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Biomedical subjects

B Ji

Publications and source records attributed to B Ji.

At least 55 records · Page 3Linked to original sources
PubMed1996

Bactericidal activities of combinations of new drugs against Mycobacterium leprae in nude mice.

The bactericidal activities of 12 regimens with various combinations of new drugs (clarithromycin [CLARI], minocycline [MINO], and ofloxacin [OFLO]) and the standard antileprosy drugs, especially rifampin (RMP), were compared in nude mice with established Mycobacterium leprae infection. The longest duration of treatment was 24 weeks for intermittent (once every 4 weeks) therapy and 8 weeks for daily therapy. Bactericidal effects were monitored by titrating the proportion of viable M. leprae isolates by subinoculating the organisms into the footpads of immunocompetent and nude mice. The results indicate that RMP was more bactericidal than any combination of the new drugs. A single dose of CLARI-MINO, with or without OFLO, displayed bactericidal activity as great as that of 4 weeks of daily treatment with dapsone (DDS) plus clofazimine (CLO); thus, intermittent CLARI-MINO, with or without OFLO, may replace DDS and CLO of the standard multidrug regimen, and these will become regimens that can be administered monthly and under full supervision. Additional evidence that this may be the case is provided by the finding that intermittent RMP-CLARI-MINO or RMP-CLARI-MINO-OFLO administered for 12 or 24 weeks was as active as the standard multidrug regimen. While the intermittent treatment always displayed significantly greater bactericidal activity than the same number of doses of daily treatment, daily treatment with CLARI-MINO and CLARI-MINO-OFLO were more active than the drugs given as intermittent treatment for the same duration; therefore, unless these combinations are to be administered together with intermittent RMP, they should be given daily, especially for the treatment of RMP-resistant cases of infection. Finally, 12 weeks of daily treatment with DDS-CLO was more bactericidal than had been expected, suggesting that it may not be necessary to administer the standard multidrug regimen for multibacillary leprosy for as long as 24 months in order to minimize the risk of developing RMP resistance.

Animals↗
PubMed1996

How effective is KRM-1648 in treatment of disseminated Mycobacterium avium complex infections in beige mice?

Although the MICs of 3'-hydroxy-5'-(4-isobutyl-1-piperazinyl)benzoxazinorifamycin, or KRM-1648 (KRM), for Mycobacterium avium complex (MAC) were significantly lower than those of other drugs, its in vivo activity was very weak. Beginning 28 days after inoculation, beige mice that had been infected intravenously with 1.87 x 10(7) CFU of MAC 101 were administered KRM alone, clarithromycin (CLARI) alone, or CLARI plus KRM six times weekly for 16 weeks. In contrast to the mice treated with CLARI-containing regimens, the mortality and the mean spleen weights of mice treated with KRM alone (either 10 or 20 mg/kg of body weight per dose) did not differ significantly from those of untreated mice, their numbers of CFU were very much greater than pretreatment values, and multiplication of MAC was only slightly inhibited. Although monotherapy by KRM selected KRM-resistant mutants, the selection was very weak; the mean number of CFU and the frequency of KRM-resistant mutants increased by no more than 1 order of magnitude after 16 weeks of treatment with KRM at 20 mg/kg per dose. Selection of CLARI-resistant mutants was inhibited but not completely prevented by treatment of the mice with CLARI plus KRM. These results indicate that KRM displayed only a weak bacteriostatic effect against the isolate tested in the beige mouse model; its ability to enhance the antimicrobial effect of CLARI or to prevent emergence of CLARI-resistant mutants was very limited.

Animals↗
PubMed1996

Bactericidal activity of single dose of clarithromycin plus minocycline, with or without ofloxacin, against Mycobacterium leprae in patients.

Fifty patients with newly diagnosed lepromatous leprosy were allocated randomly to one of five groups and treated with either a month-long standard regimen of multidrug therapy (MDT) for multibacillary leprosy, a single dose of 600 mg of rifampin, a month-long regimen with the dapsone (DDS) and clofazimine (CLO) components of the standard MDT, or a single dose of 2,000 mg of clarithromycin (CLARI) plus 200 mg of minocycline (MINO), with or without the addition of 800 mg of ofloxacin (OFLO). At the end of 1 month, clinical improvement accompanied by significant decreases of morphological indexes in skin smears was observed in about half of the patients of each group. A significant bactericidal effect was demonstrated in the great majority of patients in all five groups by inoculating the footpads of mice with organisms recovered from biopsy samples obtained before and after treatment. Rifampin proved to be a bactericidal drug against Mycobacterium leprae more potent than any combination of the other drugs. A single dose of CLARI-MINO, with or without OFLO, displayed a degree of bactericidal activity similar to that of a regimen daily of doses of DDS-CLO for 1 month, suggesting that it may be possible to replace the DDS and CLO components of the MDT with a monthly dose of CLARI-MINO, with or without OFLO. However, gastrointestinal adverse events were quite frequent among patients treated with CLARI-MINO, with or without OFLO, and may be attributed to the higher dosage of CLARI or MINO or to the combination of CLARI-MINO plus OFLO. In future trials, therefore, we propose to reduce the dosages of the drugs to 1,000 mg of CLARI, 100 mg of MINO, and 400 mg of OFLO.

Adolescent↗
PubMed1996

Determination of the minimal effective dosages of ofloxacin and sparfloxacin against M. leprae in the mouse foot pad system.

The minimal effective dosages (MEDs) of ofloxacin (OFLO) and sparfloxacin (SPFX) against 10 isolates of Mycobacterium leprae were measured in the mouse foot pad system. The drugs were administered either by gavage or by incorporation into the mouse diet in a range of concentrations. The results demonstrated that the MEDs of OFLO were 4 to 5 times higher than those of SPFX, thus confirming that, on a weight-to-weight basis, the anti-M. leprae activity of SPFX was significantly greater than that of OFLO. The MEDs of OFLO/SPFX measured by gavage were 20 times lower than those measured by incorporating the drug into the mouse diet.

Animals↗
PubMed1995

Clarithromycin is inactive against Mycobacterium tuberculosis.

When 10% oleic acid-albumin-dextrose-catalase-enriched Mueller-Hinton agar medium was employed, the MICs of clarithromycin (CLARI) at which 50 and 90% of 12 strains of Mycobacterium tuberculosis were inhibited were 64 and > 128 micrograms/ml, respectively, which are significantly greater than the achievable peak CLARI concentrations in serum and in lung tissue in humans. In two different mouse experiments, 4 to 6 weeks of treatment with CLARI at 200 mg/kg of body weight six times weekly produced neither bactericidal nor bacteriostatic effects against M. tuberculosis. Therefore, we conclude that CLARI as a single drug is inactive against M. tuberculosis.

Animals↗
PubMed1995

Selection of clarithromycin-resistant Mycobacterium avium complex during combined therapy using the beige mouse model.

Sixteen weeks of treatment with clarithromycin (CLARI) alone displayed significant bactericidal activity against Mycobacterium avium complex infection in beige mice. Only two combined regimens, CLARI combined with an initial 4 or 8 weeks of amikacin (AMIKA), displayed activity greater than that displayed by CLARI alone. Four other combined regimens, CLARI combined with ethambutol (EMB), rifabutin (RBT), or both EMB and RBT during the entire 16 weeks of treatment or with AMIKA administered in an initial 2-week course showed bactericidal activity not significantly greater than that of CLARI alone. After 16 weeks of treatment, CLARI-resistant mutants were isolated from the majority of mice that had been treated with CLARI alone, CLARI-RBT, CLARI-EMB, or CLARI-EMB-RBT, as was the case for untreated controls, but the frequencies of occurrence of mutants were significantly greater in the groups treated with these combinations or CLARI alone. On the other hand, no CLARI-resistant mutants were isolated from the mice that had been treated with the combination of CLARI plus an initial 4 or 8 weeks of AMIKA and were isolated from only a tiny proportion of mice that had been treated with CLARI plus an initial 2 weeks of AMIKA. Therefore, only treatment with CLARI combined with an initial 4 or 8 weeks of AMIKA but not combined with RBT or EMB or both, could enhance the activity of the drug treatment and prevent the selection of CLARI-resistant mutants.

Amikacin↗
PubMed1995

Relapse after long-term follow up of multibacillary patients treated by WHO multidrug regimen. Marchoux Chemotherapy Study Group.

Thirty-five multibacillary (MB) leprosy patients were treated with 2 years of multidrug therapy (MDT) and followed up regularly for relapse. Relapse was defined as: a) an increase of the bacterial index (BI) by 2+ over the previous value from any single site of old lesions and b) the occurrence of definite new skin lesion(s) which demonstrated a higher BI than any pre-existing lesion. After a mean duration of 72.7 +/- 17.3 months of follow up per patient, seven relapses were diagnosed; the mean incubation period of relapse was 62.7 +/- 18.7 months. The overall relapse rate was 20.0% (or 3.3 per 100 patient-years), very significantly higher than the figures obtained from the same group of patients analyzed 2 1/2 years earlier, indicating that relapses occurred late (at least 5 +/- 2 years) after stopping MDT. Further analysis indicated that the relapse rate was closely correlated with the bacterial load of the patient, occurring far more frequently among patients with a BI of > or = 4.0 before MDT or with a BI of > or = 3.0 at the end of MDT. To avoid the alarmingly high relapse rate, it is proposed that the duration of MDT be doubled to 4 years in patients with an average BI of > or = 4.0 before MDT.

Adolescent↗
PubMed1994

Effectiveness of various antimicrobial agents against Mycobacterium avium complex in the beige mouse model.

The results of five chemotherapeutic experiments in beige mice infected with organisms of the Mycobacterium avium complex are presented. After monotherapy with various antimicrobial agents for 4 weeks, only clarithromycin, amikacin, and ethambutol displayed definite bactericidal effects; sparfloxacin and clofazimine showed modest bacteriostatic effects; and rifampin and rifabutin were totally inactive against the isolate tested. After treatment for 4 weeks, the large quantities of clofazimine that had accumulated in the organs of mice seriously interfered with the enumeration of the CFU and assessment of the efficacy of the treatment. The in vitro synergistic effects of drug combinations against M. avium complex were not confirmed in beige mice. In combination with clarithromycin, amikacin could prevent the selection of clarithromycin-resistant mutants, whereas minocycline could not.

Animals↗
PubMed1994

Clinical trial of ofloxacin alone and in combination with dapsone plus clofazimine for treatment of lepromatous leprosy.

Twenty-four patients with newly diagnosed lepromatous leprosy were allocated randomly to three groups and treated for 56 days with 400 mg of ofloxacin daily, 800 mg of ofloxacin daily, or 400 mg of ofloxacin, 100 mg of dapsone, and 50 mg of clofazimine daily plus 300 mg of clofazimine once every 28 days. The patients in all three groups demonstrated remarkable clinical improvements, accompanied by rapid decline of the morphological index in skin smears during treatment. More than 99, > 99.99, and > 99.99% of the viable Mycobacterium leprae organisms had been killed by 14, 28, and 56 days of treatment, respectively, as measured by inoculation into the footpads of immunocompetent and nude mice of organisms recovered from skin biopsy specimens obtained before and during treatment. Mild to moderate elevations of the serum glutamic pyruvic transaminase level were observed in four patients, all after 28 days of treatment, which returned to normal after the trial had been completed. Clinical improvement, bactericidal activity, and hepatotoxicity did not differ significantly among the three groups. Ofloxacin displayed powerful bactericidal activity against M. leprae in leprosy patients and may be an important component of new multidrug regimens for the treatment of leprosy. Its optimal dosage appears to be 400 mg daily, and combination with dapsone and clofazimine does not enhance its activity.

Adolescent↗
PubMed1994

Preventive therapy of tuberculosis with rifapentine in immunocompetent and nude mice.

The effectiveness of intermittent administration of rifapentine (RPT), with or without isoniazid (INH), for preventive therapy of tuberculosis was evaluated in immunocompetent (normal) and nude mice. After infection with a small inoculum of Mycobacterium tuberculosis H37Rv, normal mice developed a chronic and nonfatal infection, and the bacterial population became relatively stable after an initial period of limited multiplication. On the other hand, nude mice developed an acute and fatal infection, and all untreated mice died within 5 wk, with very high colony-forming-unit (CFU) counts in their organs. Various degrees of bactericidal activity were shown in normal mice after daily treatment with rifampin (RMP) plus pyrazinamide (PZA) for 13 wk, INH daily for 26 wk, or RPT once weekly for 13 or 26 wk or once fortnightly for 26 wk. The activity of RPT was significantly enhanced when INH was added at the same dosing frequency. In nude mice the response of M. tuberculosis infection to certain regimens was less favorable than that in normal mice, suggesting that preventive therapy may be less effective in severely immunodeficient hosts even during treatment. After chemotherapy was stopped, virtually all nude mice relapsed within 12 wk regardless of the regimen administered, whereas no or very few relapses were observed in normal mice that had been treated with RMP+PZA daily for 13 wk, or RPT alone or RPT+INH once weekly for 26 wk. The latter three regimens and RPT+INH once weekly for 13 wk may be applied for fixed-duration preventive therapy in human immunodeficiency virus (HIV)-negative subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Evaluation of an enzyme-linked immunosorbent assay that uses the 41-kd flagellin as the antigen for detection of antibodies to Borrelia burgdorferi in cattle.

An ELISA was developed to detect antibodies to the 41-kd flagellin (P41) of Borrelia burgdorferi in serum obtained from cattle. Absorption studies, immunoblot analysis, immunoelectron microscopy, and correlation of results of the P41-ELISA and the P39-ELISA as well as measurement of the antibody to P41 in calves challenge-exposed with Borrelia theileri were used to assess the specificity of the P41-ELISA. Antigens derived from Escherichia coli, Leptospira interrogans serovar hardjo, and B burgdorferi were used for absorption studies and immunoblot analysis. Antibodies to P41 of B burgdorferi cross-reacted with antigens of E coli, but were not cross-reactive with L hardjo. A value 3 SD higher than the mean of the negative-control population of cattle was defined as the minimum value (cutoff value) for a positive result by the P41-ELISA. Use of this value for classification of test results reduced the predicted rate of false-positive results attributable to E coli cross-reactivity to 1%. Immunoblot analysis revealed that test-positive serum from cattle reacted mainly with 41-, 39-, 34-, and 31-kd proteins of B burgdorferi, as well as several smaller proteins. Immunoelectron microscopy revealed that serum from cattle that was test-positive by the P41-ELISA bound to the flagellin and outer membrane of B burgdorferi. Results of absorption studies, immunoblot analysis, and immunoelectron microscopy were correlated and indicated that serum from cattle that was test-positive by P41-ELISA had stronger reactivity to B burgdorferi antigens than to antigens of E coli or L hardjo.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Seroepidemiologic survey of Borrelia burgdorferi exposure of dairy cattle in Wisconsin.

An ELISA, using purified flagellin of Borrelia burgdorferi as the solid-phase antigen, was used to measure antibody concentrations to B burgdorferi in dairy cattle in Wisconsin. Serum obtained from 5,060 cows in 160 randomly selected herds in the state were tested. Serum from an additional 2,600 cattle in Barron County, Wis, a county with a high annual incidence of B burgdorferi infections in human beings, was also tested. Only 7% of the cows that were tested, but 66% of the herds that were tested, were seropositive for B burgdorferi. Sixteen percent of the herds had a prevalence of > or = 15% seropositive cows, whereas 50% of the herds had a prevalence of 1 to 14% seropositive cows. Seropositive herds were concentrated in the west-central part of Wisconsin. An association existed between the geographic location of seropositive herds and counties in which B burgdorferi infection of human beings was acquired (P < 0.05) as well as the geographic location of seropositive herds and the geographic distribution of Ixodes scapularis (P < 0.05). Barron County, in which B burgdorferi infection is endemic, had a significantly (P < 0.05) higher percentage of seropositive cows (17%) than did the state of Wisconsin (7%).

Analysis of Variance↗
PubMed1994

[Dietary factors and cancer of the colon and rectum in a population based case-control study in Shanghai].

The study was a population-based case control one, to compare possible difference in the risk factors between colonic and rectal cancer. This study showed that: (1) High intake of pork and saturated fat was an important risk factor for colon cancer, and only slightly related to rectal cancer. (2) Low consumption of vegetables especially cruciferous vegetables, rhizome vegetables, sea weeds, legume vegetables, dietary fiber and some vitamins mainly derived from vegetables, e.g. vitamin c and carotene, was associated with an increased risk for both colonic and rectal cancer, and these factors were closer relationship with rectal cancer than colon cancer. (3) High intake of the fried and pickled foods significantly increase the risk of occurrence of these cancers. (4) The ratio of bowel cancer in first degree relatives of colon cancer cases was 2.9 times of control group (P < 0.01), but the ratio for rectal cancer was only 1.6 times (P > 0.05) compared with control group.

Adult↗
PubMed1994

[Comparison of risk factors between left and right-sided colon cancer].

To compare differences of risk factors between left-sided and right-sided colon cancer, a population-based comparative case-control study involving 267 patients with left colon cancer, 247 with right colon cancer and 1451 population controls matched by age (+/- 5 yrs) and sex was carried out in Shanghai. The major causes in the two cancer groups were dietary and nutritional factors. Vegetables, ascorbic acid, riboflavin, tocopherol and carotenes played a protective role in the two groups, but various other foods and some vitamins displayed different relations with the two types of cancer. A negative association was observed between dietary fiber and right colon cancer. Animal fat and some fatty acids (e.g. saturated fatty acids, mono-unsaturated fatty acids and oleic acid) significantly elevated the risk for left colon cancer, but only slightly for right colon cancer. Physical activity and familial history of colorectal cancer in first degree relatives showed a more remarkable relationship with left- than right-sided colon cancers.

Adult↗