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Biomedical subjects

N Freedman

Publications and source records attributed to N Freedman.

At least 19 recordsLinked to original sources

Cerebral activation associated with sexual arousal in response to a pornographic clip: A 15O-H2O PET study in heterosexual men.

This study attempted to use PET and 15O-H2O to measure changes in regional cerebral blood flow (rCBF) during sexual arousal evoked in 10 young heterosexual males while they watched a pornographic video clip, featuring heterosexual intercourse. This condition was compared with other mental setups evoked by noisy, nature, and talkshow audiovisual clips. Immediately after each clip, the participants answered three questions pertaining to what extent they thought about sex, felt aroused, and sensed an erection. They scored their answers using a 1 to 10 scale. SPM was used for data analysis. Sexual arousal was mainly associated with activation of bilateral, predominantly right, inferoposterior extrastriate cortices, of the right inferolateral prefrontal cortex and of the midbrain. The significance of those findings is discussed in the light of current theories concerning selective attention, "mind reading" and mirroring, reinforcement of pleasurable stimuli, and penile erection.

Adult↗

Size-dependent DNA mobility in cytoplasm and nucleus.

The diffusion of DNA in cytoplasm is thought to be an important determinant of the efficacy of gene delivery and antisense therapy. We have measured the translational diffusion of fluorescein-labeled double-stranded DNA fragments (in base pairs (bp): 21, 100, 250, 500, 1000, 2000, 3000, 6000) after microinjection into cytoplasm and nucleus of HeLa cells. Diffusion was measured by spot photobleaching using a focused argon laser spot (488 nm). In aqueous solutions, diffusion coefficients of the DNA fragments in water (D(w)) decreased from 53 x 10(-8) to 0.81 x 10(-8) cm(2)/s for sizes of 21-6000 bp; D(w) was related empirically to DNA size: D(w) = 4.9 x 10(-6) cm(2)/s.[bp size](-0.72). DNA diffusion coefficients in cytoplasm (D(cyto)) were lower than D(w) and depended strongly on DNA size. D(cyto)/D(w) decreased from 0.19 for a 100-bp DNA fragment to 0.06 for a 250-bp DNA fragment and was <0.01 for >2000 bp. Diffusion of microinjected fluorescein isothiocyanate (FITC) dextrans was faster than that of comparably sized DNA fragments of 250 bp and greater. In nucleus, all DNA fragments were nearly immobile, whereas FITC dextrans of molecular size up to 580 kDa were fully mobile. These results suggest that the highly restricted diffusion of DNA fragments in nucleoplasm results from extensive binding to immobile obstacles and that the decreased lateral mobility of DNAs >250 bp in cytoplasm is because of molecular crowding. The diffusion of DNA in cytoplasm may thus be an important rate-limiting barrier in gene delivery utilizing non-viral vectors.

Cell Nucleus↗

SPECT attenuation artifacts in normal and overweight persons: insights from a retrospective comparison of Rb-82 positron emission tomography and TI-201 SPECT myocardial perfusion imaging.

PURPOSE: Myocardial perfusion imaging can be performed using SPECT or positron emission tomography (PET). SPECT has lower specificity than PET, largely as a result of attenuation artifacts; however, it is more widely available. The authors describe a study of the effect of sex and body weight on the incidence of SPECT attenuation artifacts using a retrospective comparison of TI-201 SPECT and Rb PET. METHODS: One hundred sixty-one persons (101 men, 60 women; 81 normal weight, 80 overweight) underwent TI-201 SPECT and Rb PET. The incidence of observed perfusion defects was studied in territories of the three major coronary arteries. SPECT and PET results were also compared with those of angiography in a subset of 75 patients. RESULTS: One hundred fourteen defects were reported on Rb PET compared with 176 defects with TI-201 SPECT. Excess TI-201 SPECT defects occurred in male and female, normal-weight and overweight persons. The average specificity was 64% for TI-201 SPECT and 84% for Rb PET, reflecting this difference. CONCLUSIONS: Attenuation artifacts in TI-201 SPECT occur frequently and are not confined to easily identifiable subgroups of patients. Therefore, measures to improve specificity of SPECT (e.g., prone or gated imaging) or alternative imaging techniques such as PET have potential advantages for everyone, not simply for obese patients and women with large breasts. In addition, awareness of the prevalence of SPECT attenuation artifacts, in both sexes and all weight categories, may contribute to improved accuracy of interpretation.

Artifacts↗

Contribution of whole body F-18-FDG-PET and lymphoscintigraphy to the assessment of regional and distant metastases in cutaneous malignant melanoma. A pilot study.

AIM: This pilot study describes use of whole body PET (WB PET) for staging of melanoma. WB PET in conjunction with lymphoscintigraphy (LS) for evaluating status of the sentinel lymph node (SLN) in primary melanoma was investigated with comparison to histopathological results. WB PET was also used both for primary and metastatic melanoma for screening for distant metastases, restaging and follow-up. METHODS: Group I: 17 patients with primary cutaneous melanoma underwent LS, WB PET and SLN dissection. WB PET findings were compared with biopsy results at the SLN site and were used for screening for distant metastases. Group II: 17 patients with a history of melanoma underwent WB PET for follow-up and/or restaging. Results were confirmed or refuted by other radiological modalities or by biopsy or clinical follow-up. RESULTS: Group I: out of 20 SLNs identified by LS in the 17 patients, 18 were negative on WB PET and 2 were positive. 19/20 WB PET findings were confirmed either by histopathology or by clinical follow-up (20 mo). Accuracy was 94% for the assessment of the status of the SLN. Group II: WB PET findings altered staging and treatment in 12/17 patients and confirmed the validity of treatment in 3/17 patients. Overall, in 15/17 patients (88%), WB PET had an impact on treatment strategy. CONCLUSION: Further studies are required to demonstrate if WB PET can become a reliable non-invasive alternative to surgery in the characterization of the SLN. WB PET is important as a baseline in primary localized melanoma and decisively impacts patient management in metastatic melanoma.

Adult↗

The effectiveness of psychoanalytic psychotherapy: the role of treatment duration, frequency of sessions, and the therapeutic relationship.

This is an effectiveness study of treatment outcome that relies on patients' perception of their mental health during and after psychoanalytic psychotherapy. Ninety-nine outpatients attending the IPTAR Clinical Center (ICC) responded to the Effectiveness Questionnaire (EQ) adapted from that developed by Consumer Reports. Effectiveness is studied from various perspectives. Findings indicated (1) an incremental gain in effectiveness scores from six to over twenty-four months of therapy; (2) an incremental gain with greater session frequency from one to two or three weekly sessions; (3) facilitation of effectiveness by the experience of a positive relationship with the therapist; (4) an interplay between clinical syndrome and treatment conditions. A method giving clinical validity to the quantitative findings is described. Brief summaries of two recorded interviews reveal differential reconstruction of events that had occurred during treatment. The findings are discussed from the vantage point of two hypotheses: cognitive dissonance and internalization of therapeutic experience.

Adult↗

Matrix metalloproteinase stromelysin-1 triggers a cascade of molecular alterations that leads to stable epithelial-to-mesenchymal conversion and a premalignant phenotype in mammary epithelial cells.

Matrix metalloproteinases (MMPs) regulate ductal morphogenesis, apoptosis, and neoplastic progression in mammary epithelial cells. To elucidate the direct effects of MMPs on mammary epithelium, we generated functionally normal cells expressing an inducible autoactivating stromelysin-1 (SL-1) transgene. Induction of SL-1 expression resulted in cleavage of E-cadherin, and triggered progressive phenotypic conversion characterized by disappearance of E-cadherin and catenins from cell-cell contacts, downregulation of cytokeratins, upregulation of vimentin, induction of keratinocyte growth factor expression and activation, and upregulation of endogenous MMPs. Cells expressing SL-1 were unable to undergo lactogenic differentiation and became invasive. Once initiated, this phenotypic conversion was essentially stable, and progressed even in the absence of continued SL-1 expression. These observations demonstrate that inappropriate expression of SL-1 initiates a cascade of events that may represent a coordinated program leading to loss of the differentiated epithelial phenotype and gain of some characteristics of tumor cells. Our data provide novel insights into how MMPs function in development and neoplastic conversion.

Animals↗

On receiving the patient's transference: the symbolizing and desymbolizing countertransference.

This is an empirical study of the therapist's experience of the patient delineating the boundaries between empathy and constructive and destructive forms of countertransference. The unique step was taken of focusing a video camera on the therapist in order to trace the therapist's nonverbal behavior during listening. The same therapist was observed first in a "not-so-difficult" and then a "difficult" session; the sessions could then be distinguished along dimensions of rhythmicity or arrhythmicity of nonverbal behavior. These observations suggested three modes of experiencing the patient: empathy marked by rhythmicity, a symbolizing countertransference marked by a transitory arrhythmicity, and a desymbolizing countertransference marked by continuous arrhythmicity. The congruence of these formulations based on direct observation of therapist behavior and ones derived from retrospective reconstructions of analysts in sessions (Schwaber, Jacobs, and Laskey) was explored and was found to enhance the validity of the proposed formulations.

Countertransference↗

Noise reduction in PET attenuation correction by maximum likelihood histogram sharpening of attenuation images.

UNLABELLED: A new method for PET transmission data processing was developed and found to reduce transmission noise in 18F-FDG cardiac emission images. This method is based on a model that describes the measured attenuation image histogram as some unknown true underlying histogram, blurred by noise. METHODS: Emission data from an elliptical phantom (cardiac insert) and three humans were reconstructed using transmission data of varying duration with varying levels of smoothing. Biases and noise levels (cardiac sector analysis) were evaluated for the phantom (simulated replicates) and human emission images. RESULTS: The estimated attenuation histograms typically displayed three distinct peaks corresponding to air, lung and soft tissue without a priori assumptions of the underlying mu values. This method effectively sharpened the histogram peaks and performed well for the phantom and human data. For intermediate transmission noise levels, biases in the phantom sector values were <4%. The human sector results were more variable but consistent with the phantom results. Noise reduction (approximately 30%) was demonstrated across all smooth levels for the phantom data. CONCLUSION: This histogram sharpening method introduces only small bias in the cardiac sector values while achieving an increase in effective transmission scan time of 50-100%. Alternatively, histogram sharpening permits less transmission data smoothing without increased noise.

Algorithms↗

Misalignment between PET transmission and emission scans: its effect on myocardial imaging.

Patient movement between PET scanning sequences can produce misalignment between attenuation and emission scans. Such misalignment introduces errors in the emission image. This study evaluates the severity of these errors and their effect upon quantitation of regional myocardial activity. Myocardial FDG scans from 14 patients were reconstructed with simulated translational, rotational and out-of-plane patient movement. Eight myocardial regions from each patient were examined to determine the effect such misalignment might have on regional myocardial activity. A 2-cm shift between attenuation and emission scans produced up to a 30% change in regional activity. Some regions of the myocardium increased while others decreased for a given magnitude and direction of shift, producing anomalous regional myocardial inhomogeneities in the image. Such changes could easily cause qualitative and quantitative misinterpretations. We present data permitting the reader to assess the magnitude of this effect in his/her own clinical setting.

Cardiomyopathy, Hypertrophic↗

Lung dosimetry of thorotrast patients.

Deposits of intravascularly injected Thorotrast in the reticulo-endothelial system of Thorotrast patients are a continuous source of 220Rn. In this study, we modeled the transport of 220Rn from these deposits through the body into the lungs, exhalation of 220Rn from the lungs, production of 220Rn progeny in the lungs and their exhalation, and mucociliary clearance of 220Rn progeny deposited on airway surfaces. The injection of 1 mL Thorotrast produces annual doses of 0.48 mGy y-1 to the bronchial epithelium and 0.95 mGy y-1 to pulmonary tissue. Based on a mean injected volume of about 25 mL and an average exposure time of 30 y, German Thorotrast patients received a mean bronchial lifetime dose of 357 mGy. Despite these relatively high doses, comparable to exposure in uranium miners, no excess lung cancers could be observed in the epidemiologic follow-up study. This apparent discrepancy between predicted and observed bronchial tumors may have important implications for lung dosimetry and risk assessment of inhaled 222Rn progeny.

Bismuth↗

Depression in a family practice elderly population.

This study addresses several major methodologic issues in the assessment of depressive illness among the elderly family practice living in the community. These include the selection of screening locale, the definition of depression in the elderly, and the evaluation of age trends within this group. The family physician's office is viewed as the optimal screening locale; this facility serves as the chief link between the elderly patient and the community health care system, for psychologic as well as physical complaints. In the definition of depression, a type of depressive illness particularly affecting the elderly may be distinguished from a syndrome more characteristic of depression in the population at large. Emphasis is laid on viewing aging as an evolving process rather than as a steady state. A pilot study of 166 chronically ill family practice patients living in the community was conducted. A large proportion of them, all without previously diagnosed psychiatric impairment, had elevated depression scores according to the Zung Depression Status Inventory. Distinct symptom clusters characteristic of depression in the aged were identified. The data also suggested a systematic age trend, with different peaks of depression for men and women within the elderly age range.

Age Factors↗

On the role of reduced auditory feedback and kinesic self-stimulation during Stroop Color-Word Performance.

Feedback from one's own voice provides important vocal-motor cues for effective cognitive processing. Reduction of such feedback is known to disturb such functioning. Work in our laboratory has shown that kinesic self-stimulation also plays an important role in cognition, and appears to regulate the focusing of attention under conditions of distraction. The present study investigated the effects of both auditory feedback and kinesic self-stimulation in the regulation of cognitive interference during performance of the Stroop Color-Word Task. Twelve subjects were tested on the Stroop task under conditions of normal and occluded hearing. Kinesic self-stimulation and response errors during color-word performance were recorded on video tape. The findings indicated that not only did self-stimulation increase when voice feedback was reduced, but that this increase was associated with a reduction in specific types of color-word performance errors. Individual differences revealed that high kinesic responders made significantly fewer errors in task performance than did low kinesic responders. Results were interpreted as revealing a kinesic feedback mechanism which has adaptive significance in regard to self-editing when auditory feedback is reduced.

Adolescent↗

Effect of vocal feedback on Stroop Color-Word interference.

The present study tested the hypothesis that vocal feedback affects the interference obtained during performance on the Stroop Color-Word task. Two measures were studied as indicators of ability to name colors on the Stroop, speed (performance time) and accuracy (number of errors). Speed of performance on the interference task by 16 male college students was not aided by reduction of vocal feedback. Accuracy of performance in the interference condition was strongly facilitated by reduction of vocal feedback, while little change was noted with no interference. These results are consistent with a view that in vocal feedback on Stroop interference the experience of a mismatch between the auditory feedback produced by the weaker color-naming response in the presence of the prepotent tendency to make the reading response increases interference.

Adolescent↗