Behavior maintained by intravenous injection of codeine, cocaine, and etorphine in the rhesus macaque and the pigtail macaque

Lever-pressing behavior of two species of macaque, the rhesus macaque ( M. mulatta ) and the pigtail macaque ( M. nemestrina ) was maintained by intravenous injection of codeine, etorphine, or cocaine. Monkeys responded under a fixed-ratio 30 timeout 600 s schedule of drug injection during two daily experimental sessions. Drug-maintained behavior was studied under two access conditions. Under the first condition, selected doses of codeine or cocaine were available for ten consecutive sessions. Under the second condition, responding was maintained by 0.32 mg/kg codeine or 0.32 mg/kg cocaine, and saline and selected doses of codeine, etorphine, and cocaine were substituted during single experimental sessions. Performance varied with drug and injection dose, access condition, and macaque species. For all three drugs, response rate increased and then decreased as injection dose increased. Maximal rates were maintained by 0.10–0.32 mg/kg codeine, 0.0003–0.001 mg/kg etorphine, and 0.10–0.32 mg/kg cocaine. A cocaine dose of 0.32 mg/kg maintained higher rates than any dose of codeine or etorphine, and maintained higher rates when available during consecutive sessions than when substituted for codeine for a single session. Codeine maintained similar rates under all access conditions. The pigtail macaques had short catheter lives, did not readily acquire codeine-maintained responding, and displayed lower rates of drug-maintained lever pressing than the rhesus macaques.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/46415/1/213_2004_Article_BF00427883.pd

Clonal karyotype evolution involving ring chromosome 1 with myelodysplastic syndrome subtype RAEB-t progressing into acute leukemia

s Karyotypic evolution is a well-known phenomenon in patients with malignant hernatological disorders during disease progression. We describe a 50-year-old male patient who had originally presented with pancytopenia in October 1992. The diagnosis of a myelodysplastic syndrome (MDS) FAB subtype RAEB-t was established in April 1993 by histological bone marrow (BM) examination, and therapy with low-dose cytosine arabinoside was initiated. In a phase of partial hernatological remission, cytogenetic assessment in August 1993 revealed a ring chromosome 1 in 13 of 21 metaphases beside BM cells with normal karyotypes {[}46,XY,r(1)(p35q31)/46,XY]. One month later, the patient progressed to an acute myeloid leukemia (AML), subtype M4 with 40% BM blasts and cytogenetic examination showed clonal evolution by the appearance of additional numerical aberrations in addition to the ring chromosome{[}46,XY,r(1),+8,-21/45,XY,r(1),+8,-21,-22/46, XY]. Intensive chemotherapy and radiotherapy was applied to induce remission in preparation for allogeneic bone marrow transplantation (BMT) from the patient's HLA-compatible son. After BMT, complete remission was clinically, hematologically and cytogenetically (normal male karyotype) confirmed. A complete hematopoietic chimerism was demonstrated. A relapse in January 1997 was successfully treated using donor lymphocyte infusion and donor peripheral blood stem cells (PB-SC) in combination with GM-CSF as immunostimulating agent in April 1997, and the patient's clinical condition remained stable as of January 2005. This is an interesting case of a patient with AML secondary to MDS. With the ring chromosome 1 we also describe a rare cytogenetic abnormality that predicted the poor prognosis of the patient, but the patient could be cured by adoptive immunotherapy and the application of donor's PB-SC. This case confirms the value of cytogenetic analysis in characterizing the malignant clone in hernatological neoplasias, the importance of controlling the quality of an induced remission and of the detection of a progress of the disease. Copyright (c) 2006 S. Karger AG, Basel

Hormone replacement therapy, body mass, and the risk of colorectal cancer among postmenopausal women from Germany

Previous studies have reported inconsistent results regarding the modifying effect of hormone replacement therapy (HRT) on the association of body mass index (BMI) and the risk of colorectal cancer (CRC) among postmenopausal women. We assessed the use of HRT and BMI in 208 postmenopausal women with histologically confirmed incident CRC and 246 controls in a population-based case–control study in Germany (DACHS study). Ever use of HRT was strongly associated with reduction of CRC risk (adjusted odds ratio 0.41, 95% confidence interval 0.25–0.67). Among nonusers of HRT, risk of CRC was strongly increased in women with BMI 27 to <30 kg m−2 (2.76, 1.07–7.12) and obese women (3.30, 1.25–8.72), when compared with women with BMI <23 kg m−2 (P for trend <0.01). BMI was not associated with risk of CRC among HRT users (P for interaction <0.01). In contrast to most other studies, a positive association of BMI and CRC risk was found among nonusers of HRT, but not among users of HRT. The reasons for the inconsistency of results regarding the potential risk modifying effect of postmenopausal hormones in the association of BMI with CRC remain inconclusive and require further study

Gender differences in colorectal cancer: implications for age at initiation of screening

There is some variation regarding age at initiation of screening for colorectal cancer (CRC) between countries, but the same age of initiation is generally recommended for women and men within countries, despite important gender differences in the epidemiology of CRC. We have explored whether, and to what extent, these differences would be relevant regarding age at initiation of CRC screening. Using population-based cancer registry data from the US and national mortality statistics from different countries, we looked at cumulative 10-year incidence and mortality of CRC reached among men at ages 50, 55, and 60, and found that women mainly reached equivalent levels when 4 to 8 years older. The gender differences were remarkably constant across populations and over time. These patterns suggest that gender differentiation of age at initiation may be worthwhile to utilise CRC-screening resources more efficiently

Geographical variations in the benefit of applying a prioritization system for cataract surgery in different regions of Spain

<p>Abstract</p> <p>Background</p> <p>In Spain, there are substantial variations in the utilization of health resources among regions. Because the need for surgery differs in patients with appropriate surgical indication, introducing a prioritization system might be beneficial. Our objective was to assess geographical variations in the impact of applying a prioritization system in patients on the waiting list for cataract surgery in different regions of Spain by using a discrete-event simulation model.</p> <p>Methods</p> <p>A discrete-event simulation model to evaluate demand and waiting time for cataract surgery was constructed. The model was reproduced and validated in five regions of Spain and was fed administrative data (population census, surgery rates, waiting list information) and data from research studies (incidence of cataract). The benefit of introducing a prioritization system was contrasted with the usual first-in, first-out (FIFO) discipline. The prioritization system included clinical, functional and social criteria. Priority scores ranged between 0 and 100, with greater values indicating higher priority. The measure of results was the waiting time weighted by the priority score of each patient who had passed through the waiting list. Benefit was calculated as the difference in time weighted by priority score between operating according to waiting time or to priority.</p> <p>Results</p> <p>The mean waiting time for patients undergoing surgery according to the FIFO discipline varied from 1.97 months (95% CI 1.85; 2.09) in the Basque Country to 10.02 months (95% CI 9.91; 10.12) in the Canary Islands. When the prioritization system was applied, the mean waiting time was reduced to a minimum of 0.73 months weighted by priority score (95% CI 0.68; 0.78) in the Basque Country and a maximum of 5.63 months (95% CI 5.57; 5.69) in the Canary Islands. The waiting time weighted by priority score saved by the prioritization system varied from 1.12 months (95% CI 1.07; 1.16) in Andalusia to 2.73 months (95% CI 2.67; 2.80) in Aragon.</p> <p>Conclusion</p> <p>The prioritization system reduced the impact of the variations found among the regions studied, thus improving equity. Prioritization allocates the available resources within each region more efficiently and reduces the waiting time of patients with greater need. Prioritization was more beneficial than allocating surgery by waiting time alone.</p

De novo Assembly of a 40 Mb Eukaryotic Genome from Short Sequence Reads: Sordaria macrospora, a Model Organism for Fungal Morphogenesis

Filamentous fungi are of great importance in ecology, agriculture, medicine, and biotechnology. Thus, it is not surprising that genomes for more than 100 filamentous fungi have been sequenced, most of them by Sanger sequencing. While next-generation sequencing techniques have revolutionized genome resequencing, e.g. for strain comparisons, genetic mapping, or transcriptome and ChIP analyses, de novo assembly of eukaryotic genomes still presents significant hurdles, because of their large size and stretches of repetitive sequences. Filamentous fungi contain few repetitive regions in their 30–90 Mb genomes and thus are suitable candidates to test de novo genome assembly from short sequence reads. Here, we present a high-quality draft sequence of the Sordaria macrospora genome that was obtained by a combination of Illumina/Solexa and Roche/454 sequencing. Paired-end Solexa sequencing of genomic DNA to 85-fold coverage and an additional 10-fold coverage by single-end 454 sequencing resulted in ∼4 Gb of DNA sequence. Reads were assembled to a 40 Mb draft version (N50 of 117 kb) with the Velvet assembler. Comparative analysis with Neurospora genomes increased the N50 to 498 kb. The S. macrospora genome contains even fewer repeat regions than its closest sequenced relative, Neurospora crassa. Comparison with genomes of other fungi showed that S. macrospora, a model organism for morphogenesis and meiosis, harbors duplications of several genes involved in self/nonself-recognition. Furthermore, S. macrospora contains more polyketide biosynthesis genes than N. crassa. Phylogenetic analyses suggest that some of these genes may have been acquired by horizontal gene transfer from a distantly related ascomycete group. Our study shows that, for typical filamentous fungi, de novo assembly of genomes from short sequence reads alone is feasible, that a mixture of Solexa and 454 sequencing substantially improves the assembly, and that the resulting data can be used for comparative studies to address basic questions of fungal biology