The impact of ABCC11 polymorphisms on the risk of early-onset fluoropyrimidine toxicity

A missense variant (c.1637C>T, T546M) in ABCC11 encoding the MRP8 (multidrug resistance protein 8), a transporter of 5-fluorodeoxyuridine monophosphate, has been associated with an increased risk of 5-fluorouracil-related severe leukopenia. To validate this association, we investigated the impact of the ABCC11 variants c.1637C>T, c.538G>A and c.395+1087C>T on the risk of early-onset fluoropyrimidine-related toxicity in 514 cancer patients. The ABCC11 variant c.1637C>T was strongly associated with severe leukopenia in patients carrying risk variants in DPYD, encoding the key fluoropyrimidine-metabolizing enzyme dihydropyrimidine dehydrogenase (odds ratio (OR): 71.0; 95% confidence interval (CI): 2.5-2004.8; Pc.1637C>T*DPYD=0.013). In contrast, in patients without DPYD risk variants, no association with leukopenia (OR: 0.95; 95% CI: 0.34-2.6) or overall fluoropyrimidine-related toxicity (OR: 1.02; 95% CI: 0.5-2.1) was observed. Our study thus suggests that c.1637C>T affects fluoropyrimidine toxicity to leukocytes particularly in patients with high drug exposure, for example, because of reduced fluoropyrimidine catabolism.

The recent eutrophication of Baldeggersee (Switzerland) as assessed by fossil diatom assemblages

Diatom analyses with an annual resolution were carried out on varves of the hypertrophic Baldeggersee (Central Swiss Plateau) for the timespan ad 1885 to 1993. They reveal seven major changes in the dominant planktonic diatoms. As a result of progressive nutrient enrichment, Baldeggersee changed in the 1910s from a Cyclotella to a Tabellaria fenestrata dominated assemblage, and eventually in the 1950s to a Stephanodiscus parvus dominated diatom assemblage. The timing and direction of diatom-assemblage changes in the varved sediment compare well with sedimentological and limnological observations. Partitioning of the variance in the diatom data revealed that TP is a stronger explanatory variable than temperature for these changes. A diatom-inferred total phosphorus (TP) reconstruction indicates three major steps in eutrophication, occurring at 1909, the mid-1950s and the mid-1970s. Comparison with TP measurements in the water column demonstrates that the diatom-TP inference model used is able to hindcast past TP concentrations reliably. The major steps in eutrophication led to decreases in diatom diversity and also resulted in a progressive increase of calcite grain-size. The lake restoration programme established since 1982 shows no direct impact on the composition of the diatom assemblages. However, the decrease in phosphorus loads since the mid-1970s is reflected in the diatom assemblages and in decreasing diatom-inferred TP concentrations.

Record linkage to correct under-ascertainment of cancers in HIV cohorts: the Sinikithemba HIV clinic linkage project.

The surveillance of HIV-related cancers in South Africa is hampered by the lack of systematic collection of cancer diagnoses in HIV cohorts and the absence of HIV status in cancer registries. To improve cancer ascertainment and estimate cancer incidence, we linked records of adults (aged ≥ 16 years) on antiretroviral treatment (ART) enrolled at Sinikithemba HIV clinic, McCord Hospital in KwaZulu-Natal (KZN) with the cancer records of public laboratories in KZN province using probabilistic record linkage methods. We calculated incidence rates for all cancers, Kaposi sarcoma (KS), cervix, non-Hodgkin's lymphoma and non-AIDS defining cancers (NADCs) before and after inclusion of linkage-identified cancers with 95% confidence intervals (CI). A total of 8,721 records of HIV-positive patients were linked with 35,536 cancer records. Between 2004 and 2010 we identified 448 cancers, 82% (n=367) were recorded in the cancer registry only, 10% (n=43) in the HIV cohort only and 8% (n=38) both in the HIV cohort and the cancer registry. The overall cancer incidence rate in patients starting ART increased from 134 (95% CI 91-212) to 877 (95% CI 744-1,041) after inclusion of linkage-identified cancers. Incidence rates were highest for KS (432, 95% CI 341-555), followed by cervix (259, 95% CI 179-390) and NADCs (294, 95% CI 223-395) per 100,000 person-years. Ascertainment of cancer in HIV cohorts is incomplete, probabilistic record linkage is both feasible and essential for cancer ascertainment. This article is protected by copyright. All rights reserved.

Ms.Ff.F.Stoltze 3. 206 - Brief von Karl Gustav Odermann an Friedrich Stoltze

Stoltze: Gedicht in den Berichten des Freien Deutschen Hochstifts (1880, S. 395), Bitte um Abschrift des Stoltze-Gedichts zu Friedrich Schillers 100. Geburtstag

Bericht über die klimatischen und sanitären Verhältnisse des Kamerun- und Sanagaflußgebietes (Duala-Edea) in der Zeit vom 1. Juli 1900 bis 30. Juni 1901

A. Plehn

Na 1 Nachlass Max Horkheimer, 640 - "Simmel and Freudian Philosophy", "Authoritarianism and the Family Today" und "The Chances of Democracy in Germany" (p. IX 18.1-3-IX 19a)

"Simmel and Freudian Philosophy" (GS 5, S. 396-405); 1. Nachruf, verlesen beim Memorial Meeting for Ernst Simmel; datiert: 13.12.1947; veröffentlicht in: International Journal of Psychoanalysis, 29. Jahrgang, 1948, S. 110-113; 2. Abschrift aus Werken und Briefen Siegmund Freuds; Typoskript, 9 Blatt; 3. Freeman, Burriel: 1 Brief mit Unterschirft an Max Horkheimer, Chicago, 10.06.1949; 1 Brief von Max Horkheimer, Los Angeles, 15.06.1949, 2 Blatt; "Authoritarianism and the Family Today" (GS 5, S. 377-395); 1. Aufsatz, datiert 1947, veröffentlicht in: Ruth Nanda Anshen (editor), "The Family: Its Function and Distiny", New York 1949. a) Typsokript, 20 Blatt b) Typoskript mit handschriftlichen Korrekturen, 20 Blatt c) Typoskript mit eigenhändigen Korrekturen, 20 Blatt d)-f) deutsche Fassung mit dem Titel "Autorität und Familie", übersetzt vom Institut für Sozialforschung, 1960; veröffentlicht in : "Erkenntnis und Verantwortung. Festschrift für Theodor Litt", Düsseldorft, 1960 d) Typoskript, 20 Blatt e) Typoskript, 20 Blatt f) Korrekturfahnen aus der Litt- Festschrift, mit dem Titel "Autorität und Familie in der Gegenwart"; 6 Blatt; 2. Schönbach, Peter: 1 Brief mit Unterschrift an Max Horkheier, ohne Ort, 23.06.1960; 1 Blatt; 3. Schönbach, Peter: 1 Brief mit Unterschrift an Friedrich Pollock, ohne Ort, 22.06.1960; 1 Blatt; "The Chances of Democracy in Germany" (GS 12, S. 184-194); 1947 [?] a) Typoskript, 10 Blatt b) Typoskript mit eigenhändigen Korrekturen, 11 Blatt c) Typoskript mit eigenhändigen Korrekturen ,11 Blatt;

Lehrbuch der Hebammenkunst

von Johann Christian Gottfried Jörg

Morijah. Religiöse Lehrvorträge (Schiurim) für die Sabbathe und Festtage des Jahres : zur Erbauung, Belehrung und Fortbildung

von J. Goldschmidt

EPIDEMIOLOGIC TRENDS OF LUNG DISEASE DUE TO MYCOBACTERIA KANSASII AND AVIUM-INTRACELLULARE IN TEXAS, 1977-1983

This study compared the reported isolations of Mycobacterium kansasii (MK) and Myobacterium avium-intracellulare (MAI) with Mycobacterium tuberculosis (MTB) between 1977-1983 in Texas. A total of 15,395 mycobacterial cases were identified of which 1,352 (8.8%) were MK or MAI. The incidence of MK was higher in urban areas than nonurban areas (p < .005). The incidence of MAI has increased in the Dallas metroplex from 34 cases to 251 for the same time period. Although the number of MK cases previously reported has always exceeded those of MAI, the numbers were equal in the last year (1983) of the study.^ More than 75% of patients with MK or MAI were Caucasians compared to only 18% of patients with MTB. Male to female ratios for MK and MAI are 3:1 and 3:2, respectively. The age distribution of MK patients were an average of 5 years younger than patients with MAI, a finding which concurs with previous studies. MK and MAI pulmonary infections continue to be absent among children and relatively absent among Hispanics.^ MK appears to be associated with occupations in construction, whereas MAI is more often associated with farm work. ^

Exposure to nonsteroidal anti-inflammatory drugs and weight loss and hospitalization in non-small cell lung cancer patients

Background. Cancer cachexia is a common syndrome complex in cancer, occurring in nearly 80% of patients with advanced cancer and responsible for at least 20% of all cancer deaths. Cachexia is due to increased resting energy expenditure, increased production of inflammatory mediators, and changes in lipid and protein metabolism. Non-steroidal anti-inflammatory drugs (NSAIDs), by virtue of their anti-inflammatory properties, are possibly protective against cancer-related cachexia. Since cachexia is also associated with increased hospitalizations, this outcome may also show improvement with NSAID exposure. ^ Design. In this retrospective study, computerized records from 700 non-small cell lung cancer patients (NSCLC) were reviewed, and 487 (69.57%) were included in the final analyses. Exclusion criteria were severe chronic obstructive pulmonary disease, significant peripheral edema, class III or IV congestive heart failure, liver failure, other reasons for weight loss, or use of research or anabolic medications. Information on medication history, body weight and hospitalizations was collected from one year pre-diagnosis until three years post-diagnosis. Exposure to NSAIDs was defined if a patient had a history of being treated with NSAIDs for at least 50% of any given year in the observation period. We used t-test and chi-square tests for statistical analyses. ^ Results. Neither the proportion of patients with cachexia (p=0.27) nor the number of hospitalizations (p=0.74) differed among those with a history of NSAID use (n=92) and those without (n=395). ^ Conclusions. In this study, NSAID exposure was not significantly associated with weight loss or hospital admissions in patients with NSCLC. Further studies may be needed to confirm these observations.^

Population-based cross -sectional survey on intestinal helminth infections with a focus on taeniasis among residents of El Paso, Texas and Ciudad Juarez, Mexico

Few studies have been conducted on the epidemiology of enteric infectious diseases of public health importance in communities along the United States-Mexico border, and these studies typically focus on bacterial and viral diseases. The epidemiology of intestinal helminth infections along the border has not recently been explored, and there are no published reports for El Paso and Ciudad Juarez, both of which are high traffic urban areas along the Texas-Mexico border. The purpose of this research project was to conduct a cross-sectional epidemiologic survey for enteric helminths of medical importance along the Texas-Mexico border region of El Paso and Ciudad Juarez and to evaluate risk factors for exposure to these parasites. In addition, an emphasis was placed on the zoonotic tapeworm, Taenia solium. This tapeworm is especially important in this region because of the increasing incidence of neurocysticercosis, a severe disease spread by carriers of intestinal T. solium. Fecal samples were collected from individuals of all ages in a population-based cross-sectional household survey and evaluated for the presence of helminth parasites using fecal flotations. In addition, a Taenia coproantigen enzyme linked immunosorbent assay (ELISA) was performed on each stool sample to identify tapeworm carriers. A standardized questionnaire was administered to identify risk factors and routes of exposure for enteric helminth infections with additional questions to assess risk factors specific for taeniasis. The actual prevalence of taeniasis along the Texas-Mexico border was unknown, and this is the first population-based study performed in this region. Flotations were performed on 395 samples and four (1%) were positive for helminths including Ascaris, hookworms and Taenia species. Immunodiagnostic testing demonstrated a prevalence of 2.9% (11/378) for taeniasis. Based on the case definition, a 3% (12/395) prevalence of taeniasis was detected in this area. In addition, statistical analyses indicate that residents of El Paso are 8.5 times more likely to be a tapeworm carrier compared to residents of Juarez (PR=8.5, 95% CI=2.35, 30.81). This finding has important implications in terms of planning effective health education campaigns to decrease the prevalence of enteric helminths in populations along the Texas-Mexico border. ^