[A German version of the Cambridge examination for mental disorders of older people with Down's syndrome and others with intellectual disabilities : A diagnostic procedure for detecting dementia in people with Down's syndrome]. / Eine deutsche Fassung der Cambridge Examination for Mental Disorders of Older People with Down's Syndrome and Others with Intellectual Disabilities : Ein Diagnoseverfahren zur Erfassung von Demenz bei Menschen mit einem Down-Syndrom.

BACKGROUND: Although people with Down's syndrome (DS) are at a high risk of developing an Alzheimer type dementia (AD) due to a triplication of the amyloid precursor gene, there are practically no internationally available test procedures to detect cognitive deficits in this at risk population in the German language. OBJECTIVE: The aim was to provide a German translation and intercultural adaptation of the Cambridge examination for mental disorders of older people with Down's syndrome and others with intellectual disabilities (CAMDEX-DS), which is available in English and Spanish. This instrument for diagnostics and monitoring consists of a psychological test examination (CAMCOG-DS) and a caregiver interview. METHODS: The translation and adaptation of the CAMDEX-DS were achieved through a multistep translation process, whereby two independent forward and back translations were provided by professional translators and a consensus version was finalized and tested. The final version of the caregiver interview was applied to 11 subjects and the CAMCOG-DS was conducted with 28 patients. RESULTS: The German version of the CAMDEX-DS proved to be easily administered. The CAMCOG-DS could be fully administered to 21 out of 28 patients (75%). The CAMCOG-DS values were much lower for older patients aged ≥45 years than for younger patients (46/109 vs. 73.5/109; p = 0.033). DISCUSSION: The German version of the CAMDEX-DS provides an internationally recognized tool for the diagnostics and monitoring of cognitive decline in Down's syndrome. Furthermore, the German version can standardize medical care of these patients. In particular it provides a means of participation in international research trials for this at risk population.

Decision making at the end of life--cancer patients' and their caregivers' views on artificial nutrition and hydration.

PURPOSE: Deciding on artificial nutrition and hydration (ANH) at the end of life (EoL) may cause concerns in patients and their family caregivers but there is scarce evidence regarding their preferences. Therefore, the aim of this study was to assess the impact of factors associated with ANH decision making. METHODS: Prospective, Cross-sectional survey. Adult patients admitted to hospital for symptoms of advanced cancer as well as their family caregivers completed a self-administered questionnaire. Items included personal views and concerns about ANH. Family caregivers additionally recorded their preference for their loved one and, if applicable, previous experience with ANH decisions. RESULTS: Thirty-nine out of sixty-five patients and 30/72 relatives responded. Higher age of the patient was significantly correlated with both the patient's and the relative's decision to forgo ANH (Kruskal-Wallis test, p < 0.01). Thirty-nine percent of patients, 37 % of relatives if deciding for themselves, and 24 % of relatives if deciding on behalf of their loved one opted against ANH; 36, 40 and 52 % preferred artificial hydration (AH) only (χ (2) test, p <0.001), while 23, 23 and 24 %, respectively, wished to receive ANH. Patients felt more confident about decisions on artificial nutrition (AN) than caregivers (T test, p < 0.05) and less concerned about adverse effects of forgoing ANH on pain, agitation and sensation of hunger and thirst (χ (2) test, p < 0.05). Satisfaction of patients with communication regarding forgoing ANH (5.0 ± 2.8 on a Likert scale from 0 to 10) correlated with their confidence (Spearman's rho, p < 0.01). A thorough consultation with the attending physician on ANH issues was the favoured source of support for 77 % of patients and 97 % of relatives. A majority of patients considered their relatives' opinion (67 %) and their own advance directives (62 %) as crucial for making ANH decisions, and 46 % of them had such a document completed. CONCLUSION: Cancer patients and their relatives have similar preferences regarding ANH at the EoL, but relatives are reluctant to withhold AH if deciding for their loved one. While patients seem to be confident with ANH decision making, their caregivers may particularly benefit from discussing ANH options to dissipate fears.

[Drug therapy of anxiety and fear in palliative care patients with cancer or other illnesses : a systematic review]. / Medikamentöse therapie der angst bei patienten mit fortgeschrittenen tumorerkrankungen bzw. Patienten in der palliativen situation : systematische literaturübersicht.

BACKGROUND: Pharmacological treatment of anxiety is an important part of drug treatment in palliative care. In this review we searched for the current evidence of pharmacological treatment of anxiety in palliative care. MATERIALS AND METHODS: A systematic search of PubMed, Embase, PsycLIT, PsycINFO, CINAHL for studies of anxiety in palliative care was carried out in January 2012. Furthermore we searched the Cochrane Library, references of literature and leading textbooks. Studies were identified and information was filled in a standardized extraction sheet. Studies have been categorized and anxiety as an endpoint determined. RESULTS: A total of four controlled studies, three uncontrolled studies, two retrospective studies, one case report, two surveys, one systematic Cochrane review and one unsystematic review were analyzed and included in this review. This indicates an overall low number of studies for the pharmacological treatment of anxiety in palliative care. According to our results, benzodiazepines are the most commonly used drugs in palliative care. However, based on our review, there is no evidence-based recommendation for the therapeutic use in palliative care. CONCLUSIONS: With the existing evidence no general recommendations for pharmacological treatment of anxiety in palliative care can be given. Even for the commonly used benzodiazepines, neuroleptics, antidepressants, antihistamines and beta blockers for the treatment of anxiety no evidence based recommendations can be made. However, these medications are commonly used to treat anxiety in other patient populations and can also be used in palliative care patients. According to our review we cannot recommend a single drug or give recommendations regarding the dosage of drugs. There is a strong need for randomized controlled trials to evaluate the effect of drug treatment of anxiety in palliative care patients. The English full text version of this article will be available in SpringerLink as of November 2012 (under "Supplemental").

A review of German Scedosporium prolificans cases from 1993 to 2007.

Scedosporium prolificans is one of the most life-threatening fungal opportunistic pathogens due to its high resistance to common systemic antifungal agents. While a close relative of Pseudallescheria boydii, S. prolificans has a more limited geographic range being primarily found in Australia, USA and Spain. Infections have also been reported from several other European countries and from Chile. Twenty patients with Scedosporium prolificans infection or colonization from August 1993 to May 2007 were retrospectively reviewed in Germany. They had all been identified at or reported to the Reference Laboratory for Pseudallescheria/Scedosporium spp. in Berlin. Twelve of 13 patients with haematological disorders and/or on immunosuppressive therapy developed a fatal invasive scedosporiosis. Colonization of the respiratory tract was reported for one patient after heart-lung-transplantation, all six patients with cystic fibrosis and one with chronic sinusitis. Molecular studies of the S. prolificans isolates confirmed that parts of the 18S, the Internal Transcribed Spacer (ITS) regions and the D1/D2 domain of the 28S region of rDNA are monomorphic. However, sequencing of parts of the translation elongation factor EF1-alpha (EF-1alpha) and the chitin synthase (CHS-1) genes revealed the presence of three and two distinct genotypes, respectively. Two informative mutations were found in EF-1alpha and a single nucleotide exchange in the CHS-1 gene.

European cluster of imported falciparum malaria from Gambia.

A cluster of 56 patients returning from Gambia with falciparum malaria has been noted in several countries of the European Union since September this year. TropNetEurop, the European Network on Imported Infectious Disease Surveillance, collected and reported the cases. Lack of awareness and, consequently, of prophylactic measures against malaria were apparent in the majority of patients.

PCR based identification and discrimination of agents of mucormycosis and aspergillosis in paraffin wax embedded tissue.

BACKGROUND: Invasive fungal infections are often diagnosed by histopathology without identification of the causative fungi, which show significantly different antifungal susceptibilities. AIMS: To establish and evaluate a system of two seminested polymerase chain reaction (PCR) assays to identify and discriminate between agents of aspergillosis and mucormycosis in paraffin wax embedded tissue samples. METHODS: DNA of 52 blinded samples from five different centres was extracted and used as a template in two PCR assays targeting the mitochondrial aspergillosis DNA and the 18S ribosomal DNA of zygomycetes. RESULTS: Specific fungal DNA was identified in 27 of 44 samples in accordance with a histopathological diagnosis of zygomycosis or aspergillosis, respectively. Aspergillus fumigatus DNA was amplified from one specimen of zygomycosis (diagnosed by histopathology). In four of 16 PCR negative samples no human DNA was amplified, possibly as a result of the destruction of DNA before paraffin wax embedding. In addition, eight samples from clinically suspected fungal infections (without histopathological proof) were examined. The two PCR assays detected a concomitant infection with Absidia corymbifera and A fumigatus in one, and infections with Rhizopus arrhizus and A fumigatus in another two cases. CONCLUSIONS: The two seminested PCR assays described here can support a histopathological diagnosis of mucormycosis or aspergillosis, and can identify the infective agent, thereby optimising antifungal treatment.

An unusual case of Aspergillus endocarditis in a kidney transplant recipient.

The incidence of aspergillosis in kidney transplant recipients is low and most commonly occurs in the early posttransplantation period. We report an unusual case of a 52-year-old female patient with Aspergillus endocarditis as a late complication after kidney transplantation, presumably spread from a necrosis in the gut, associated with previous cytomegalovirus colitis. As complications, the patient experienced septic embolization into the coronary and pulmonary arteries, and an infarction of the right parietal cortex and insula. The patient died as a result of global heart failure after a 10-day course of antimycotic therapy with amphotericin B plus 5-flucytosine during surgical valve replacement.

Clinicopathological features of cutaneous histoplasmosis in human immunodeficiency virus-infected patients in Zimbabwe.

Reports of disseminated Histoplasma infection in African AIDS patients are scanty. In Zimbabwe, 12 patients presented in 1994-2000 with facial nodular/papular cutaneous lesions, which became umbilicated and finally ulcerated. Histology revealed non-granulomatous inflammation and macrophages stuffed with Histoplasma. Recognition of these clinical features may lead to more rapid diagnosis of disseminated histoplasmosis in Africa.

Influence of antimicrobial treatment on mortality in septicemia.

OBJECTIVE: To determine the influence of antimicrobial therapy and of predisposing illness on the septicemia mortality rate. METHOD: All blood-culture-positive episodes of septicemia in the Department of Medicine at the University Hospital in Frankfurt between 1989 and 1993 were entered on a database. Underlying illnesses were classified as immunocompromising diseases (hematological malignancies, AIDS and others), severe chronic and chronic illnesses and no predisposing illnesses. Therapy was judged on the basis of the in-vitro-susceptibility of the organism ('appropriate') and the interval (no. of days) between the onset of septicemia and start of appropriate treatment noted. For mortality all deaths within 28 days after the onset of septicemia were counted. RESULTS: Overall mortality due to septicemia was 18.1%, ranging from 9.4% (organ transplantation) to 50% (liver cirrhosis) according to the underlying illness. Mortality in patients receiving appropriate treatment (83.1%) was 16% as opposed to 28%, if no appropriate treatment was given (p<0.001). Comparison of appropriate treatment started within and after 48 hours revealed a reduction in mortality from 30.9% to 15.4% for early appropriate therapy in patients with hematological malignancies (p<0.002). For septicemia in patients with AIDS and chronic illnesses mortality was significantly higher (p<0.05) if treatment remained inappropriate (AIDS 28.6%, chronic illness 33.3%), but was similar when early and delayed appropriate therapy were compared (AIDS: 13% vs. 12.8%, chronic illness 11.8% vs. 11.1%). CONCLUSION: First-line treatment regimens for septicemia in patients with hematological malignancies should include the greatest possible part of the spectrum of causative organisms. In contrast to that it may be acceptable to rely to some extent on a change of treatment, when treating septicemia in patients with chronic illnesses or AIDS. These considerations are of value in the debate on rising health care costs. Several other facts, such as the stable mortality rate of 8 - 12% in previously healthy patients and the range of mortality from 9.4 - 50%, if predisposing illnesses are present, indicate the existence of adverse factors influencing the outcome of septicemia in spite of appropriate therapy. These pathophysiological factors will have to be studied in detail in order to improve the prognosis of septicemia further.

Limited cleavage of tau with matrix-metalloproteinase MMP-9, but not MMP-3, enhances tau oligomer formation.

Tauopathies such as Alzheimer's disease or progressive supranuclear palsy are characterized by pathological deposits of aggregated protein tau. It has been shown that truncated tau is present in these deposits, and it was thus hypothesized that truncation of the protein may play a role in pathological aggregation processes. Furthermore, recent findings indicate that pro-aggregatory extracellular tau can be taken up by neurons and induce neurodegeneration. In this study, we investigated the effect of limited proteolysis by matrix-metalloproteinases 3 and 9 (MMP-3, MMP-9) as well as by the proteinases trypsine and Proteinase K (PK) on tau aggregation behavior. We applied single molecule fluorescence techniques to monitor early tau oligomer formation at nanomolar protein concentrations. We observed that tau is a substrate of both MMP-3 and MMP-9, and show that limited proteolysis by MMP-9, but not by MMP-3, PK or trypsine, increases tau oligomer formation. We further characterize tau fragments resulting from limited cleavage, demonstrating a distinct cleavage pattern for both MMP-3 and MMP-9. In summary, our data demonstrate that tau is a substrate of both MMP-3 and MMP-9, and show a differential influence of these enzymes on tau aggregation behavior, implicating a potential role in neurodegeneration.

Successful treatment of disseminated mucormycosis with a combination of liposomal amphotericin B and posaconazole in a patient with acute myeloid leukaemia.

The combination of resection of infected tissue and antifungal therapy is the treatment of choice in mucormycosis. In disseminated mucormycosis, where surgery is impossible, the mortality is almost 90%. We report the first case of disseminated mucormycosis that was cured with a combination therapy of liposomal amphotericin B and posaconazole without surgical intervention.

Diagnosis of invasive aspergillosis and mucormycosis in immunocompromised patients by seminested PCR assay of tissue samples.

Aspergillosis and mucormycosis are the most common mold infections in patients with hematological malignancies. Infections caused by species of the genus Aspergillus and the order Mucorales require different antifungal treatments depending on the in vitro susceptibility of the causative strain. Cultures from biopsy specimens frequently do not grow fungal pathogens, even from histopathologically proven cases of invasive fungal infection. Two seminested PCR assays were evaluated by amplifying DNA of zygomycetes and Aspergillus spp. from organ biopsies of 21 immunocompromised patients. The PCR assays correctly identified five cases of invasive aspergillosis and six cases of mucormycosis. They showed evidence of double mold infection in two cases. Both assays were negative in five negative controls and in two patients with yeast infections. Sequencing of the PCR products was in accordance with culture results in all culture-positive cases. In six patients without positive cultures but with positive histopathology, sequencing suggested a causative organism. Detection of fungal DNA from biopsy specimens allows rapid identification of the causative organism of invasive aspergillosis and mucormycosis. The use of these PCR assays may allow guided antifungal treatment in patients with invasive mold infections.

[Therapy of candidiasis and cryptococcosis in AIDS]. / Die Therapie der Candidose und Cryptococcose bei AIDS.

Fungal infections figures large in HIV-infected patients. Candida infections of the mucous membranes belong to the main manifestations of immunodeficiency in HIV infection. For therapy and prophylaxis of oropharyngeal candidosis mainly systemically acting azoles as ketoconazole, fluconazole and itraconazole are applied; antimycotics to be administered topically regularly fail to act in patients with progressing disease. Ketoconazole tablets were used with good success in previous years of the AIDS epidemics. Application of ketoconazole in liquid formulation led to a significant increase in efficacy. Subsequently fluconazole proved to be a triazole with evidently better pharmacological properties leading to good clinical efficacy. Presently it represents the drug of first choice in acute and maintenance therapy of recurrent oropharyngeal and oesopharyngeal candidosis. In the case of therapy failure with fluconazole the administration of itraconazole in liquid cyclodextrine formulation can replace or at least delay the administration of amphotericin B plus flucytosine, a therapy rich in toxic side effects. The standard therapy of disseminated cryptococcosis--particularly of cerebral manifestation--is still the administration of amphotericin B combined with flucytosine. Alternative drugs are represented by fluconazole and itraconazole. However, an azole monotherapy seems to be legitimate only in primary cryptococcosis of the lungs or in early stages of secondary extrapulmonary infection. Cryptococcal meningitis requires an intense initial therapy. New therapy strategies were developed combining azoles with standard antimycotic drugs. The value of amphotericin B in liposomal or lipid complex formulations is still undetermined due to the up to now low number of AIDS patients treated.(ABSTRACT TRUNCATED AT 250 WORDS)

[Therapy of systemic mycoses in immunodeficiency]. / Therapie von Systemmykosen bei Abwehrschwäche.

Fungal infections have gained importance recently. The major reason for this is the increasing number of patients with immunodeficiency. Systemic treatment of invasive fungal infections up to now has been based on relatively few antimycotic agents (amphotericin B, flucytosine, as well as the azole derivatives fluconazole and itraconazole). Only a few number of fungi cause the majority of opportunistic fungal infections. Candida albicans leads to severe mucosal infections in cases of immunodeficiency. Systemic mycoses usually present as endogenous infections or are caused by an infected central venous catheter with dissemination into multiple organs. Less severe candida infections should be treated with fluconazole. A more severe candida infection still requires treatment with amphotericin B plus flucytosine. Aspergillus fumigatus, a ubiquitous mold, is the most frequent pathogen in patients with granulocytopenia. First choice treatment also is amphotericin B and flucytosine; treatment should be started despite lacking proof of pathogen in patients with immunodeficiency and typical clinical signs. Itraconazole, the azole derivative active against aspergillus, may be administered only in mild cases of aspergillus infections in immunocompromised patients. Infections with Cryptococcus neoformans, which hardly ever occur, have been observed frequently in AIDS patients. The manifestation of cryptococcosis mainly presents as chronical meningitis. Presently various treatment concepts are being clinically tested. An initial combination of amphotericin B, flucytosine, and fluconazole, followed by long-term treatment with fluconazole, is recommended.

Prevalence of Aspergillus fumigatus and other fungal species in the sputum of adult patients with cystic fibrosis.

Aspergillus fumigatus is often found in the respiratory tract secretions of patients with cystic fibrosis (CF), although the role of the fungus for progression of pulmonary disease remains unclear. This study aimed to investigate the frequency of A. fumigatus and other fungi in sputum of adult CF patients using different methods for culture and microscopy. Results from the analysis of 369 samples from 94 patients showed that A. fumigatus could be isolated in 45.7% of patients. Other moulds were rare, but the yeast Candida albicans was another frequent isolate, detected in 75.5% of patients. A comparison of different culture media showed no difference between a selective medium developed to specifically inhibit Pseudomonas aeruginosa and a standard fungal culture medium for growth of A. fumigatus, although both were more efficient for detection of fungi than other bacterial culture media. Fluorescent microscopy with calcofluor white was more sensitive for detection of fungal hyphae in undiluted sputum than standard methylene blue staining. This study shows that A. fumigatus and C. albicans have a high frequency in adult CF patients. Microbiological analysis should routinely include methods for specific identification of fungi to monitor for potential complications arising from fungal disease in these patients.

Rapid PCR-based diagnosis of disseminated histoplasmosis in an AIDS patient.

Disseminated histoplasmosis is an unusual opportunistic infection in patients with advanced HIV infection living outside endemic areas. Diagnosis usually is made on the basis of isolation of Histoplasma capsulatum from clinical specimens or histologic examination. Reported is the case of an HIV-infected Columbian individual in whom the diagnosis of histoplasmosis was established within 24 h of collection of an adequate bronchoalveolar lavage specimen. The diagnosis was made by detection of specific fungal DNA and confirmed by isolation of Histoplasma capsulatum from blood, bone marrow and respiratory specimens 10 days later. The patient recovered under antifungal treatment and remained asymptomatic up to the last follow-up visit 6 months later. The polymerase chain reaction assay might be a powerful and rapid diagnostic tool for the diagnosis of non-European invasive fungal infections and should be further evaluated.

Diagnosis of disseminated zygomycosis using a polymerase chain reaction assay.

Invasive pulmonary zygomycosis is an uncommon opportunistic infection in patients with haematological malignancies. Clinical manifestations are in distinguishable from the more frequent invasive aspergillosis. Standard diagnostic methods like culture and microscopy from respiratory secretions have a low diagnostic sensitivity. A case in which proven invasive pulmonary zygomycosis was confirmed using a panfungal polymerase chain reaction assay in blood is presented. Since zygomycosis requires more aggressive treatment than aspergillosis (high-dose amphotericin B and surgical intervention), the polymerase chain reaction assay may improve the outcome of these often fatal infections by guiding the therapeutic approach through an early, non-invasive diagnosis.

Primary cytomegalovirus infection in an outpatient setting--laboratory markers and clinical aspects.

BACKGROUND: Occasionally, primary cytomegalovirus (CMV) infection may give rise to more or less severe clinical illness in immunocompetent adults. We retrospectively analyzed cases of acute CMV infection in medical outpatients. PATIENTS AND METHODS: Over a 6-year period, we identified 22 patients with a febrile illness and hepatitis suffering from primary CMV infection. This was diagnosed on the basis of a strongly positive CMV IgM antibody test result and/or CMV IgG seroconversion. Clinical features as well as relevant laboratory results were analyzed. We also tested available samples for CMV glycoprotein B-specific antibodies and CMV IgG avidity and analyzed results of Epstein-Barr virus (EBV)-specific antibody assays. In addition, current age-specific CMV IgG seroprevalence rates were determined using 9,870 routine patient samples. RESULTS: At presentation, all patients complained of malaise and fever higher than 38 degrees C, and many also complained of cephalgia. Most patients who underwent abdominal ultrasonography had an enlargement of the spleen. Most patients had a relative lymphocytosis but only three had a mild leukocytosis. C-reactive protein was only slightly elevated in 13 patients; all 22 patients had elevated levels of alanine aminotransferase (ALT) and lactate dehydrogenase (LDH). Half the patients reported travel to areas outside western Europe, mostly to tropical and subtropical areas, within 3 weeks before onset of illness. Primary CMV infection was confirmed by negative anti-gB antibody test results and the absence of high-avidity CMV antibodies. In contrast, despite past EBV infection demonstrated by positive anti-EBNA-1 results, 15 out of 21 patients tested for EBV markers had positive or nonspecific IgM test results. The overall CMV IgG seroprevalence rate in the routine samples was 64.4%, with marked age-dependent increases. CONCLUSION: CMV is a relevant differential diagnosis in feverish illnesses accompanied by hepatitis in otherwise healthy adults, about 40% of whom are CMV-naïve. Half our patients seem to have acquired their CMV infection abroad, so that a diagnosis of CMV infection needs to be taken into account in travelers, in addition to infectious illnesses more commonly considered in this context, such as dengue or hepatitis A. For diagnosis, both CMV and EBV antibody studies should be performed and the inclusion of assays able to demonstrate past infection is helpful for achieving a definite diagnosis.

Travel-acquired dengue infection: clinical spectrum and diagnostic aspects.

BACKGROUND: Dengue fever is increasingly recognized in travelers returning from endemic areas with acute febrile illness; however, its true burden in nonendemic countries is unknown. Only few studies focus on clinical manifestations and serological findings in primarily nonimmune individuals. PATIENTS AND METHODS: We analyzed the epidemiology, clinical manifestations and virological results in patients with imported acute dengue infection who presented at our travel clinic in Frankfurt am Main, Germany, between September 1998 and November 2000. An immunochromatographic test and an immunofluorescence assay were used for antibody testing. RESULTS: Dengue fever was confirmed in 13 patients, thus being the second commonest tropical infection after malaria in patients with fever and a travel history to a tropical country (18 cases per 1,000 patient visits per year). Most patients had only spent a short time abroad, either in South Central or South East Asia or in the Caribbean. CONCLUSION: The clinical features considered typical for dengue were not always present. Antibody assays were typically negative early in the course of disease, with seroconversion occurring only after cessation of clinical symptoms. A high index of suspicion is needed in these patients who often present without typical features of dengue and whose early antibody tests may be negative.

Case report. Successful therapy of disseminated histoplasmosis in AIDS with liposomal amphotericin B.

A 36-year-old HIV-infected male patient presented with relapsing fever episodes to 39 degrees C, night sweats and weight loss. Computerized tomography of the abdomen showed enlarged multiple lymph nodes. After surgical resection of multiple lymph nodes, disseminated infection with Histoplasma capsulatum was diagnosed. Amphotericin B desoxycholate was initiated for 24 days. Fourteen days after therapy was discontinued, the patient suffered similar symptoms again. Subsequent treatment with liposomal amphotericin B led to rapid improvement within 3 days. Upon discharge, maintenance therapy with 600-mg itraconazole capsules was initiated and decreased to 400-mg 14-days later. Itraconazole therapy was continued until the patient died more than 2 years later because of complications of the underlying disease. At autopsy there were no signs of histoplasmosis.