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Biomedical subjects

L Cohen

Publications and source records attributed to L Cohen.

At least 577 records · Page 32Linked to original sources

Diethylstilbestrol effects on serum enzymes and isozymes in muscular dystrophy.

Diethyistibestrol was administered orally to 11 boys with Duchene muscular dystrophy (DMD). Creatine phosphokinase (CPK) and lactate dehydrogenase (LDH) activities, characteristically high in DMD, and presumably of muscle origin, were reduced significantly (P LESS THAN .05). On ther other hand, the activity of alkaline phosphatase, an enzyme not of muscle origin, increased. These enzyme changes were reversible when diethyistibestrol was discontinued. Despite appreciable alterations in totoal serum enzyme activity, no important change was found in the isozyme patterns. Piperazine estrone sulfate was administered to another patient with DMD. The effects of this physiologic hormone were, in part, similar to those of diethyistibestrol. Experimentally, diethylstilbestrol reduced the efflux of CPK and LDH from mouse skeletal muscle. This may be the manner by which diethylstilbesterol reduced the serum enzyme levels in DMD, but this has not been proved directly. These studies are the first step in an effort to identify various agents that in combinations may normalize serum enzyme levels.

Adolescent↗

Survival of patients with lung cancer treated with vincristine and actinomycin D: An unsuccessful trial.

Twenty-five patients with lung cancer were treated with actinomycin-D and vincristine (V-D) with only one objective response (IMD). The survival of these patients was compared retrospectively to a group of 49 consecutive patients treated with radiotherapy only during the same time period. Median survival times for the V-D group and radiotherapy controls were 6.5 and 7.5 months, respectively. It is concluded that V-D did not increase survival in patients with lung cancer and should be dropped from the chemotherapeutic armamentarium in lung cancer.

Dactinomycin↗

Value of Holter monitoring in assessing cardiac arrhythmias in symptomatic patients.

Holter electrocardiographic monitoring in 55 symptomatic patients with syncope, palpitations or dizziness uncovered significant arrhythmias in 30 patients (55 percent). By providing an observation period of at least 24 hours including a period of sleep, the procedure aided detection and diagnosis in both symptomatic and asymptomatic patients of transient arrhythmias or conduction abnormalities not documented by routine electrocardiograms. Bradyarrhythmias accounted for the majority of arrhythmias recorded in 21 or 30 symptomatic patients (70 percent); 15 had sinus bradycardia (35 to 55 beats/min) alone and 6 also had long episodes of sinus arrest of up to 5 seconds. Two had sinus bradycardia with periods of atrioventricular block with Wenckebach phenomenon. Five patients had a tachycardia-bradycardia syndrome; three had other episodic arrhythmias and one had pacemaker failure. In 15 (60 percent) of the 25 patients without arrhythmias, monitoring did not document the cause of symptoms. Holter monitoring is of considerable value in assessing the efficacy and adequacy of drug treatment, especially in patients with known heart disease, and in detecting pacemaker malfunction. However, very long periods of monitoring may be needed to make a diagnosis in those with only sporadic symptoms.

Adult↗

A trial of Fortagesic and Paramol 118 in osteoarthritis.

Fortagesic was compared with Paramol 118 in a fourteen day single-blind crossover study in patients with moderate pain due to osteoarthritis. Both preparations were shown to be similarly effective. More side-effects were seen with Paramol 118 than with Fortagesic and more patients preferred Fortagesic. These differences were not statistically significant, but it is concluded that Fortagesic is a useful effective analgesic for standard use in moderate pain.

Acetaminophen↗

Disparate effects of diethylstillbestrol and prednisolone on enzyme efflux from heart and skeletal muscle.

We have previously shown that diethylstilbestrol (DES) almost always, and prednisolone (Pr) less frequently, lowered the high serum enzyme activities in Duchenne's muscular dystrophy (DMD). In experimental studies, it was shown that pretreatment of mice with each of these agents lowered enzyme efflux from isolated skeletal muscle incubated in vitro, but efflux was augmented by higher doses of Pr. This suggested that these agents may influence skeletal muscle enzyme efflux in man also, producing the effects noted in DMD. The present studies were undertaken to assess the effect on enzyme efflux from skeletal muscle and heart that these two agents would exert when given in combination. Four groups of mice (14/group) were injected with saline, 250 mug DES, 35 mug Pr, or 250 mug DES plus 35 mug Pr in saline every other day for 22 days. The left gastroecnemius and heart were isolated from animals of each group, and placed in separate tubes containing incubation medium at 25 degrees C. The efflux of creatine phosphokinase (CPK) and lactate dehydrogenase (LDH) which issued from each organ was determined over a 5 hour period. In the doses tested, it was found that: 1) DES selectively reduced enzyme efflux from skeletal muscle, but had no effect on enzyme efflux from heart; 2) a Pr dose which decreased enzyme efflux from the heart, augmented efflux from the gastrocnemius; and 3) DES prevented the enhanced enzyme efflux produced by Pr. These studies indicate that these hormones, in pharmacological doses, influence enzyme efflux from muscle. This suggests, but it is not established, that these hormones also exert a similar physiological role. Finally, this experimental model appears to be useful in assessing the effects of single agents, and agents in combination, on enzyme efflux, and should be of aid in selecting appropriate agents which may be therapeutically useful in Duchenne's muscular dystrophy.

Animals↗

Reduction of enzyme efflux from skeletal muscle by diethylstilbestrol.

We have previously shown that oral diethylstilbestrol (DES) lowers the high serum enzyme levels characteristic of Duchenne's muscular dystrophy (DMD). The present studies were undertaken to assess the effect of DES on the efflux of enzymes from isolated mouse skeletal muscle. Thirty-four male mice were used. Half received daily subcutaneous injections of 10 mug diethylstilbestrol-diphosphate (DES-DP) in saline for up to 3 wk and half daily saline injections. Left gastrocnemii were isolated from control and treated mice, and placed in separate incubation media at 37 degrees C. The efflux of creatine phosphokinase (CPK) and lactate dehydrogenase (LDH) from each was compared over a 4- to 5-hr period. In 15 of 18 there was a reduction in efflux of both enzymes from muscles isolated from DES-DP-treated mice. The greatest effect was noted during the second hour, when the mean efflux of each enzyme was reduced about 30%. Minor differences in muscle weight, water content, and enzyme activities did not explain the reduced efflux. These results suggest that DES has either reduced the permeability of the sarcolemma or enhanced the intracytoplasmic stability of these enzymes. This is the first drug reported to reduce the spontaneous enzyme efflux from isolated skeletal muscle. It remains to be established that a similar effect accounts for the reduction in serum enzyme levels when DES is administered to persons with DMD.

Animals↗

Acid-soluble degradation products of ribonucleic acid in Escherichia coli and the role of nucleotidases in their catabolism.

The fate of the internally formed nucleotides resulting from the degradation of ribonucleic acid was studied. Prelabeled Escherichia coli cells were submitted to carbon starvation, and the acid-soluble products were separated by thin-layer chromatography. It was determined that free bases constitute some 75% of the end product, the balance consisting of nucleoside diphosphates, 5'-nucleoside monophosphates, 3'-nucleoside monophosphates, and nucleosides. The majority of degradation products, including phosphorylated derivatives, were excreted into the medium. The amount of products in the pool remained constant. The soluble products formed by E. coli mutants lacking either 5'-nucleotidase (Ush-) or 3'-nucleotidase (Cpd-) were compared with those produced by the parental strain with both enzymes. The results obtained indicated that 5'-nucleotidase is involved in the degradation of internally foromed nucleotides but that 3'-nucleotidase takes no part in the process.

Carbon↗