[Molecular analyses for (early) recognition of hematologic diseases - sense and sensibility for molecular analysis: the art of intelligent decision-making]

During the last 10 years several molecular markers have been established as useful tools among the armamentarium of a hematologist. As a consequence, the number of performed hematologic molecular analyses has immensely increased. Often, such tests replace or complement other laboratory methods. Molecular markers can be useful in many ways: they can serve for diagnostics, describe the prognostic profile, predict which types of drugs are indicated, and can be used for the therapeutic monitoring of the patient to indicate an adequate response or predict resistance or relapse of the disease. Many markers fulfill more than one of these aspects. Most important, however, is the right choice of analyses at the right time-points!

Oral mucosal lesions diagnosed in a stomatology service. An examination of clinico-pathological findings from the year 2003

During 2003, a total of 258 new patients with oral soft tissue lesions were admitted at the Stomatology Service of the Department of Oral Surgery and Stomatology at the University of Berne. For the present study, 185 patients with clinically and histopathologically verified diagnoses were included. The following data was collected: prevalence of oral mucosal lesions, distribution of benign, precancerous and malign lesions in different age groups, and the concordance of the referral with the working diagnosis at the Stomatology Service. The most frequent pathological soft tissue findings were fibrous hyperplasias (n = 44) and oral lichen planus (n = 30). Precancerous lesions were present in 41 cases (30 patients with oral lichen planus, eleven oral leukoplakias), and ten patients had oral malignomas. Most lesions were found in patients between the age of 40 and 60 years. The referral diagnosis concurred in 36.6% (n = 67) of the cases with the definite diagnosis before initiation of treatment, the working diagnosis in 70% (n = 128) of the cases. Therefore, it can be concluded that a specialised Stomatology Service serves as a center of competence due to large numbers of patients/cases seen and treated, and the resulting high level of clinical experience of the staff. Moreover, it is important in the primary diagnosis of oral squamous cell carcinoma, in collaboration with the referring dentist in private practice.

Early loss of HIV-infected patients on potent antiretroviral therapy programmes in lower-income countries

OBJECTIVE: To analyse the early loss of patients to antiretroviral therapy (ART) programmes in resource-limited settings. METHODS: Using data on 5491 adult patients starting ART (median age 35 years, 46% female) in 15 treatment programmes in Africa, Asia and South America with (3) 12 months of follow-up, we investigated risk factors for no follow-up after treatment initiation, and loss to follow-up or death in the first 6 months. FINDINGS: Overall, 211 patients (3.8%) had no follow-up, 880 (16.0%) were lost to follow-up and 141 (2.6%) were known to have died in the first 6 months. The probability of no follow-up was higher in 2003-2004 than in 2000 or earlier (odds ratio, OR: 5.06; 95% confidence interval, CI: 1.28-20.0), as was loss to follow-up (hazard ratio, HR: 7.62; 95% CI: 4.55-12.8) but not recorded death (HR: 1.02; 95% CI: 0.44-2.36). Compared with a baseline CD4-cell count (3) 50 cells/microl, a count < 25 cells/microl was associated with a higher probability of no follow-up (OR: 2.49; 95% CI: 1.43-4.33), loss to follow-up (HR: 1.48; 95% CI: 1.23-1.77) and death (HR: 3.34; 95% CI: 2.10-5.30). Compared to free treatment, fee-for-service programmes were associated with a higher probability of no follow-up (OR: 3.71; 95% CI: 0.97-16.05) and higher mortality (HR: 4.64; 95% CI: 1.11-19.41). CONCLUSION: Early patient losses were increasingly common when programmes were scaled up and were associated with a fee for service and advanced immunodeficiency at baseline. Measures to maximize ART programme retention are required in resource-poor countries.

History of Art in the Digital Age: Problems and Possibilities

Ziel der vorliegenden Arbeit ist, einen allgemeinen Überblick über die Wirkung von Computern auf die Kunstgeschichte zu geben. Zu Beginn der Arbeit wird der Charakter der informationstechnologischen Revolution untersucht, einschließlich seiner schon oft festgestellten Parallelen mit der "Gutenberg"- Revolution, deren Ausgangspunkt in der Entwicklung der Druckerpresse liegt. Wie auch bei Gutenberg, ist die Entwicklung der Informationstechnologie technologisch bedingt. Jedoch führt sie durch ihren Schwerpunkt auf Flexibilität und Verbreitung an ein anderes Ziel. Diese Flexibilität ist zweischneidig: während sie viele neue Möglichkeiten eröffnet, scheint sie auch einen bruchstückhafteren, iterativen Ansatz zur Untersuchung des Vorzugs von Information vor Wissen anzuregen. Es bleibt jedoch offen, ob dieser Ansatz als notwendige Konsequenz der Struktur dieser vorhandenen neuen Technologie betrachtet werden kann, oder ob er eher als Produkt eines allgemeinen intellektuellen Wandels, angeregt durch das Aufkommen des postmodernen Diskurses, beschrieben werden soll. Ich werde in dem vorliegenden Artikel für den zweitgenannten Grund argumentieren. Ich bin außerdem der Meinung, dass der in der neuen Technologie enthaltenen Tendenz zur Fragmentierung entgegengewirkt werden kann - vorausgesetzt der Wunsch besteht. Die Entwicklung des Computers hängt eng mit der Nachfrage des Konsumenten zusammen. Aus diesem Grund kann ein neuer Trend in der Nachfrage die Art der Ausweitung und Modifizierung technologischer Vorgänge mitbestimmen.Des weiteren werden in der vorliegenden Arbeit Problemstellungen diskutiert, die speziell Auswirkungen auf die Untersuchung von Bildern haben. Hierbei wird sowohl das Potential digitaler Bilder für neue Formen der Erforschung und Analyse diskutiert, als auch die vielen neuen Möglichkeiten im Zeitalter des Internets.

E-learning - an approach to teaching art history in the Internet age

Der erste Universitätskurs in Norwegen, der komplett via Internet unterrichtet wird, wird in Kunstgeschichte angeboten. Dieses Projekt wurde im März 2000 mit einem Einführungskurs in die Kunstgeschichte gestartet. Aufgrund seiner modularen Struktur, visuell ansprechender Präsentationen, fachbezogener Ansätze sowie Möglichkeiten eines zweiseitigen Kommunikationsaustausches, kann das Interesse und der Einbezug der Studenten während der zweijährigen Dauer des Kurses aufrecht erhalten werden.

Immune recovery after starting ART in HIV-infected patients presenting and not presenting with tuberculosis in South Africa

We studied the immune response after starting antiretroviral treatment (ART) in 15,646 HIV-infected patients with or without tuberculosis (TB) at presentation in 3 ART programs in South Africa between 2003 and 2010. Patients presenting with TB had similar increases in CD4 cells compared with all other patients (adjusted difference 4.9 cells/µL per 6 months, 95% confidence interval: 0.2 to 9.7). Younger age, advanced clinical stage, female sex, and lower CD4 cell count at ART start were all associated with steeper CD4 slopes. In South Africa, HIV-infected patients presenting with TB experience immune recovery after starting ART that is no worse than in other patients.

Adherence as a Predictor of the Development of Class-Specific Resistance Mutations: The Swiss HIV Cohort Study

Background Non-adherence is one of the strongest predictors of therapeutic failure in HIV-positive patients. Virologic failure with subsequent emergence of resistance reduces future treatment options and long-term clinical success. Methods Prospective observational cohort study including patients starting new class of antiretroviral therapy (ART) between 2003 and 2010. Participants were naïve to ART class and completed ≥1 adherence questionnaire prior to resistance testing. Outcomes were development of any IAS-USA, class-specific, or M184V mutations. Associations between adherence and resistance were estimated using logistic regression models stratified by ART class. Results Of 314 included individuals, 162 started NNRTI and 152 a PI/r regimen. Adherence was similar between groups with 85% reporting adherence ≥95%. Number of new mutations increased with increasing non-adherence. In NNRTI group, multivariable models indicated a significant linear association in odds of developing IAS-USA (odds ratio (OR) 1.66, 95% confidence interval (CI): 1.04-2.67) or class-specific (OR 1.65, 95% CI: 1.00-2.70) mutations. Levels of drug resistance were considerably lower in PI/r group and adherence was only significantly associated with M184V mutations (OR 8.38, 95% CI: 1.26-55.70). Adherence was significantly associated with HIV RNA in PI/r but not NNRTI regimens. Conclusion Therapies containing PI/r appear more forgiving to incomplete adherence compared with NNRTI regimens, which allow higher levels of resistance, even with adherence above 95%. However, in failing PI/r regimens good adherence may prevent accumulation of further resistance mutations and therefore help to preserve future drug options. In contrast, adherence levels have little impact on NNRTI treatments once the first mutations have emerged.

Gene Therapy for Pediatric Cancer: State of the Art and Future Perspectives.

While modern treatments have led to a dramatic improvement in survival for pediatric malignancy, toxicities are high and a significant proportion of patients remain resistant. Gene transfer offers the prospect of highly specific therapies for childhood cancer. "Corrective" genes may be transferred to overcome the genetic abnormalities present in the precancerous cell. Alternatively, genes can be introduced to render the malignant cell sensitive to therapeutic drugs. The tumor can also be attacked by decreasing its blood supply with genes that inhibit vascular growth. Another possible approach is to modify normal tissues with genes that make them more resistant to conventional drugs and/or radiation, thereby increasing the therapeutic index. Finally, it may be possible to attack the tumor indirectly by using genes that modify the behavior of the immune system, either by making the tumor more immunogenic, or by rendering host effector cells more efficient. Several gene therapy applications have already been reported for pediatric cancer patients in preliminary Phase 1 studies. Although no major clinical success has yet been achieved, improvements in gene delivery technologies and a better understanding of mechanisms of tumor progression and immune escape have opened new perspectives for the cure of pediatric cancer by combining gene therapy with standard therapeutic available treatments.

A different perspective on poverty in Lao PDR: Multidimensional poverty in Lao PDR for the years 2002/2003 and 2007/2008

This paper presents an indicator for measuring multidimensional poverty in the Lao People’s Democratic Republic applying the Alkire–Foster methodology to the Lao Expenditure and Consumption Survey 2002/2003 and 2007/2008. We calculated a multidimensional poverty index (MPI) that includes three dimensions: education, health, and standard of living. Making use of the MPI’s decomposability, we analyse how much each of the different dimensions and its respective indicators contribute to the overall MPI. We find a marked reduction in the multidimensional poverty headcount ratio over the study period, regardless of how the indicators are weighted or how the deprivation and poverty cut-offs are set. This reduction is based on improvements regarding all indicators except cooking fuel and nutrition. We observe no significant reduction in the intensity of poverty, however; there are wide disparities between the country’s regions and between urban and rural areas. The proportion of poor people in rural areas is more than twice as high as that in urban areas. By complementing the traditional income-based poverty measure, we hope to provide useful information that can support knowledge-based decision-making for poverty alleviation.

Self-reported nonadherence to antiretroviral therapy as a predictor of viral failure and mortality.

OBJECTIVE To determine the effect of nonadherence to antiretroviral therapy (ART) on virologic failure and mortality in naive individuals starting ART. DESIGN Prospective observational cohort study. METHODS Eligible individuals enrolled in the Swiss HIV Cohort Study, started ART between 2003 and 2012, and provided adherence data on at least one biannual clinical visit. Adherence was defined as missed doses (none, one, two, or more than two) and percentage adherence (>95, 90-95, and <90) in the previous 4 weeks. Inverse probability weighting of marginal structural models was used to estimate the effect of nonadherence on viral failure (HIV-1 viral load >500 copies/ml) and mortality. RESULTS Of 3150 individuals followed for a median 4.7 years, 480 (15.2%) experienced viral failure and 104 (3.3%) died, 1155 (36.6%) reported missing one dose, 414 (13.1%) two doses and, 333 (10.6%) more than two doses of ART. The risk of viral failure increased with each missed dose (one dose: hazard ratio [HR] 1.15, 95% confidence interval 0.79-1.67; two doses: 2.15, 1.31-3.53; more than two doses: 5.21, 2.96-9.18). The risk of death increased with more than two missed doses (HR 4.87, 2.21-10.73). Missing one to two doses of ART increased the risk of viral failure in those starting once-daily (HR 1.67, 1.11-2.50) compared with those starting twice-daily regimens (HR 0.99, 0.64-1.54, interaction P = 0.09). Consistent results were found for percentage adherence. CONCLUSION Self-report of two or more missed doses of ART is associated with an increased risk of both viral failure and death. A simple adherence question helps identify patients at risk for negative clinical outcomes and offers opportunities for intervention.

Kurt Art, Brustbild

Signatur des Originals: S 36/F02610

Goethe im 67. Jahre, Zur Erinnerung an Goethe's 150 jähr. Geburtstag 28. Aug. 1899 : Goethe's Wohnhaus am Frauenplan zu Weimar, Blick vom Garten auf das Arbeits- u. Sterbezimmer

Signatur des Originals: S 36/F04206