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Biomedical subjects

M Ruhnke

Publications and source records attributed to M Ruhnke.

At least 19 recordsLinked to original sources

Highly active antiretroviral therapy (HAART) improves survival in HIV-associated Hodgkin's disease: results of a multicenter study.

BACKGROUND: The purpose of the study was to evaluate the outcome of Hodgkin's disease (HD) in patients infected with the human immunodeficiency virus (HIV) with respect to the use of highly active antiretroviral therapy (HAART). MATERIALS AND METHODS: This cohort study included patients with HIV-HD diagnosed from June 1984 to February 2004. Patients treated in the pre-HAART era (1984-1996) were compared with those belonging to the HAART era (1997-2004). RESULTS: Of 66 patients with HIV-HD, 47 (71%) presented with stage III/IV disease and 38 patients (58%) with an AIDS-defining illness. Fifty-nine of 66 patients (89.4%) underwent curative intended chemotherapy. Patients receiving HAART (n = 34) had a significantly better 2-year overall survival (OS) than those not receiving HAART (74% versus 30%, P <0.001). The 2-year OS of HAART-responders was 88% compared with 19% in patients without HAART-response (P = 0.0002). By multivariate analysis patients without HAART had a 5.6-fold higher risk for 3-year mortality [HR 5.6, 95% confidence interval (CI) 2.20-14.26]. Three-year mortality was significantly higher in patients without complete remission (HR 4.40, CI 1.77-10.99), with stage III/IV HD (HR 4.64, CI 1.31-16.49) and with CD4 cells <200/microl (HR 2.69, CI 0.99-7.33). CONCLUSIONS: Use of HAART significantly improved the overall survival in patients with HIV-HD.

Acquired Immunodeficiency Syndrome↗

Multipotent cells of monocytic origin improve damaged heart function.

Recently, we generated cells with multipotent properties from blood monocytes that in vitro differentiate into various somatic cell types. This experimental study investigated whether these programmable cells of monocytic origin (PCMO) succeed to restore left ventricular function after myocardial infarction (MI). PCMO were generated from monocytes by exposition to RPMI medium containing M-CSF and IL-3 for 6 days. MI was induced in female Lewis rats ligating the left coronary artery. PCMO of male Lewis donors were injected either intramyocardially (i.my.) or intravenously (i.v.) 24 h or 6 days post-infarction. Hemodynamic assessment after 60 days demonstrated significant improvement of left ventricular function following i.my. transplantation of PCMO as well as early (24 h post-infarction) i.v. application while nonmodulated monocytes failed to restore heart function. The Y-chromosome-specific SRY gene of male donor PCMO was detected exclusively in infarcted hearts of animals, which demonstrated improved cardiac function. Subdivision of infarcted hearts by microdissection localized the SRY gene-containing department to the left ventricle adjacent to the infarcted area whereas the right ventricle remained negative. Successful generation of PCMO in access numbers allows their autologous use as a new additive treatment for early restoration of cardiac function after MI.

Animals↗

Unusual enhancement pattern of liver lesions in hepatosplenic candidiasis.

PURPOSE: To describe an unusual enhancement pattern of hepatosplenic candidiasis (HSC) liver lesions in biphasic spiral liver computed tomography (CT). MATERIAL AND METHODS: Twenty-one patients with suspected HSC were scanned with a biphasic liver CT perfusion protocol. The liver lesions detected were assessed for their morphology and enhancement pattern during both perfusion phases. A liver biopsy was performed in 11/21 patients. RESULTS: The majority of hepatic lesions in 15/21 patients showed the well-known abscess-like pattern. In 6/21 patients an uncommon central contrast enhancement with a peripheral double ring was detected in the arterial phase. In some cases the lesions showed decreased diameter or even seemed to disappear completely in the portalvenous phase. CONCLUSIONS: CT in the arterial phase showed an unusual enhancement pattern of liver lesions in HSC. Scanning only in the portalvenous phase implies possible pitfalls, because lesions may be overlooked or undersized. Therefore, biphasic liver CT is considered essential in the diagnosis and follow-up of HSC in clinical practice.

Adult↗

Update on antifungal treatment of invasive Candida and Aspergillus infections.

Invasive Candida and Aspergillus infections are among the most common serious complications occurring in chronically immunosuppressed patients, in particular those with hematological malignancies and transplant recipients. A rational, early systemic antifungal treatment can be based upon imaging diagnostic techniques as well as upon conventional mycological and non-culture-based procedures. The availability of well tolerable and highly efficacious systemic antifungals has improved the spectrum of therapeutic options and the success rates of antifungal treatment. However, with respect to high treatment costs associated with these new agents, it is mandatory to specify indications and limitations for the use of these substances. Voriconazole may well become the new standard primary treatment of invasive aspergillosis. The role of the new echinocandins such as caspofungin, which has recently been approved for salvage treatment of resistant and refractory Aspergillus infections, in primary or combination treatment of invasive aspergillosis must be further studied. Caspofungin is at least as effective as, yet significantly better tolerated than amphotericin B for primary treatment of invasive candidosis in non-neutropenic patients, and has been approved for this indication. The selection of systemic antifungals in patients with invasive Candida infection critically depends upon the identification of Candida species involved, because some non-albicans Candida spp. are resistant to azole antifungals.

Antifungal Agents↗

Diagnosis of invasive fungal infections in hematology and oncology--guidelines of the Infectious Diseases Working Party (AGIHO) of the German Society of Hematology and Oncology (DGHO).

Invasive fungal infections are a primary cause of morbidity and mortality in patients with hematological malignancies. Establishing a definite diagnosis of invasive fungal infection in febrile neutropenic patients is particularly challenging and time-consuming, but a delay of antifungal treatment leads to higher mortality. This situation has lead to the strategy of initiation "empirical" antifungal therapy prior to the detection of fungi. Meanwhile, improvements in diagnostic procedures are achieved, especially with imaging techniques and non-culture based methods which include antigen-based assays, metabolite detection and molecular detection of fungal DNA from body fluid samples using conserved or specific genome sequences. The AGIHO presents recommendations for the diagnosis of invasive fungal infections with risk-adapted screening concepts for the neutropenic and febrile episodes of patients with hemato-oncological disorders.

Hematology↗

Antimicrobial therapy of unexplained fever in neutropenic patients--guidelines of the Infectious Diseases Working Party (AGIHO) of the German Society of Hematology and Oncology (DGHO), Study Group Interventional Therapy of Unexplained Fever, Arbeitsgemeinschaft Supportivmassnahmen in der Onkologie (ASO) of the Deutsche Krebsgesellschaft (DKG-German Cancer Society).

Cytostatic chemotherapy of hematological malignancies is often complicated by neutropenia, which increases the risk of infections, especially if the neutrophil count is below 500/microl. Frequently, fever is the first, and in most patients the only, sign of an infection. Unexplained fever is defined as follows: temperature of >/=38.3 degrees C or >/=38.0 degrees C for at least 1 h, or measured twice within 12 h, if the neutrophil count is <500/microl or <1000/microl with predicted decline to 500/microl. Different risk categories can be identified according to the duration of neutropenia: low risk </=5 days, intermediate risk 6-9 days, high risk >/=10 days. An empirical mono- or duotherapy with antipseudomonal and antistreptococcal agents should be initiated immediately. In the low risk patient group, oral therapy with cipro-, levo-, or ofloxacin combined with amoxicillin/clavulanic acid is permissible. For standard and high risk patients, monotherapy can be carried out with either ceftazidime, cefepime, piperacillin with tazobactam or a carbapenem. In duotherapy, a single dose of an aminoglycoside is combined with acylaminopenicillin or a cephalosporin of the third or fourth generation. The addition of glycopeptides in empirical therapy should only be considered in the presence of severe mucositis, or if a catheter-associated infection is suspected. If fever persists after 72-96 h of first-line therapy with antibiotics, the regimen should be modified (with the exception of e.g. coagulase-negative staphylococci infections, because these infections take longer to respond). Intermediate risk patients should additionally receive an aminoglycoside after monotherapy (penicillin or a cephalosporin). If a carbapenem was administered for monotherapy, this can be followed by a quinolone and/or a glycopeptide. In the high risk group, the same modifications should be made as in the intermediate risk group but with additional systemic antifungal treatment. In the presence of unexplained fever, fluconazole can be administered at first, but if this fails, amphotericin B (conventional or liposomal), itraconazole, voriconazole or caspofungin should be started. After defervescence to <38 degrees C, treatment should be continued for 7 days if the neutrophil count is <1000/microl, and for 2 days if the neutrophil count is >1000/microl.

Anti-Bacterial 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↗

[Voriconazole - applications and perspectives].

Voriconazole (Vfend) is a new broadspectrum antifungal agent belonging to the group of triazole drugs. In vitro and in vivo efficacy was demonstrated against a large variety of yeasts with excellent activity against all Candida species but as well against Cryptococcus neoformans. Furthermore, voriconazole has shown excellent activity against many moulds in particular against Aspergillus species, but endemic fungi such as Histoplasma capsulatum are in the spectrum as well. Clinical efficacy was demonstrated in several large phase II/III studies in diseases such as oral and oesophageal candidosis, acute invasive aspergillosis or chronic invasive aspergillosis. New adverse events such as visual disturbancies has been described together with the use of voriconazole, but the majority of adverse events are similar to other triazole drugs and in particular not life-threatening. With the introduction of voriconazole a great progress in the therapy of invasive fungal infections was achieved. In the therapy of invasive aspergillosis, voriconazole is significantly more effective compared to amphotericin B desoxycholate.

Antifungal Agents↗

Tap water colonization with Pseudomonas aeruginosa in a surgical intensive care unit (ICU) and relation to Pseudomonas infections of ICU patients.

Water faucets on a surgical intensive care ward were examined prospectively as a source of Pseudomonas aeruginosa infections. All water outlets harbored distinct genotypes of P aeruginosa over prolonged time periods. Over a period of 7 months, 5 (29%) of 17 patients were infected with P aeruginosa genotypes also detectable in tap water.

Cross Infection↗

Regression of Epstein-Barr virus-associated lymphoproliferative disorders in patients with acquired immunodeficiency syndrome during therapy with foscarnet.

Epstein-Barr virus (EBV)-associated lymphoproliferative disorders frequently develop in patients with acquired immunodeficiency syndrome (AIDS). The lymphoproliferative disorders are usually treated with a combination of cytotoxic drugs, and virustatic medication is thought to be ineffective. However, we report about two AIDS patients with EBV-associated lymphoproliferative disorders not responding to a standard chemotherapy, who achieved complete tumour regression after virustatic therapy with foscarnet.

Acquired Immunodeficiency Syndrome↗

[Invasive Candida infection in surgical patients: a valid clinical entity].

OBJECTIVE: Establishment of a case definition for invasive candidosis in postsurgical intensive care patients. METHODS: During the period of 1996-1999, 8 cases of invasive candidosis were observed on a surgical intensive care unit. Patient records were evaluated with respect to diagnostic criteria and response to antimycotic therapy. RESULTS: Patients included 3 women and 5 men with a mean age of 62.7 (37-85) years. Candida peritonitis (n = 6) occurred after surgery or perforation of the intestinal tract, and Candida pneumonia was due to artificial ventilation (n = 3). C. albicans was isolated in all 8 cases, but mixed infections with other Candida spp. occurred in 3 cases. The Candida serum antigen test yielded a positive result in only 2/8 cases. I.v. therapy with fluconazole was successful in 7 cases, one patient with severe initial disease died with ongoing infection. With the exception of the lethal case, all patients showed a diagnostic serum antibody test, proving systemic candida infection. CONCLUSION: Based on the case descriptions, we propose the following definition of invasive candidosis: (1) Clinical signs of infection after surgery, (2) absence of bacterial pathogens and/or failure to respond to systemic antibiotics, (3) cultivation of Candida spp. from normally sterile sites or abundant growth in tracheal aspirate, (4) response to antimycotic therapy and (5) diagnostic serum antibody test. This definition proved to be valid for our patients and could be used as an inclusion criterion for future clinical studies of serodiagnosis of Candida infection or antimycotic chemotherapy.

Adult↗

Development of simultaneous resistance to fluconazole in Candida albicans and Candida dubliniensis in a patient with AIDS.

In this report, we describe a patient with recurrent episodes of oral candidosis who finally suffered from fluconazole-refractory oral and oesophageal candidosis. The patient was monitored for 4 years until his death from AIDS. During the observation period, persistent colonization with both Candida albicans and Candida dubliniensis was observed. From the appearance of the first episode of oral candidosis, the patient was treated with fluconazole for 18 months. The infection became unresponsive to fluconazole 400 mg/day. In vitro susceptibility testing revealed the development of resistance to fluconazole in C. albicans and C. dubliniensis. Molecular typing confirmed the persistence of the same C. albicans and C. dubliniensis strains which developed resistance after up to 3 years of asymptomatic colonization. This observation demonstrates that Candida spp. other than C. albicans may develop resistance to fluconazole in a patient who is repeatedly exposed to the drug.

Acquired Immunodeficiency Syndrome↗