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Biomedical subjects

H Bernhardt

Publications and source records attributed to H Bernhardt.

At least 19 recordsLinked to original sources

The first description of an oesophageal candidosis by Bernhard von Langenbeck in 1839.

In November 1839 the young university lecturer Bernhard (von) Langenbeck (1810-1887) published the first description of a fungus as aetiological agent of an oro-pharyngeal and oesophageal candidosis. We present his in English translated paper entitled 'Finding of fungi on the mucous membrane of the gullet of a typhoid fever corpse' (Germ.) in 'Neue Notizen aus dem Gebiete der Natur- und Heilkunde' (Froriep). There are interesting particulars in Langenbeck's description and discussion. The publication happened at the same time as that by Johann Lukas Schoenlein about fungi as the cause of the favus lesions. In this time Langenbeck lived at Göttingen. Later he went to Kiel and Berlin and became one of the most prominent surgeons of the 19th century. He sponsored the founding of the German Surgical Society, the Berlin Medical Society and the 'Archiv für Klinische Chirurgie'. In 1864 he was ennobled. Some of his assistants were Th. Billroth, R.U. Kroenlein, F. von Esmarch, and F. Trendelenburg.

Candidiasis↗

Candidosis and aspergillosis as autopsy findings from 1994 to 2003.

We analysed the autopsy records of the Greifswald University Institute of Pathology (located in Eastern Germany) in respect of findings of candidosis and aspergillosis from 1994 to 2003. We also present eight immature aborted fetuses and premature infants with a mycosis. In a total of 2027 autopsies we found 164 cases of invasive candidosis and aspergillosis (8.1%) including a combination of both on four occasions. Other authors cited between 0.7 and 7.3%. In these 10 years in our material mycoses and in particular candidosis increased in spite of slightly decreased numbers of autopsies. The differences comparing the 5-years periods (1994-98 and 1999-2003) are highly significant for both mycoses and candidosis. They are not significant for aspergillosis. A similar relationship was observed in the distribution of mycotic organs and causative origin for candidosis alone. In the last 5 years the gastrointestinal and respiratory tracts, including the peritoneum, were more frequently infected by Candida. Non-haematological neoplasia and pneumonia as basic diseases more often appeared in cases of candidosis. All eight immature aborted fetuses and premature infants suffered from candidosis. The survey confirms the importance of autopsy as a tool for education and quality control in medical diagnostic and therapeutic activity in the field of mycoses, too.

Aborted Fetus↗

Epidemiology of candidaemia in Europe: results of 28-month European Confederation of Medical Mycology (ECMM) hospital-based surveillance study.

In order to update the epidemiological and mycological profile of candidaemia in Europe, the European Confederation of Medical Mycology conducted a prospective, sequential, hospital population-based study from September 1997 to December 1999. A total of 2,089 cases were documented by 106 institutions in seven European countries. Rates of candidaemia ranging from 0.20 to 0.38 per 1,000 admissions were reported. Candida albicans was identified in 56% of cases. Non-albicans Candida species were most frequently isolated from patients with haematological malignancies (65%). With increasing age, an increasing incidence of Candida glabrata was seen. The 30-day mortality rate was 37.9%. The survey results underline the burden of candidaemia in a wide range of patient populations, confirm the importance of non- albicans species, and provide baseline data for future surveillance studies at a European level.

Adult↗

Influence of voriconazole and fluconazole on reconstituted multilayered oesophageal epithelium infected by Candida albicans.

Reconstituted multilayered oesophageal epithelium appears to be a good basis to test the efficacy of voriconazole (VOR) and fluconazole (FLU) in the tissue. The resulting model of a Candida oesophagitis was approaching the in vivo situation. We infected the tissue with 2 x 10(6) cfu of the Candida albicans strain SC5314. In the trials with FLU we also used clinical strains. Four hours after infection a good growth of C. albicans appeared mainly with hyphae on the surface of the tissue and a tendency to invasion. The destruction of the tissue began after 36 h. VOR (2 and 16 microg ml-1, respectively) prevented the penetration of hyphae into the tissue, when it was given 4-8 h after infection. It was less effective in reduction of Candida growth on the tissue surface. When VOR was given 16-24 h postinfection, the Candida infiltration stopped more slowly. Thirty-six hours after infection VOR application could not stop the destruction of the tissue despite reducing the fungi. The results with FLU (32 microg ml-1) were in principle the same, but not so distinct. FLU seems to be more effective against clinical strains of C. albicans than against the type strain.

Antifungal Agents↗

[Candida-specific antibodies in intensive care and non-intensive care patients].

The titres of indirect anti-Candida haemagglutination test (C-HAT) and specific immunoglobulins C-IgM, C-IgG and C-IgA in 328 intensive care (IT) patients and 166 non-intensive care (NIT) patients were compared by statistical test methods. Positive correlations were found between values of C-HAT and all three Candida-specific immunoglobulins. At an interval of < or =7 days in the first patient group only, the changes in the course of titres were statistically highly significant. For C-IgM the short-term increase of titres can be interpreted in the sense of happened mycotic infection in connection with the clinical picture. In IT patients we found an average increase of C-IgM at 259.3, C-IgG at 174.7, C-IgA at 59.8 U ml(-1) and of three titre steps in C-HAT. In our experience of diagnostics of Candida infections in intensive care area with non-neutropenic patients the short-term determination of the anti-Candida immunoglobulin subclasses C-IgM and C-IgG and of C-HAT as screening test should not be neglected.

Antibodies, Fungal↗

[Early signals of systemic mycoses--guidelines for therapeutic decisions?].

Clinical applications and in vitro studies show that all antimycotics are most effective against infection when applied as early as possible. An early diagnosis is, therefore, essential. At this time for aspergillosis and particularly candidosis, a statement is only possible by combining several diagnostic methods. Inflammatory parameters like procalcitonin, C-reactive protein and proinflammatory cytokines are most important evidence of infection. Antigen tests are more significant by higher sensitivity. Attention should be focused on the detection of mannan by ELISA test, beta-glucan and D-arabinitol. Given the present research level in the field of proteomics, the diagnostic importance of transmembranal receptor proteins or other regulatory proteins seems promising.

Antifungal Agents↗

Treatment of severe Candida infections in high-risk patients in Germany: consensus formed by a panel of interdisciplinary investigators.

Now that modern medicine can provide increasing chances of cure to patients with formerly incurable disorders, therapy-related complications play the key role in outcome. Thus, among opportunistic infections, severe candidiasis remains a challenge. A multidisciplinary panel of 20 investigators was formed to find a consensus on antifungal strategies for various underlying conditions in neutropenic and non-neutropenic patients. To record their preferences, the investigators used an anonymous voting system. Among antifungal agents, fluconazole emerged as the major alternative to the classic amphotericin B, being therapeutically at least equivalent but clearly less toxic. Factors that restrict the use of fluconazole include pretreatment with azoles, involvement of resistant species like Candida krusei, and an inability to exclude aspergillosis. Flucytosine can be reasonably combined with both amphotericin B and fluconazole. Within the limited antifungal armamentarium, amphotericin B lipid formulations and itraconazole also appear useful and require further investigation. The general consensus of the group is that antifungal agents should be administered at sufficient dosages, rather early, and often empirically.

Antifungal Agents↗

Funguria and Candida-specific immunoglobulins in patients with systemic candidosis.

UNLABELLED: Funguria, indirect anti-Candida haemagglutination test (C-IHT) and Candida-specific immunoglobulins C-IgM, C-IgG and C-IgA were investigated under suspicion of systemic candidosis in critically ill patients. A total of 143 urine cultures were studied for Candida from 74 adults and a median count of log 3.0 CFU ml-1 was found. Most isolated Candida species were Candida albicans and Candida glabrata. In 14 cases of candidaemia there was no regular agreement between the finding of Candida species in blood and urine. In cases with candiduria > = or log 3.0 CFU ml-1 a stronger increase of C-IHT titres and all three Candida-specific immunoglobulins after 5-7 days was observed. Some statistically significant correlations were found between the levels of urinary yeast counts and immunological parameters concerning C-IHT, C-IgA and C-IgG on the first day and after 5-7 days. Clinical findings in some cases coincided well with funguria and courses of titres before and after treatment. CONCLUSION: In critically ill patients suspected of having systemic candidosis not only blood cultures should be made. Cultural studies with specimens taken from different sites including funguria are essential for a complete specific serological investigation.

Aged↗

Oesophageal candidosis in intensive care patients.

We conducted upper intestinoscopies in 124 intensive care patients, six of whom had oesophageal candidosis. Of these, two also had Candida plaque in the stomach. The patients at the intensive care unit (ICU) had a mean Apache-II score of 26.7; whereas the score was 29.5 in patients with Candida oesophagitis. A significant increase of Candida antibodies was found in 59 of 124 patients (47.6%), including all patients with oesophageal candidosis. Presumably, mycotic infections of other sites were present. The severity by which mucous membranes were affected correlated well with microscopically evident invasiveness.

Candida↗

Fungal resistance.

Fungal resistance is caused by an acquisition of intrinsically resistant species, by selection of resistant strains from a population or by mutation of an initially susceptible strain. According to different classes of antimycotics there are different resistance mechanisms: differences in the uptake mechanisms, drug target alterations, mostly the ergosterol-biosynthesis pathway, and the efflux or pumping mechanisms to the outside.

Animals↗

[Difficulties of fungus detection in corneal culture medium].

UNLABELLED: It is not always possible to prevent the growth of microorganisms in organ culture for cornea preservation, despite many prophylactic measures. It is especially difficult to prove the presence of fungi in the cultural medium. MATERIALS AND METHODS: A culture medium was examined for sterility after 8 days' storage of cornea in organ culture. To prove the presence of fungi a culture of Sabouraud 2% glucose-agar was prepared and its growth examined by light microscopy. RESULTS: After 8 days of preservation we noticed a color change in the cultural medium and suspected contamination with fungi. Coagulase-negative Staphylococci could be cultivated from the conjunctival smear obtained before preparation of the cornea only. Routine screening of microbiological contamination did not show any results. We were able to identify an Aspergillus species only after preparing a special culture. The conjunctival smear as well as the cultural medium of the other eye of the same donor showed no contamination. CONCLUSIONS: In spite of the fact that microbiological contamination can be seen macroscopically, it is difficult to prove the presence of a specific microorganism and even more so when dealing with fungus. Especially in these cases the incubation of the cornea in media might have an advantage because contamination can be suspected by just looking at the medium. By excluding these preparations from transplantation we can possibly prevent infections, even when routine examinations show negative results.

Aspergillus↗

Candida albicans clinical isolates inactivated by formalin with different adherence to buccal epithelial cells induce proinflammatory and regulatory cytokines in human peripheral blood mononuclear cells.

Besides the activation of phagocytes, the release of cytokines is the most important immunological defence mechanism of an organism against infection with Candida albicans. On the other hand cytokines induced in the organism by the yeast itself are able to modulate the immune responses of the host. We investigated whether eight clinically isolated strains of C. albicans inactivated by formalin as well as a laboratory strain were able to induce proinflammatory and regulatory cytokines in peripheral blood mononuclear cells (PBMC) of four different donors. Under our assay conditions the yeast strains induced the cytokines interleukin-1 beta (IL-1 beta), interferon-gamma (IFN-gamma) and interleukin-10 (IL-10) in PBMC to varying extents, but not the cytokine interleukin-4 (IL-4). We observed a difference in the reaction of the individual donors to the stimulus C. albicans but on the other hand the extent of the cytokine signal seemed to be dependent on the yeast strain as well. No correlation was found between the ability of the individual C. albicans strains to induce cytokines in PBMC and their ability to adhere to buccal epithelial cells. Determination of the cytokine induction potential of C. albicans strains possibly may contribute to the detection of new virulence factors of this yeast.

Candida albicans↗

The continuous flow culture as an in vitro model in experimental mycology.

We used the model of continuous flow culture (cfc) to study the growth of Candida species. This model allows special test conditions: a long generation time of 15-20 hs, controlled limitation of nitrogen sources and carbohydrates, comparison of the growth under aerobic and anaerobic conditions simultaneously. These conditions were used to study the effect of antimycotic drugs, mainly during a long time of 7 to 10 days. Germ tube formation as a virulence factor was more abundant and faster in cfc of strains with a stronger adherence to buccal epithelium cells. Co-cultivation of C. albicans and C. glabrata allowed conclusions for their colonization in vivo. A biofilm on the glass wall of the culture vessel led to mycelium formation by C. albicans. Concomitantly the growth of C. glabrata was favoured. Growth of C. albicans in the gastrointestinal flora was reduced by masses of bacteria and their multiple metabolic activities. A remarkable growth of C. albicans was only to be seen if the ecosystem was destroyed e.g. by antibacterial antibiotics. The influence of fluconazole in a long-term follow up study under anaerobic conditions showed an inhibition of C. albicans in 99.9%. This means fungicidal efficacy.

Candida↗

Influence of ciprofloxacin and other antimicrobial drugs on different Escherichia coli strains in continuous-flow cultures under aerobic and anaerobic conditions.

In continuous-flow culture, long generation times and high bacterial counts favour survival of bacteria. A chemotherapeutic agent that achieves a bactericidal effect under these circumstances can therefore be seen as highly effective. In our continuous-flow culture we obtained bactericidal effects with ciprofloxacin 1-2 mg/L, cefotaxime 4 mg/L and mezlocillin 32 mg/L. These effects were seen irrespective of whether conditions were aerobic or anaerobic. There were no significant differences between monocultures and mixed cultures simulating faecal flora with the various Escherichia coli strains tested. Cefotaxime had an initial effect but an increase in counts was then observed as a result of regrowth of E. coli survivor strains in aerobic monoculture and mixed cultures. Mezlocillin was completely bactericidal in monocultures, but regrowth occurred in mixed cultures under anaerobic conditions. Neither the bacterial composition of this culture nor the resistance pattern explained this regrowth. These results were observed in long-term experiments followed for up to 7 days. We conclude that the antibiotics tested are highly effective against E. coli under unfavourable conditions simulating in-vivo situations.

Aerobiosis↗

[Fungi in the intestine--normal flora or pathogens?].

Candida spp. und C. albicans are common within the microbial ecosystem of the human orointestinal tract. Candida in low quantities is found at various sites in healthy subjects. In patients with typical risk factors, mainly in immunocompromised hosts, an increased growth of Candida occurs. In cases with multiple sites colonised there will be an increased risk of severe Candida infections. The metabolic activity of Candida in the gut is very low under anaerobic condition and limitation of nutrients.

Candida↗

Mycological aspects of gastrointestinal microflora.

There are two aspects about the presence of Candida in the human orointestinal tract: (i) it is a part of normal human flora and (ii) it is a risk factor for immunocompromised patients. The orointestinal tract can be considered a reservoir for Candida species, several of which are from the oral cavity, stomach, duodenal juice and faeces. Their germ counts in normal small and large bowel do not exceed 10(4) cfu/ml resp.g. The input of Candida to a well-developed faecal flora system under continuous flow culture conditions did not lead to a multiplication of the yeast. The take in of faecal flora into a Candida continuous flow culture diminish Candida germ counts. If, however, the faecal flora was destroyed, e.g. by antibiotics, we found the yeasts multiplying, with the formation of germ tubes and mycelial structures. Colonization by Candida has to be seen as a starting-point of the development of subsequent candidosis in immunosuppressed or intensive care patients. The best protection against Candida colonization in the gut is the existence of a normal bacterial flora. Lactulose, which promotes the Gram-positive potential of faecal flora, may protect indirectly by supporting the indigenous flora.

Adult↗

Dynamics of Candida isolations from humans from 1992-1995 in Greifswald, Germany.

In the period 1992-95 there was a significant shift in the spectrum of Candida species in the University Hospital in Greifswald. During this time, the annual number of specimens taken for mycological investigations of adults increased threefold (total n = 11,568). The isolation rate of Candida species was 50.5%. The percentage of C. albicans isolates decreased from 76% to 54.4% with the lowest level in 1994. The opposite trend in the occurrence of non-C. albicans species was seen, for example the occurrence of C. glabrata, from 11.7% to 28.4%. We found only 98 strains of C. parapsilosis (1.4%) during the 4 years. The occurrence of Candida species in a variety of habitats was different. During the 4 years, the same annual percentages of C. albicans (mean 87.9%) were isolated from endoscopic oesophageal smears, whereas the distribution of Candida yeasts from the oral cavity, the respiratory tract, faeces and urine had changed. Over the years, at these locations, C. albicans was less frequently isolated and non-C. albicans species clearly increased. The highest occurrence of C. glabrata was found in urine, in which the isolation percentage almost doubled from 23.1% to 40.9% in 1994. In contrast to adults, in all specimens originating from a paediatric clinic that included neonatology the occurrence of C. albicans was high (83.5% in 1995), but the isolation rate of Candida species was low (12.3%). These results are important because of the differences in yeast susceptibility, of non-C. albicans species in particular, against antifungal drugs.

Adult↗