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Biomedical subjects

W Brehmer

Publications and source records attributed to W Brehmer.

11 recordsLinked to original sources

[Clinical aspects and pathology of mycobacterial infections in AIDS. Pulmonary and extrapulmonary manifestations].

Infections with M. tuberculosis and other mycobacteria (atypical mycobacteria) are frequently found in patients with AIDS. They are almost always disseminated, and are associated with a spectrum of findings that is often unhelpful for the diagnosis. In the case of tuberculosis, typical granulomas are a major finding. The histological correlate of mycobacteriosis is histiocytosis; granulomas are rarely observed, and when they do present, are incompletely developed.

Acquired Immunodeficiency Syndrome

[Resistance testing of M. avium-intracellulare and M. tuberculosis of AIDS patients with new drugs and drug combinations].

The minimal inhibitory concentration (MIC) of rifabutin for M. tuberculosis was 0.006 to 0.06 micrograms/ml, and 0.12 to 0.25 micrograms/l for clofazimine. Accordingly, M. tuberculosis is inhibited by concentrations of these two medications that are far lower than the levels normally found in the serum. In the case of M. avium, the MIC of the new drugs such as rifabutin and clofazimine are, in contrast to the MICs for M. tuberculosis, merely of the order of the achievable serum concentrations. The minimum bactericidal concentrations of these two substances are much higher than the bacteriostatic concentrations, which probably explains the frequent therapeutic failures, while in the case of ciprofloxacin, the prevailing situation is much more favourable. The growth of all M. avium strains is inhibited (= sensitive) when elevated concentrations (double "breakpoint" concentrations) of a triple-drug combination comprising rifampicin, ethambutol and ciprofloxacin, or a combination of ethambutol, rifampicin, ciprofloxacin and prothionamid are tested at "normal breakpoint" concentrations.

Acquired Immunodeficiency Syndrome

The effect of Toxoplasma cell fractions and mycobacterial immunostimulants against virulent Toxoplasma gondii in mice.

Toxoplasma gondii tachyzoites were disrupted in a Ribi cell fractionator and separated into cell walls and protoplasm by differential centrifugation. These products were used alone or combined with a mycobacterial glycolipid (P3) and injected either as oil-in-water emulsions or incorporated in Freund's incomplete adjuvant. Mice were vaccinated by intravenous or intradermal routes and challenged intraperitoneally with a highly virulent strain of Toxoplasma gondii. A local granuloma formation was induced after i.d. inoculation of Toxoplasma vaccines containing P3 as this glycolipid enabled an adherence of the antigens on the mineral oil droplets. The adjuvant effect of P3 on antibody formation was also observed. Most of the fractions showed a low, but statistically significant prolongation of survival time. Vaccination by the i.v. route with homologous or heterologous antigens, including Trypanosoma cruzi, were not significantly effective, with the exception of a high dose of Toxoplasma protoplasm associated with P3.

Adjuvants, Immunologic

[Immunotherapy with BCG and mycobacterial fractions and its use in bronchogenic carcinoma (author's transl)].

Animal experiments at the Nat. Cancer Inst. have established that only intra-tumorous application of BCG vaccine has a lasting immunotherapeutic effect on transplantable tumours. However, clinical observations have proved that BCG immunotherapy by the intra-tumorous route increases the incidence of complications, such as allergic reactions and generalized spread of BCG, to an unacceptable level. Ribi has produced a vaccine from mycobacterial fractions which is low in protein and which, as proved in clinical pilot studies in cases of melanoma and cancer of the breast, is so well tolerated that it can be injected into the tumour. Since bronchogenic carcinoma is in the majority of cases inoperable, but, on the other hand, can be reached directly via the bronchoscope or the perthoracic route a pilot study with the Ribi vaccine was started in patients with lung cancer. The preliminary results are reported.

BCG Vaccine

[Regional suppurative lymphadenitis after BCG vaccination (author's transl)].

In the first half of 1975 there occurred in the Federal Republic of Germany an unusual rise in the incidence of suppurative inguinal lymphadenitis after BCG vaccination of newborns, in immediate time relation with change of the vaccine by its manufacturers, Behringwerke. The attenuated daughter strain Göteborg had been replaced by the effective but also rather aggressive strain Copenhagen 1331. The complication rate was 1.5% in West Berlin. Clinical course, operative technique as well as microbiological and histomorphological features of these cases were analyzed in a joint study. Since it is likely that, after re-admission of the Copenhagen vaccine, such complications may again occur despite reduced micro-organism count, vaccination of newborns should in future be restricted to those at risk.

BCG Vaccine

Immunotherapy with nonviable microbial components.

Structural components of microorganisms have been studied for immunopotentiating effect with the aid of transplantable (line 10) tumors in syngeneic guinea pigs. Microbial components were associated with oil droplets, suspended in Tween-saline, and injected intralesionally. BCG cell walls, given in this way, produced regression and cure of 50-60% of established tumors, as did viable BCG. Lipid extraction markedly reduced the tumor-regressing potency of cell walls, but P3, a trehalose mycolate present in the extract, restored full activity to the cell wall residue. P3 alone was nonsensitizing and had no antitumor activity, but it enhanced the latter property of various other microbial products. For example, the cure rates produced by cell walls of M. tuberculosis, M. bovis, M. phlei, or M. smegmatis were enhanced from 20-60% to as much as 90% by addition of P3. P3 also conferred antitumor activity on products from unrelated microbes, such as cell walls of E. coli, and in combination with endotoxins from rough Re mutant salmonellae, it produced cure rates of up to 93%. These results suggest that P3 is essential to the immunopotentiating activity of mycobacteria and that it may be broadly applicable in immunotherapy of cancer with microbial agents.

Animals

Cutaneous granulomatous response to BCG cell walls with reference to cancer immunotherapy.

A chronic inflammatory response produced by cell walls of Mycobacterium bovis strain BCG associated with microscopic oil droplets (BCG CW-O) was studied with reference to the tumor-regressing ability of this preparation. When BCG CW-O was injected intradermally in the footpads of guinea pigs, intense inflammation developed at the site of injection and in the draining popliteal lymph node. This was characterized histologically as granulomatous inflammation. The intensity of the response was related to the dose of BCG CW-O. Cell walls without oil produced the same type of inflammation but much less in degree. Data are presented that demonstrate the immunological nature of this response and classify it as a cell-mediated immune reaction. Ramifications of this chronic inflammatory reaction occurring at the site of a tumor are discussed.

Animals

[Fatal course of generalized BCG histiocytosis in congenital immune deficiency (author's transl)].

Severe combined X-linked immune deficiency ended fatally in a six-month-old male infant after generalized BCG infection. Damage in the cell-bound thymus-dependent immune system is decisive in the development of "BCG histiocytosis". As a result of absent immunocompetent sensitized T-lymphocytes there is insufficient information and stimulation of macrophages to kill the micro-organsims. The disorder of bactericidal properties of macrophages results in an overwhelming infection with BCG bacteria with a characteristic morphological picture.

BCG Vaccine