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Biomedical subjects

L Friedman

Publications and source records attributed to L Friedman.

At least 235 records · Page 13Linked to original sources

Teratological research using in vitro systems. II. Rodent limb bud culture system.

This review represents a compilation of information related to the rodent limb bud culture system from approximately 80 publications after 1969 and conversations with workers in the field. Most of these papers and book chapters refer exclusively to studies with the mouse limb bud. Sections in this review include historical review, end point measurements, activating systems, types of compounds studied and dose response, reproducibility, statistical analysis, equipment and personnel requirements, mechanisms, and summary.

Animals↗

Monitoring boundaries for adverse effects in long-term clinical trials.

The typical long-term trial has a data monitoring committee. A primary responsibility of this committee is maintenance of patient safety. In this role, this committee is likely to recommend stopping a trial when a new treatment appears worse than the control even when the difference is not statistically significant or if it appears that the new treatment will not be clearly beneficial. Several approaches, including the use of conditional power, can be used to help the monitoring committee decide if a study should be stopped early because of a harmful or insufficiently effective treatment. These monitoring approaches have altered the way in which we view one-sided or two-sided tests of significance.

Clinical Trials as Topic↗

Fifteen year mortality in Coronary Drug Project patients: long-term benefit with niacin.

The Coronary Drug Project was conducted between 1966 and 1975 to assess the long-term efficacy and safety of five lipid-influencing drugs in 8,341 men aged 30 to 64 years with electrocardiogram-documented previous myocardial infarction. The two estrogen regimens and dextrothyroxine were discontinued early because of adverse effects. No evidence of efficacy was found for the clofibrate treatment. Niacin treatment showed modest benefit in decreasing definite nonfatal recurrent myocardial infarction but did not decrease total mortality. With a mean follow-up of 15 years, nearly 9 years after termination of the trial, mortality from all causes in each of the drug groups, except for niacin, was similar to that in the placebo group. Mortality in the niacin group was 11% lower than in the placebo group (52.0 versus 58.2%; p = 0.0004). This late benefit of niacin, occurring after discontinuation of the drug, may be a result of a translation into a mortality benefit over subsequent years of the early favorable effect of niacin in decreasing nonfatal reinfarction or a result of the cholesterol-lowering effect of niacin, or both.

Adult↗

Modification of paradoxical sleep following transections of the reticular formation at the pontomedullary junction.

A retractable wire knife was employed to transect the reticular formation at the pontomedullary junction in order to assess the respective importance of pontine and medullary reticular neurons and their pathways in paradoxical sleep. Thirteen cats were implanted with a standard array of electrodes for polygraphic recording of sleep-wakefulness states during 3 days in baseline condition and during 21 days after transections. Average electroencephalographic (EEG) amplitude, average electromyographic (EMG) amplitude, and ponto-geniculo-occipital (PGO) spike rate were measured per 1-min epoch for each day. A trivariate computer graphics display of 1 day's data revealed three major clusters of points that corresponded to wakefulness, slow wave sleep, and paradoxical sleep in baseline. (a) After transections through the entire reticular formation at the pontomedullary junction, paradoxical sleep was no longer evident in the trivariate computer graphics or polygraphic record, either by the presence of a high PGO spike rate or by that of muscle atonia in association with a low-amplitude EEG. These results indicated that the reticular fibers that pass through the pontomedullary junction and interconnect the pontine tegmentum and the medullary reticular formation are necessary for generating the cluster of electrographic variables that normally characterizes paradoxical sleep. (b) After transections through the dorsal half of the reticular formation, paradoxical sleep was still evident, though with a reduced PGO spike rate, and muscle atonia was normal. These results indicated that the descending noradrenaline locus coeruleus fibers and the "longitudinal catecholamine bundle," which course through the dorsal tegmentum, are not necessary for the generation of muscle atonia or the state of paradoxical sleep. (c) After transections through the ventral half of the reticular formation, paradoxical sleep was still apparent by the association of a moderate, though reduced, rate of PGO spiking in association with low-amplitude EEG activity and a high-amplitude EMG, indicating a loss of muscle atonia. The duration of the PS episodes, however, was greatly reduced. These results indicated that the descending "tegmentoreticular" and ascending reticulotegmental pathways, which course ventrally through the pontomedullary junction and interconnect the dorsolateral pontine tegmentum and the ventromedial medullary reticular formation, are essential for the muscle atonia of paradoxical sleep and important for the normal cyclic generation and maintenance of the state of paradoxical sleep.

Animals↗

Weight changes in antidepressants: a comparison of amitriptyline and trazodone.

Weight data taken from a 6-week randomized double-blind study comparing amitriptyline, trazodone and placebo were analyzed to determine differential weight changes between the two drugs. In 272 depressed outpatients doses were increased over a period of 4 days to reach a maximum level of 200 mg amitriptyline or 400 mg trazodone. After grouping the subjects according to initial weights (ideal, overweight, 20% above, and underweight, 20% below) mean changes were determined for each treatment. The results indicate that amitriptyline, which differed from placebo and trazodone, produced significantly higher weight gains in the ideal and overweight groups. Trazodone on the other hand produced a slight weight loss in the overweight group. Due to a low number of patients in the underweight group, the results were not significantly statistically. The antidepressant effects of both trazodone and amitriptyline were the same and no correlations between Hamilton scores and weight change were found.

Adolescent↗

Macromolecular levels, DNA synthesis and ornithine decarboxylase activity in leg muscles from 6-mercaptopurine-treated rats.

Sprague-Dawley male and female rats were treated with 6-mercaptopurine (6-MP) (2 mg/kg sc) daily from 2 to 22 days of age and killed at 7, 15, 27 and 64 days of age. At 7 and 27 days of age rats were injected with 3H thymidine for measurement of DNA synthesis. Fore- and hindlimb muscles were removed and analyzed for ornithine decarboxylase (ODC) activity (all ages), DNA radioactivity (7 and 27 days), DNA level (27 and 64 days) and RNA level (64 days). As expected, ODC activity and DNA synthesis were higher in muscles of 7-day-old rats than in muscles of the older rats studied. A consistently lower ODC activity was seen in 6-MP-treated vs. control rats for 5-25 days after start of treatment, but the effect was essentially the same for the hindlimb and forelimb muscles. During the 7-27-day time course ODC activity was higher in hindlimb than forelimb muscles. By 27 days of age DNA synthesis was also higher in the hindlimb muscles. DNA synthesis was decreased after 5 days of treatment relative to that of control rats, to an approximately equal extent in forelimb and hindlimb muscles. Five days after the last treatment a trend was seen for slower recovery from inhibition of DNA synthesis in hindlimb muscles, particularly in male rats. DNA levels were reduced in treated rats relative to those in control rats 5 days after the last treatment to approximately the same degree in forelimb and hindlimb muscles. Forty-two days after the last treatment a trend toward increased activity of ODC and increased DNA and RNA levels was seen in muscles of treated rats, probably reflective of recovery processes. These early biochemical effects of 6-MP, which were seen to about the same extent in the forelimb and hindlimb muscles cannot explain by themselves the delayed hindlimb fat atrophy resulting from 6-MP treatment of neonatal rats.

Animals↗

The stability of DNA in human cerebellar neurons.

Human tissues have carbon-isotope ratios (13C/12C) that reflect dietary ratios. This observation has been used to determine the extent of metabolic turnover of DNA in cells of the adult human cerebellum (90 percent of which are neuronal). If adult human neuronal DNA were metabolically stable, its 13C/12C would reflect that in the maternal diet during fetal development as nearly all neurons are formed during maturation of the fetal brain and do not undergo cell division thereafter. The 13C/12C ratios in the food chains and body tissues of Europeans differ from corresponding American ratios by about 50 parts per million on the average. Therefore, turnover was studied by comparing 13C/12C ratios in cerebellar DNA of American-born Americans, European-born Americans, and European-born Europeans. The 13C/12C ratios in cerebellar DNA from European-born Americans were closer to 13C/12C ratios in cerebellar DNA from European-born Europeans than from American-born Americans, indicating that there was little or no turnover of neuronal DNA.

Adult↗

Histopathology of the subretinal fibrosis and uveitis syndrome.

A chorioretinal biopsy was obtained from a patient with subretinal fibrosis and chronic uveitis. The biopsy specimen was analyzed by conventional light and electron microscopy and by immunohistochemical methods. These demonstrated a markedly inflamed choroid with a predominance of B cells and plasma cells. Complement and IgG were deposited above Bruch's membrane. The subretinal fibrosis tissue contained islands of cells with retinal pigment epithelial characteristics; however, some of these cells demonstrated surface determinants of Müller cells. There were no circulating antiretinal antibodies detected nor could virus be cultured from the biopsy specimen. The clinical appearance of this entity is distinctive and consists of a chronic posterior uveitis with transient initial yellow-white deep retinal lesions and the later development of large white subretinal fibrotic areas. The EOG is markedly decreased. We hypothesize that the immunologic events involved in this entity include antibody production with immunoglobulin and complement deposition leading to retinal and retinal pigment epithelial destruction and a subretinal fibrous proliferation.

Adolescent↗

Motivation, vocational interests and job satisfaction of mentally retarded adults.

The relationship between vocational interests of 83 mildly to moderately retarded adults in a residential facility in Israel, their actual work and the factors which they perceived as the most important motivators for them at work and job satisfaction were investigated. Two questionnaires were used: the Illustrated Vocational Inventory (Whelan & Reiter, 1980) and a specially designed questionnaire on motivation to work based on Herzberg, Mausner, and Snyderman's (1959). The results demonstrate the importance of taking into consideration mentally retarded persons' vocational interests when assignig them to different jobs. It further demonstrates the importance of the environment in influencing mentally retarded individuals to seek instrinsic or extrinsic rewards and satisfaction from work.

Adult↗

Potentiality shrouded: how the newer theories work.

An analyst often needs to feel that the integration he anticipates and provokes was already observed, fully present, in the patient. He can feel that way by cultivating an empathic sense that the patient's aspects and movements are inevitable and not chosen. A full theory of the mind, however, describes other possibilities. For that reason, it is sometimes useful to work with incomplete theories that omit descriptions of potentiality. These holistic revisions of psychoanalysis increase the variety of passively perceived treatment-relevant configurations and lessen the analyst's descriptive authority.

Conflict, Psychological↗

Radiographic and computed tomographic findings in lipid proteinosis. A case report.

A case of lipoid proteinosis in an 18-year-old youth is presented. The typical clinical findings in patients with this rare disorder are discussed. Emphasis is placed on the radiographic and computed tomographic appearances. The bean-shaped calcific densities, which are located in the region of the hippocampi in this case, are illustrated.

Adolescent↗

Study of sleep-wakefulness states by computer graphics and cluster analysis before and after lesions of the pontine tegmentum in the cat.

A computerized method of quantification, graphic representation and classification of sleep-wakefulness data in the cat before and after pontine tegmental lesions has been presented. Electrophysiological signal features including average EEG amplitude, average EMG amplitude and PGO spike rate which are particularly important for the definition of sleep-wakefulness states have been quantified for each 1 min epoch in the day. The data were presented in a projected 3-dimensional data display, in which they formed clusters that are considered to be analogous to sleep-wakefulness states. A cluster analysis algorithm was employed for the automatic classification of these data, and this automatic classification was compared graphically and with contingency table analyses to traditional visual assessment of state from polygraphic records. Although there were systematic differences in the locations of state boundaries, total percent agreement between cluster analysis classification and traditional human classification was comparable to the percent agreement between any two human classifiers (about 90%). After pontine tegmental lesions involving both the gigantocellular and lateral tegmental fields, paradoxical sleep was eliminated, and the characteristics of slow wave sleep and wakefulness were altered. The elimination of the state of paradoxical sleep was evident in the computer display by the absence of the paradoxical sleep cluster, and alterations of the other states were indicated in the display by shifts in the positions of their respective clusters. Automatic classification of slow wave sleep and wakefulness after such lesions compared well with traditional classification, attesting to the validity of this approach.

Animals↗