrial tachycardias has been difficult to achieve using standard catheter mapping and ablation techniques. In addition, our understanding of the complex relationship between atrial anatomy, electrophysiology, and surface ECG P wave morphology remains primitive. The magnetic electroanatomical mapping and display system (CARTO) offers an on-line display of electrical activation and/or signal amplitude related to the anatomical location of the recorded sites in the mapped chamber. A window of electrical interest is established based on signals timed from an electrical reference that usually represents a fixed electrogram recording from the coronary sinus or the atrial appendage. This window of electrical interest is established to include atrial activation prior to the onset of the P wave activity associated with the site of origin of a focal atrial tachycardia. Anatomical and electrical landmarks are defined with limited fluoroscopic imaging support and more detailed global chamber and more focal atrial mapping can be performed with minimal fluoroscopic guidance. A three-dimensional color map representing atrial activation or voltage amplitude at the magnetically defined anatomical sites is displayed with on-line data acquisition. This display can be manipulated to facilitate viewing from any angle. Altering the zoom control, triangle fill threshold, clipping plane, or color range can all enhance the display of a more focal area of interest. We documented the feasibility of using this single mapping catheter technique for localizing and ablating focal atrial tachycardias. In a consecutive series of 8 patients with 9 focal atrial tachycardias, the use of the single catheter CARTO mapping system was associated with ablation success in all but one patient who had a left atrial tachycardia localized to the medial aspect of the orifice of the left atrial appendage. Only low power energy delivery was used in this patient because of the unavailability of temperature monitoring in the early version of the Navistar catheter, the location of the arrhythmia, and the history of arrhythmia control with flecainide. No attempt was made to limit fluoroscopy time in our study population. Nevertheless, despite data acquisition from 120-320 anatomically distinct sites during global and more detailed focal atrial mapping, total fluoroscopy exposure was typically < 30 minutes and was as little as 12 minutes. The detailed display capabilities of the CARTO system appear to offer the potential of enhancing our understanding of atrial anatomy, atrial activation, and their relationship to surface ECG P wave morphology during focal atrial tachycardias.

Catheter Ablation↗
PubMed1996

Successful catheter ablation of an inferoseptal accessory pathway within the coronary sinus in a patient with a previously unsuccessful attempt at surgical interruption. Coronary sinus ablation for Wolff-Parkinson-White syndrome.

In a patient with Wolff-Parkinson-White syndrome and a right inferoseptal accessory pathway who had had a previously unsuccessful surgical attempt at accessory pathway ablation, the accessory pathway was found to be adjacent to a branch of the coronary sinus. Radiofrequency energy was delivered within this branch to ablate the pathway successfully. This demonstrates an alternative approach to the more common method of radiofrequency ablation of accessory pathways from a tricuspid or mitral annular location.

Adult↗
PubMed1996

Stimulation of endometrial cancer cell growth by tamoxifen is associated with increased insulin-like growth factor (IGF)-I induced tyrosine phosphorylation and reduction in IGF binding proteins.

A significant increase in endometrial cancer incidence in tamoxifen-treated breast cancer patients has been reported in many recent studies. The major growth stimulators of endometrial tumors are estrogens, but paradoxically, tamoxifen, a known antiestrogen, also stimulates their growth. The mode of action of estrogen can be partially explained by the modulation of insulin-like growth factor (IGF) autocrine or paracrine action. The purpose of the present study was to examine the involvement of the IGF system in the tamoxifen-stimulated growth of Ishikawa endometrial cancer cells by quantitating the IGF-I receptors and their phosphorylation, as well as membrane associated and secreted IGF-binding proteins (IGFBPs). Tamoxifen did not affect the number or affinity of IGF-I receptors. On the other hand, tamoxifen, similar to estradiol, increased IGF-I-stimulated tyrosine phosphorylation of cellular substrates. In contrast, in MCF-7 mammary cancer cells, tamoxifen reduced IGF-induced tyrosine phosphorylation in the presence of estradiol. The pure antiestrogen LY156758 did not affect Ishikawa basal cell growth but inhibited estradiol- and tamoxifen-induced growth. Growth inhibition by LY156758 of tamoxifen and estradiol-stimulated cells was accompanied by a corresponding inhibition of IGF-stimulated tyrosine phosphorylation. Tamoxifen caused a 3-fold decrease in membrane-associated IGFBPs. Moreover, a reduction in soluble IGFBPs was also observed, making the IGF peptides more available to the receptors. A parallel decrease in IGFBP-3 mRNA was also detected. These experiments suggest that tamoxifen, like estradiol, directly sensitizes endometrial cancer cells to the effects of IGFs that act through the type I receptor. Furthermore, the decrease in IGFBPs and the increase in tyrosine phosphorylation in the presence of tamoxifen provides a molecular mechanism that accounts for the uterotropic effects that are seen with tamoxifen therapy.

Antineoplastic Agents, Hormonal↗
PubMed1995

Components of the IGF system mediate the opposing effects of tamoxifen on endometrial and breast cancer cell growth.

The involvement of the IGF system in the growth regulation of hormone-dependent (e.g. endometrial and breast) cancer cells was studied. We chose two opposing effects of tamoxifen: the paradoxical stimulation of Ishikawa endometrial cancer cells growth and its inhibitory effect on MCF-7 mammary cancer cells. The results clearly confirm our working hypothesis that the IGF system is involved in growth regulation of these cancer cells irrespective of the direction of the drug effect. The following parameters of the IGFs system were studied: IGF-I receptors, IGF-I stimulated protein tyrosine phosphorylation, and membrane-associated and secreted IGF-binding proteins (IGFBPs). In Ishikawa cells, tamoxifen, similar to estradiol, increased IGF-I stimulated tyrosine phosphorylation of cellular substrates in accordance with its effect on cell growth. This effect of tamoxifen was inverted in MCF-7 cells. Tamoxifen did not affect the number or affinity of IGF-I receptors in both Ishikawa and MCF-7 cells, however, it caused a three-fold decrease in membrane-associated IGFBPs in the endometrial cells but an increase in these proteins in breast cancer cells. Similar but much less pronounced changes in soluble IGFBPs were observed. Our results indicate that the opposing growth effects of tamoxifen an endometrial and mammary cancer cells are associated with modulation of the IGF system components, mainly with reciprocal changes in membrane-associated IGFBPs.

Breast Neoplasms↗
PubMed1995

Modulation of insulin-like growth factor I (IGF-I) receptors and membrane-associated IGF-binding proteins in endometrial cancer cells by estradiol.

Insulin-like growth factor I (IGF-I) receptors and membrane-associated IGF-binding proteins (IGFBPs) were examined in Ishikawa endometrial cancer cells. Our findings suggest that about 95% of [125I]IGF-I is bound to membrane-associated IGFBPs rather than to IGF-I receptors. Specifically, [125I]IGF-I binding to cell membranes could be completely displaced by cold IGF-I or IGF-II, but not by insulin, suggesting that binding was primarily due to IGFBPs. This was confirmed by using [125I]des-(1-3)IGF-I as the ligand. Des-(1-3) IGF-I binds with high affinity to IGF-I receptors, but with markedly lower affinity to IGFBPs. [125I]Des-(1-3)IGF-I bound to Ishikawa cells was displaced by IGF-I, IGF-II, and insulin. These results suggest that measuring IGF-I receptor levels using labeled IGF-I may be misleading. Accordingly, we evaluated the differential binding of [125I]IGF-I and [125I]des-(1-3)IGF-I to study the involvement of the IGF system in the stimulation of Ishikawa cell growth by estradiol. IGF-I stimulates Ishikawa cell proliferation, but at low concentrations, and this stimulation is largely dependent on the presence of estradiol. Estradiol caused a 2.5-fold increase in IGF-I receptor levels. Moreover, estradiol reduced soluble IGFBP levels, presumably increasing the availability of IGFs for their receptors. This elevation in IGF-I receptor levels and the decrease in IGFBP levels were accompanied by a 3.5-fold increase in IGF-I receptor messenger RNA and a 2.5-fold decrease in IGFBP messenger RNAs. These experiments suggest that estradiol sensitizes endometrial cancer cells to the effects of IGFs by simultaneously elevating receptor levels and decreasing (potentially inhibitory) IGFBP levels.

Binding, Competitive↗
PubMed1994

Direct growth inhibition of human endometrial cancer cells by the gonadotropin-releasing hormone antagonist SB-75: role of apoptosis.

OBJECTIVE: Our objective was to study the direct action of the gonadotropin-releasing hormone antagonist SB-75 and the agonist buserelin on the proliferation of endometrial cancer cells. STUDY DESIGN: Two human endometrial cell lines that differ in histologic subtype and estrogen receptor content were treated with gonadotropin-releasing hormone analog. We measured the number of viable cells, cell cycle parameters, and apoptotic processes. RESULTS: Growth of the Ishikawa cells was inhibited by SB-75 in a dose-dependent manner. 17 beta-Estradiol partially abolished the inhibitory effect of SB-75. The growth of the HEC-1A cells was not affected by the antagonist. Neither endometrial cancer cell line showed significant sensitivity to the agonist buserelin. Tenfold concentration of the gonadotropin-releasing hormone agonist did not abolish the inhibitory effect of the antagonist on cell growth. The growth inhibition was not associated with any change in cell cycle parameters but was associated with an induction of apoptosis. CONCLUSION: The gonadotropin-releasing hormone antagonist SB-75 directly inhibits the growth of some human endometrial cancer cells and thus may be suitable for the treatment of endometrial tumors.

Adenocarcinoma, Papillary↗
PubMed1993

Regulation of endometrial cancer cell growth by insulin-like growth factors and the luteinizing hormone-releasing hormone antagonist SB-75.

The involvement of IGFs in growth regulation of the Ishikawa endometrial tumor cell line and the possible interference of LH-RH analogues with a potential autocrine or paracrine loop involving IGFs was evaluated. The mitogenic effects of IGF-I, IGF-II, and insulin were compared. IGF-I was found to be 3-fold more potent than IGF-II and 30-fold more potent than insulin, suggesting that the effects of these growth factors are mediated by the IGF-I receptor. Ishikawa endometrial cancer cells secrete IGF-II, but not IGF-I, and insulin (1 microM) stimulates IGF-II release. The LH-RH antagonist [Ac-D-Nal(2)1, D-Phe(4Cl)2, D-Pal(3)3, D-Cit6, D-Ala10]-GnRH (SB-75, CETRORELIX) inhibited basal and IGF-induced growth. Moreover, this antagonist almost completely inhibited IGF-II release from Ishikawa cells, while having no significant effect on the number or affinity of IGF-I binding sites. Inhibition of IGF-II release occurred at a lower SB-75 concentration than that needed for a reduction in cell number. The ED50 of SB-75 for IGF-II release was 0.3 microM as compared to 1.5 microns concentration which is required for reduction in cell number, suggesting that inhibition of growth factor release precedes cell growth inhibition. We conclude that the LH-RH antagonist SB-75 can inhibit the growth of endometrial cancer cells by interfering with the autocrine action of IGF-II and also by directly inhibiting the growth-stimulatory effects of IGFs, probably through effects on a post-receptor mechanism.

Cell Division↗
PubMed1990

The use of heuristic strategies in the interpretation of pronouns.

The aim of the two experiments reported here was to distinguish between two heuristic strategies that have been proposed to account for the assignment of pronouns: the subject assignment strategy and the parallel function strategy. According to the subject assignment strategy, a pronoun is assigned to a preceding subject noun phrase, whereas according to the parallel function strategy, a pronoun is assigned to a previous noun phrase in the same grammatical position as the pronoun. These two strategies were tested by examining the interpretation of single object pronouns, first in a reading task and second in an assignment task. In both experiments, there was a strong preference for assigning an object pronoun to the preceding subject noun phrase, thus supporting the subject assignment strategy. However, this was only the case for pronouns that were linguistically ambiguous. When assignment was constrained by gender, there was no effect of either strategy. It is suggested that heuristic strategies are only used in the absence of other strong cues to assignment.

Attention↗
PubMed1990

Role of midcycle FSH surge in follicular development.

The present study was undertaken to examine the importance of the proestrous surge of FSH for follicular development during the following cycles in the rat. The midcycle FSH surges were blocked in several consecutive cycles (1-5) by injecting proestrous rats with pentobarbital. The rats were sacrificed on the day of proestrus following the appropriate number of blocked FSH surges and their ovaries were removed for either direct measurements or for histological workout. The number and diameter of follicles were determined in the excised ovaries. Two or three cycles of barbiturate treatment reduced the number and diameter of the follicles. No large follicles (greater than 0.4 mm) were observed in the ovaries of rats in which four or five gonadotropin surges were blocked. A repeat experiment with concomitant supplementary hCG administration yielded the same results. Addition of exogenous FSH canceled the effect of pentobarbital. The cohort observed on ovaries after four cycles of treatment with pentobarbital and FSH resembled that observed in control rats. Histological measurements supported the results obtained with fresh ovaries. It is therefore suggested that in the third cycle preceding the ovulatory one, the midcycle FSH surge determines which follicles will be able to adequately develop in the following three cycles. In the cycle preceding the ovulatory one, the midcycle FSH peak 'rescues' a group of follicles and prepares them for a proper response to the FSH elevation taking place at the beginning of the subsequent ovulatory cycle. This process allows the selection of the dominant follicles which will respond by ovulation to the ensuing LH peak.

Animals↗
PubMed1989

Inhibition of Chlamydia trachomatis growth in endometrial cells by copper: possible relevance for the use of the copper IUD.

There is agreement that the relative risk of developing pelvic inflammatory disease (PID) increases among women who use the intrauterine contraceptive device (IUD). The role of Chlamydia in causing PID among IUD users is not clear. The present study demonstrates that Chlamydia trachomatis growth can be inhibited in cultured human endometrial cells by copper ions at concentrations known to be released by the copper IUDs. More than 98% inhibition was produced with 10(-5) and 10(-6) M of copper. Both C. trachomatis serovar E and a lymphogranuloma venereum Chlamydia serovar L2 (LGV) were inhibited by the copper ions. Although the mechanism of the inhibition is not known, the continuous presence of the copper ions during and after adherence appeared to be necessary for maximal effect. If such inhibition occurs in vivo, it is possible that copper ions released from the copper-containing IUD may partially protect against chlamydial infection.

Cells, Cultured↗
PubMed1989

Thromboembolization complicating left ventricular pseudoaneurysm: serial two-dimensional and color-flow Doppler echocardiographic observations.

A left ventricular pseudoaneurysm was diagnosed by two-dimensional echocardiography and color-flow Doppler imaging, and confirmed by computerized tomography and angiocardiography, in a man with known coronary disease who had had recent recurrent systemic emboli. A thrombus within the pseudoaneurysm was visualized, and its disappearance on serial echocardiograms coincided with the occurrence of embolization to the aortic bifurcation.

Aged↗
PubMed1988

Results of in vitro fertilization in women with antisperm antibodies in serum, cervical mucus, and follicular fluid.

This study was undertaken to investigate the presence of antisperm antibodies (ASA) in serum, cervical mucus, and follicular fluid (FF) of women undergoing in vitro fertilization and embryo transfer (IVF-ET). IgG and IgA ASA directed mostly against sperm head were found at similar concentrations in serum, cervical mucus, and FF of 2 of 34 patients. Ninety-one percent fertilization and 100% cleavage rates, respectively, were observed in one of the two patients. No fertilization occurred in the second patient. In both women, in vitro sperm penetration tests revealed hostile mucus and repeated postcoital tests were poor. It is concluded that the sperm-cervical mucus penetration test and mucus ASA measurements are useful in establishing the diagnosis of immunological infertility.

Adult↗
PubMed1987

Acid phosphatase levels in follicular fluids following induction of ovulation in in vitro fertilization patients.

Considerable evidence indicates that changes in acid phosphatase (AP) activity at the ovarian level play a role in the process of ovulation. In this study the concentrations of AP were determined in follicular fluids collected from follicles of 52 women at the time of laparoscopy performed in connection with an in vitro fertilization program. In each of the 52 women at least one ovum was harvested. Of the 52 ova, 28 cleaved in vitro, while in 24 ova cleavage was not seen. Levels of AP in follicular fluids of women whose ova did not cleave were significantly lower than those found in follicular fluids of women with at least one ovum undergoing cleavage: 0.45 +/- 0.14 (SE) and 4.78 +/- 0.37 Bess Lowry Units (BLU), respectively. Comparison of AP levels in follicular fluids of women who conceived (5) and women whose ova cleaved, but in whom pregnancy was not achieved (23), did not reveal significant differences: 5.87 +/- 1.29 and 4.55 +/- 0.35 BLU, respectively. Moreover, the enzyme level was typical for a woman and not for a follicle. Fluids of two different follicles of the same woman, when one ovum cleaved and one did not, showed similar AP levels. AP levels were high in all samples follicles of women in whom at least one ovum cleaved. These findings indicate that the presence of certain levels of acid phosphatase represents an important, albeit not the sole, condition for ovum maturation. Moreover, the follicular fluid levels of AP could serve as an indicator of proper timing of the follicular puncture in relation to the human chorionic gonadotropin injection (or the luteinizing hormone peak).

Acid Phosphatase↗
PubMed1987

The effects of contraceptive hormones on the replication of Chlamydia trachomatis in human endometrial cells.

Several recent reports have documented a lower incidence of pelvic inflammatory disease (PID) among oral contraceptive users. The interpretation of this observation is difficult because the action of the contraceptive hormones may be directly by action on a specific host cell-parasite relationship, or indirectly via their action on other systems. In the present study we investigated the susceptibility of cultured human epithelial cells of the endometrium to infection by chlamydia and the influence of contraceptive steroids (ethinyl estradiol, mestranol and medroxyprogesterone acetate) upon replication of chlamydia in these cells. Forty-eight hours post-infection, elementary and reticulate bodies were observed in vacuoles of the infected endometrial cells by electron microscopy. Treatment of chlamydial-infected cells with contraceptive steroids in three different concentrations (10(-5)M, 10(-6)M and 10(-7)M) resulted in no effect on chlamydial replication, as examined by one-step growth curve. These results indicate that contraceptive hormones do not prevent chlamydial infection by direct effect on the replication of the agent.

Chlamydia Infections↗