PubMed HealthSearch

Biomedical subjects

C C Shepard

Publications and source records attributed to C C Shepard.

At least 19 recordsLinked to original sources

Activity of selected beta-lactam antibiotics against Mycobacterium leprae.

Twelve beta-lactam antibiotics were tested for activity against Mycobacterium leprae growing in the foot pads of mice. Two cephalosporins (7-aminocephalosporanic acid and cefuroxime) and one cephamycin (cefoxitin) showed significant activity against M. leprae, and one penicillin (mezlocillin) exerted possible growth-promoting activity. These results suggest that particular molecular structures may be required for activity against M. leprae.

Animals

Susceptibility of strains of Mycobacterium leprae isolated prior to 1977 from patients with previously untreated lepromatous leprosy.

Because of the recent spate of reports of primary resistance to dapsone among patients with lepromatous leprosy, largely to small concentrations of the drug, a survey was made of the results of dapsone-susceptibility testing of strains of Mycobacterium leprae isolated before 1977 among six laboratories which employed the mouse foot pad technique for this work prior to that time. Data have been found for strains that had been isolated from 73 patients, representing 19 countries and dependencies, with previously untreated lepromatous leprosy; all 73 strains were inhibited from multiplication by dapsone administered to mice in a concentration of 0.0001 g per 100 g mouse diet. These data suggest that the properties of M. leprae isolated from previously untreated patients with respect to susceptibility to dapsone have changed since the years preceding 1977.

Animals

An experimental study of the antileprosy activity of a series of thioamides in the mouse.

A series of substituted thioamides have been studied to establish whether their structure-activity pattern against Mycobacterium leprae is similar to that displayed against M. tuberculosis. Antileprosy activity was evaluated in the mouse foot pad using both the kinetic and continuous methods. Ethionamide and prothionamide were found to be the most active compounds and to be of approximately equal potency. Thioisonicotinamide was about five times less active. 2-t-Butyl-thioisonicotinamide, 2-dimethylamino-thioisonicotinamide, and pyrazine carbonic thioamide were inactive at the dosages tested. High-pressure liquid chromatographic methods were devised to study the potential influence of pharmacological factors on their in vivo activity. Fecal measurements suggested that all of the thioamides were well absorbed when fed in the diet. After intravenous administration, all of the thioamides were rapidly eliminated from the mouse. The differences in their elimination rates probably played only a minor role in affecting their relative antileprosy activities. It was concluded that the structural requirements for antileprosy and antituberculosis activity of the thioamides are probably similar.

Amides

2-Acetylpyridine thiosemicarbazones and Mycobacterium leprae.

Four 2-acetylpyridine thiosemicarbazones were tested in mice against Mycobacterium leprae by the kinetic method and found to be nearly inactive in a dosage of 0.05% in the diet. At the same dosage, thiacetazone, as a positive control, exhibited its expected activity.

Animals

Comparison of the immunogenicity of vaccines prepared from viable Mycobacterium bovis BCG, heat-killed Mycobacterium leprae, and a mixture of the two for normal and M. leprae-tolerant mice.

Intradermal vaccines consisting of viable Mycobacterium bovis BCG, heat-killed Mycobacterium leprae, or mixtures of the two were titrated in mice in doses of 10(5.2), 10(5.8), 10(6.4), 10(7.0), and 10(7.6) acid-fast bacilli. The immune response was measured by sensitization (48 to 72 h foot pad enlargement on challenge with 10(7.0) heat-killed M. leprae) and by protection against infection with a viable M. leprae challenge. There was increasing response with increasing dose of vaccine, and overall the responses to the three vaccines were similar. At the lowest dose, however, the combination of BCG and M. leprae gave superior protection. The local reaction to the vaccines in the lower dose range was less severe with the M. leprae vaccine. In another experiment, the three vaccines were compared in normal mice and in mice that had been rendered tolerant by intravenous injection of M. leprae. The tolerant mice developed no measurable sensitization on vaccination with M. leprae, but they developed partial but distinct sensitization on vaccination with BCG, alone or in combination with M. leprae. The tolerant mice developed little or no protection with any of the vaccines, however.

Animals

Evidence of Rickettsia prowazekii infections in the United States.

From January 1976 through January 1979 serum specimens from 1,575 individuals were received at the Center for Disease Control and tested for antibodies to rickettsiae. Of these, sera from eight persons gave serological results indicative of recent infections with epidemic typhus rickettsiae (Rickettsia prowazekii). Five of the persons were from Georgia, and one each was from Tennessee, Pennsylvania and Massachusetts. The illnesses occurred during the winter, chiefly in persons living in a rural environment. The clinical picture was compatible with louse-borne epidemic typhus. There was no apparent contact with human body or head lice, and no cases occurred in patient contacts, indicating that infection was not associated with the classic man-louse-man cycle of epidemic typhus. Two of the eight patients had contact with flying squirrels suggesting that they became infected from this known extrahuman reservoir of R. prowazekii.

Adolescent

Virulent to avirulent conversion of Legionnaires' disease bacterium (Legionella pneumophila)--its effect on isolation techniques.

Suspensions of the Legionnaries' disease bacterium (Legionella pneumophila; LDB) were prepared from the yolk sacs of infected egg embryos, the spleens of infected guinea pigs, and cultures of the organism propagated on enriched Mueller-Hinton agar. Each suspension was titrated to determine the number of bacterial colonies (cfu), yolk sac 50% lethal doses (YSLD50), guinea pig 50% infectious doses (GPID50), and guinea pig 50% lethal doses (GPLD50) produced by 1 ml of inoculum. The numbers of cfu/YSLD50, GPID50, and GPLD50 were then calculated for each suspension. The suspension from yolk sacs had 1 cfu/YSLD50 and 10 cfu/GPID50. The suspension from spleens of guinea pigs also had 1 cfu/YSLD50. Organisms propagated on Mueller-Hinton agar, however, had greater than 10(7) cfu/YSLD50 and 10(5) cfu/GPID50. Thus, the LDB lost virulence when it was cultivated on agar. Guinea pigs vaccinated either subcutaneously or intraperitoneally with LDB grown on Mueller-Hinton agar resisted challenge with virulent LDB.

Animals

A comparison of the complement fixation, indirect fluorescent antibody, and microagglutination tests for the serological diagnosis of rickettsial diseases.

Three techniques for the serological diagnosis of Rocky Mountain spotted fever were compared by testing 417 sera from 178 patients who very probably did not have rickettsial infections and 88 sera from 41 patients who very probably had Rocky Mountain spotted fever (SF). The techniques were complement fixation (CF), indirect fluorescent antibody (IFA), and microagglutination (MA). To avoid possible degradation during unnecessary purification, the antigens were prepared by methods that were as simple as possible. In the CF tests of 417 sera from patients with nonrickettsial diseases there was only one titer of 8 and none at higher dilutions, whereas with the IFA and MA tests 4-8% of the sera reacted with SF antigens and 4-20% reacted with murine typhus (MT) antigens; the evidence indicated that these reactions were not caused by specific rickettsial antibody. With the SF sera, it could be seen that the IFA test was the most sensitive and the MA test was the least sensitive at each interval after infection. Moreover, the IFA results showed the least number of confusing cross-reactions with MT antigens and the MA test showed the most. The relative advantages of the three tests in serodiagnosis of rickettsial diseases are discussed.

Agglutination Tests

Sporadic community-acquired Legionnaires' disease in the United States. A case-control study.

One hundred patients with sporadic, community-acquired, serologically confirmed Legionnaires' disease were matched with control subjects known by the patients (acquaintance controls) and control subjects chosen from among patients with negative serodiagnostic tests for Legionnaires' disease (clinical controls). Each clinical control subject was also matched with an acquaintance control of his own. Legionnaires' disease patients had smoked more cigarettes, consumed more alcohol, and were more likely to have resided near excavation sites than acquaintance or clinical control subjects. Parallel differences between clinical controls and their acquaintances were not seen. Legionnaires' disease patients had traveled away from home for more time during the 2 weeks before onset of illness than had their acquaintances. The difference was of greater magnitude than that between clinical control subjects and their acquaintances. Legionnaires' disease patients were more likely to have resided near construction sites than clinical controls, and there were more construction workers among patients than among clinical control subjects.

Adult

Acedapsone in the prevention of leprosy: field trial in three high prevalence villages in Micronesia.

The 1,659 non-leprous people in a Micronesian population experiencing an annual leprosy incidence rate of about 7/1,000 were offered 15 acedapsone (DADDS) injections during 1967--1970 for leprosy prevention purposes. Subsequent annual surveillance showed an initial cessation of new cases during the 3-year DADDS campaign, followed by a resumption of cases thereafter at a yearly level of about 2/1,000 with a longer pause and slower rise among those who received the full regimen. A secondary wave of cases that has occurred since 1973 among children born after 1968 shows that post-campaign transmission occurred, probably principally from relapsing multibacillary cases with onset before the campaign. Recommendations are made for a balanced, long-term control program with DADDS preventive treatment limited to contacts of multibacillary cases.

Acedapsone

An outbreak in 1965 of severe respiratory illness caused by the Legionnaires' disease bacterium.

In January 1977 an unsolved outbreak of infection at St. Elizabeth's Hospital (Washington, D.C.) that occurred in 1965 was linked with Legionnaires' disease. The link was made by fluorescent antibody testing with the bacterium isolated from tissues of persons with Legionnaires' disease in the 1976 outbreak in Philadelphia. In July and August 1965, an epidemic of severe respiratory disease characterized by abrupt onset of high fever, weakness, malaise, and nonproductive cough, frequently accompanied by radiographic evidence of pneumonia, affected at least 81 patients at St. Elizabeth's Hospital, a general psychiatric hospital. Fourteen (17%) of the affected patients died. Intensive epidemiologic and laboratory investigations in 1965 did not determine the etiology. The etiologic organism may have become airborne from sites of soil excavation.

Air Microbiology