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Biomedical subjects

L Levy

Publications and source records attributed to L Levy.

At least 199 records · Page 11Linked to original sources
PubMed1976

Dapsone chemotherapy of Mycobacterium leprae infection of the neonatally thymectomized Lewis rat.

In order to learn whether the neonatally thymectomized Lewis rat (NTLR) infected with Mycobacterium leprae could serve as a model for chemotherapeutic studies in a situation resembling that found in human lepromatous leprosy, NTLR inoculated with M. leprae either locally or intravenously 9 to 16 months earlier were treated for from 1.5 to 8.5 months with dapsone (4,4'-diaminodiphenylsulfone, DDS) incorporated in the rat chow in the concentration providing the minimal inhibitory concentration of the drug for M. leprae and in the 100-fold larger concentration. NTLR were killed at intervals; the M. leprae were counted and passed to mice. Treatment with the smaller dosage of dapsone neither killed M. leprae nor reduced the number of organisms in the bacterial populations, whereas treatment with the larger dosage both killed M. leprae and reduced their numbers. The rate at which the organisms were killed (i.e., rendered noninfective for mice) was much the same as that in patients treated with dapsone in comparable dosage. The dead organisms were removed from the rat tissues at a faster rate than encountered in patients. The NTLR may indeed be suitable for chemotherapeutic studies relevant to man. In addition, the more rapid disappearance of dead M. leprae from the rat tissues may facilitate the study of treatment regimens designed to eradicate persisting viable organisms.

Animals↗
PubMed1976

The pharmacology of flazalone: a new class of anti-inflammatory agent.

The anti-inflammatory activity of flazalone, a unique chemical drug, is described. In acute irritant anti-inflammatory tests, flazalone exhibited a wide spectrum of activity. The compound was active in affecting the course of paw swelling in adjuvant arthritis when given daily either at the outset of the polyarthritis or after induction. The most unusual aspect of this compound is its ability to inhibit graft rejection in goldfish and rabbits. The pattern of anti-inflammatory activity does not allow one to classify this drug in the usual groups.

Adrenal Glands↗
PubMed1975

The effect of cyclophosphamide and methotrexate on the 'field effect' or unresponsiveness observed in the rat and mouse GvHR.

The Field effect is the decreased biological response to a second challenge in the graft versus host reaction (GvHR). Treatment of recipeint rats or mice during the initial GvHR by methotrexate or cyclophosphamide effected the secondary unresponsivienss. Methotrexate and cyclophosphamide demonstrated different temporal responses indicating different mechanisms of their immunosuppresdive activities.

Animals↗
PubMed1975

The incidence of typical and atypical A-V Wenckebach periodicity.

The classic pattern of the typical WP's consists of (1) progressive lengthening of the P-R intervals with the largest increment occuring in the second conducted beat, (2) progressive decrease in P-R increment which accounts for the progressive shortening of successive R-R intervals, and (3) the pause produced by the nonconducted P-wave is less than two P-P intervals. In 45 patients with atrial pacing-induced Wendkebach periods of A-V conduction, the structure of these was studied with His bundle recordings. Of the 128 periods analyzed exceeding 3:2 A-V conduction ratios, 66 per cent were atypical. In 24 patients with spontaneous WP's of A-V conduction, the electrocardiographic records were studied. Of the 98 periods analyzed exceeding 3:2 A-V conduction ratios, 86 per cent were atypical. WP's with A-V conduction ratios greater than 6:5 were all atypical. Five categories of atypical WP's are described.

Bundle of His↗
PubMed1975

Cancer and ageing in mice and men.

In an experiment involving 950 mice with a normal lifespan of 2-3 years, in laboratory conditions, regular benzpyrene application to the skin was started at 10, 25, 40 or 55 weeks of age. The incidence rate of malignant epithelial tumours among the survivors in each group increased steeply with time. This increase was associated directly with duration of exposure but, given duration, was independent of age at the start of exposure, as were the growth rates of already established tumours. In our experiment, although age per se was irrelevant, the cancer incidence rate increased approximately as a power of the duration of exposure to benzpyrene. This shows that the observed approximate power-law increase of most human adult cancer incidence rates with age could exist merely because age equals duration of exposure to background and spontaneous carcinogenic stimuli. Thus, no intrinsic effects of ageing (such as failing immunological surveillance or age related hormonal changes) whatever need to postulated to explain the vast increases in old age of the incidence rates of such human cancers. This result can greatly simplify speculation about mechanisms of carcinogenesis.

Age Factors↗
PubMed1975

Renal and biliary disposition of dapsone in the dog.

Dapsone (4,4'-diaminodiphenylsulfone [DDS]) was administered intravenously to anesthetized dogs; urine was collected, heparinized venous blood was obtained, and bile was collected from some of the dogs. A constant infusion of inulin was maintained, and isosmotic or hypoosmotic fluids were administered. Dogs were studied under conditions of standardized, increased or decreased urine flow, and before and after plasmapheresis. Plasma, urine, and bile samples were analyzed for DDS and DDS conjugates; the degree of binding of DDS by plasma proteins was also determined. The renal clearances of inulin and DDS were calculated. No monoacetyldapsone (MADDS) was detected in the plasma, and only negligible quantities were found in the urine. Small quantities of DDS and DDS conjugates were detected in the bile in 4 h following the dose. Between 10 and 30% of the administered drug could be identified as DDS plus DDS conjugates in the urine in 8 h after the dose. Renal clearance of unbound DDS was proportional to the urine flow rate, and the clearance ratio of DDS to inulin approached the same maximal value as that for urea. Although the rate of urinary excretion of DDS conjugates was the same in the dog as in man, the rates of excretion of DDS and of DDS plus DDS conjugates were greater in the dog than in man, suggesting that the acetylation of DDS to MADDS by man but not by the dog and the greater degree of plasma protein binding of DDS and MADDS by man account for the longer half-time of disappearance of DDS in man compared to that in the dog.

Animals↗
PubMed1975

Minimal inhibitory concentration of dapsone for Mycobacterium leprae in rats.

To define the minimal inhibitory concentration (MIC) of dapsone (DDS) for Mycobacterium leprae in rats, we determined the relationship between dietary and plasma levels of DDS in uninfected male and female Lewis rats. This knowledge was applied to the design of experiments using rats inoculated in the footpads with M. leprae. The MIC for DDS in male and female rats, respectively, was 1.5 to 4.0 ng and 1.8 to 3.0 ng of DDS/ml of plasma, even though the sexes exhibited markedly different concentrations of DDS when receiving the same dietary level of DDS. These values for the MIC of DDS for M. leprae in rats are nearly identical to the previously determined MIC of DDS for M. leprae in mice.

Animals↗
PubMed1975

Superinfection in mice previously infected with Mycobacterium leprae.

Previous studies of the protection of mice by prior infection with Mycobacterium leprae in one hind footpad against challenge with M.leprae in the opposite hind footpad had produced conflicting results; therefore, the problem was restudied. In several experiments, BALB/c mice were inoculated first in the right hind footpad with 5,000 M. leprae and then challenged in the left hind footpad with 5,000 M. leprae of the same strain at intervals after primary infection, at the same time that uninfected mice were inoculated. Multiplication of the M. leprae of the secondary challenge inoculum occurred at the same rate and to the same level as multiplication in uninfected mice when challenges were made soon after primary infection. Multiplication was slowed but proceeded to the same level in previously infected as in uninfected mice when the challenges were administered between 76 and 106 days after primary infection (47 to 17 days before the M. leprae of the primary inoculum had multiplied to the level of 10-6 organisms per footpad). Finally, the M. leprae of a secondary challenge administered at the time that the organisms of the primary inoculum had multiplied to 10-6 per footpad or later not only multiplied more slowly in previously infected than in control animals, but multiplication in the previously infected animals reached a lower maximum. These results are similar to those observed when mice previously infected with M. bovis (BCG), M. marinum, Toxoplasma gondii, or Besnoitia jellisoni were challenged with M. leprae.

Animals↗
PubMed1975

Susceptibility of thymectomized and irradiated mice to challenge with several organisms and the effect of dapsone on infection with Mycobacterium leprae.

B6C3F1 mice that had been thymectomized at 8 to 12 weeks of age, subjected to 950 R of whole-body X irradiation, and transfused with syngeneic bone marrow were challenged in a footpad with Mycobacterium leprae or M. marinum, or intravenously or intraperitioneally with Listeria monocytogenes. Also, mice inoculated with M. leprae in a hind footpad were administered dapsone in the mouse chow. The thymectomized-irradiated (T + R) mice did not survive as well as non-thymectomized mice when housed in the vivarium with no special precautions, but survived sufficiently well to permit the completion of some long-term experiments. M. leprae multiplied to a higher "ceiling" and survived longer in the T + R mice than in the non-thymectomized controls. But a ceiling to multiplication of M. leprae was imposed, and finally the organisms were killed. The histopathological appearance of the footpad tissues, studied by electron microscopy, was consistent with the measurements of bacterial numbers and viability. Swelling of the footpad after local inoculation with M. marinum was greater in T + R mice than in non-thymectomized controls. Similarly, the number of L. monocytogenes following intravenous challenge was greater in the spleens of T + R than of non-thymectomized mice, and the survival of the T + R mice was impaired after intraperitoneal challenge with L.monocytogenes, compared to the survival of non-thymectomized mice. None of these differences was striking, suggesting that these T + R mice had retained or regained some immune competence. The effects of dapsone treatment of T + R mice inoculated with M. leprae were much the same as those of treatment of non-thymectomized mice. Because these T + R mice were not greatly immunosuppressed, they would not have provided a model of human lepromatous leprosy suitable for chemotherapeutic studies.

Animals↗
PubMed1975

A study of the dynamic relations between the mitral valve echogram and phasic mitral flow.

Echocardiographically recorded mitral valve motion was compared with phasic transmitral flow in 17 open chest dogs. The normal mitral valve opening started with the onset of mitral flow and reached its full excursion while flow was still accelerating. Complete valve opening occurred .044 sec (plus or minus .002 sem) before peak flow, during which time an average of 17.6 percent of total mitral filling volume had passed through the valve. In contrast to the opening movement, the closing motion of the anterior mitral valve cusp lagged behind the deceleration of mitral flow. The E-F phase of the mitral valve echogram started while mitral flow was still increasing and resulted from a combined posterior motion of the cusp and the ring. The E-F slope of the normal valve was found to decrease with reduced cardiac output. The amplitude of the anterior cusp excursion did not reflect the amount of mitral flow. Prolonged P-R interval may induce a mid-diastolic reversal of mitral flow which, in turn, may be accompanied by partial or complete valve closure, occurring before the onset of ventricular contraction. Such premature closure of the mitral valve may be accompanied by a certain amount of regurgitant flow.

Animals↗
PubMed1975

Inhibition of multiplication of Mycobacterium leprae by several antithyroid drugs.

Multiplication of Mycobacterium leprae in the mouse footpad was inhibited when mice were fed, mixed in their diet, 0.05 per cent methimazole, 0.066 per cent USP thyroid powder, methimazole plus thyroid powder, 0.15 per cent 5-n-heptyl-2-thioxo-4-thiazolidinone, 0.1 per cent propylthiouracil, and 0.1 per cent thambutosine for 154 days, beginning on the day of inoculation. All of the treatment regimens, except for the 2 containing thyroid powder, decreased the plasma concentrations of thyroxine and protein-bound iodine. It is suggested that the 2 antithyroid drugs, methiomazole and propylthiouracil, and the 2 antimicrobial agents, heptylthioxothiazolidinone and thiambutosine, all of which possess structural features in common, may exert the antithyroid and antimicrobial effects through a common mechanisms.

Aniline Compounds↗
PubMed1975

The activity of chaulmoogra acids against Mycobacterium leprae.

The activity of the crude sodium salts of the fatty acids of chaulmoogra oil and of hydnocarpic and chaulmoogric acids against Mycobacterium leprae was studied in mouse footpad infection. Multiplication of the organisms was inhibited when the salts were administered intraperitoneally and subcutaneously 3 times per week, and when chaulmoogric acid was administered intraperitoneally 5 times per week in half the equivalent dose. Dihydrochaulmoogric acid was also active, whereas palmitic acid was not. Hydnocarpic acid administered intraperitoneally once per week in a dose equivalent to half that of the sodium salts of the chaulmoogra fatty acids was not effective. The demonstration that chaulmoogra fatty acids possess activity against M. leprae lends weight to our earlier suggestion that a study of compounds analogous to these acids may yield effective antimicrobial agents with a unique mechanism of action.

Animals↗
PubMed1975

The state mental hospital in transition. Illinois state mental hospitals decentralize.

In this paper, we have looked at mental hospital decentralization as it has developed in the thirteen State of Illinois mental hospitals as of June 30, 1967. The hospitals were looked at from the most centralized to the most decentralized. This was done by relating the hospitals to five descriptive model types, described at greater length elsewhere. Hospital decentralization is portrayed as a complex and highly idiosyncratic process. Attempts to place specific hospitals at point along the decentralization continuum are thus tentative and clear rules for classifying stages of decentralization have yet to be formulated. Complicating the picture still further is that hospitals in transition change rapidly and may at even intervals of a month show dramatic change. It is expected that the trend implied is stable, however, and that ultimately all Illinois state mental hospital with possible exception of ISPI and Illinois Security Hospital, will be located at the decentralized model. This is seen as necessary if they are to survive as viable treatment institutions.

Commitment of Persons with Psychiatric Disorders↗