Gift of Peace of Mind-The For yourself For your Family, 2000, Large Print Edition

The purpose of this booklet is to educate the public about advance directives. By doing so, we hope to increase the use of advance directives, as well as the quality and accuracy of the documents themselves. The reader is led through a series of steps that ultimately lead to filling out the advance directive documents in an informed manner.

Acvbp Versus Acvbp Plus Rituximab For Young Patients With Localized Low-Risk Diffuse Large B-Cell Lymphoma: A Study By The Groupe D'etude Des Lymphomes De L'adulte

Introduction: In a prior study, we demonstrated that ACVBP + consolidation was superior to 3 cycles of CHOP + radiotherapy in young patients (pts) with localized aggressive lymphoma (Reyes F et al. N Engl J Med 2005;352:1197). This randomized trial compared in these pts ACVBP vs. ACVBP + a short course of rituximab (R-ACVBP).Methods: untreated pts between 18 and 65y with stage I/II DLBCL and no adverse prognostic factors according to the aa-IPI were eligible. ACVBP consisted of 3 induction cycles given every 2 weeks: doxorubicin (75 mg/m2) day 1, cyclophosphamide (1.2g/m2) day 1, vindesine (2 mg/m2) day 1 and 5, bleomycin (10 mg) day 1 and 5, prednisone (60 mg/m2) day 1 to 5 followed by consolidation with metothrexate, ifosfamide, VP-16 and cytarabine. R-ACVBP consisted of the same regimen combined with 4 doses of rituximab (375 mg/m2) on day 1, 15, 29 and 43. Primary objective was EFS.Results: From 01/04 to 03/08, 223 pts were randomized, 113 in ACVBP and 110 in R-ACVBP arm. Characteristics were: median age 49y (18-65), stage I 63%, extranodal involvement 45%, bulky disease 4%. CR was 94% in ACVBP and 97% in ACVBP arm (ns). With a median follow-up of 43 months, the 3-y EFS was 82% (95% CI, 73% to 88%) in ACVBP and 93% (95% CI, 87% to 97%) in R-ACVBP group (P=0.0487). The 3-y PFS was 83% (95% CI, 74% to 89%) and 95% (95% CI, 89% to 98%) respectively (P=0.0205). OS did not significantly differ with a 3-y estimates of 97% (95% CI, 90% to 99%) for ACVBP and 98% (95% CI, 92% to 100%) for R-ACVBP (P=0.686). In multivariate analysis, a longer PFS was associated with R-ACVBP arm (P=0.0302) and lower b2-m level (P=0.0164). The same proportion of pts (27%) experienced at least 1 SAE in both groups. There were 4 deaths in each arm, with 1 treatment-related death in R-ACVBP (pneumocystis jiroveci pneumonia).Conclusion: the addition of only 4 doses of rituximab to ACVBP significantly improves EFS and PFS in younger pts with low-risk localized DLBCL.

Risk assessment of herbicide mixtures in a large European lake

Lake Geneva is one of the largest European lakes with a surface area of 580 km2. Its catchment area covers 7400 km2, of which approximately 20% is arable land. Monitoring campaigns have been carried out in 2004 and 2005 to determine the contamination of the lake by pesticides. The results highlight the widespread presence of herbicides in water, the measured concentrations for most substances remaining constant in 2004 and 2005. However, for some individual herbicides the concentrations increased drastically (e.g., the herbicide foramsulfuron). We assessed the environmental risk of the herbicides detected in the lake using water quality criteria recently determined for the Swiss environmental protection agency. Furthermore, we assessed the risk of herbicide mixtures, grouped based upon their mode of action. Generally, the risk estimated for all single substances is low, except for some sulfonylurea compounds. For these substances, the measured concentrations are higher than the predicted no-effect concentration. Impact on the flora of the lake can therefore not be excluded. When mixtures of pesticides with similar mode of action are taken into account, the risk remains lower than the mixture water quality criteria for all groups, but can reach as high as one third of this quality criteria. A further step would therefore be to assess the risk of the total pesticide mixture, including similar and dissimilar modes of action

A large deletion in the adRP gene PRPF31: evidence that haploinsufficiency is the cause of disease.

PURPOSE: To report a large deletion that encompasses more than 90% of PRPF31 gene and two other neighboring genes in their entirety in an adRP pedigree that appears to show only the typical clinical features of retinitis pigmentosa. METHODS: To identify PRPF31 mutation in a dominant RP family (ADRP2) previously linked to the RP11 locus, the 14 exons of PRPF31 were screened for mutations by direct sequencing. To investigate the possibility of a large deletion, microsatellite markers near PRPF31 gene were analyzed by non-denaturing PAGE. RESULTS: Initial screening of PRPF31 gene in the ADRP2 family did not reveal an obvious mutation. A large deletion was however suspected due to lack of heterozygosity for nearly all PRPF31 intragenic single nucleotide polymorphysm (SNPs). In order to estimate the size of the deletion, SNPs and microsatellite markers spanning and flanking PRPF31 were analyzed in the entire ADRP2 family. Haplotype analysis with the above markers suggested a deletion of approximately 30 kb that included the putative promoter region of a novel gene OSCAR, the entire genomic content of genes NDUFA3, TFPT and more than 90% of PRPF31 gene. Sequence analysis of the region flanking the potential deletion showed a high presence of Alu elements implicating Alu mediated recombination as the mechanism responsible for this event. CONCLUSIONS: This mutation provides evidence that haploinsufficiency rather than aberrant function of mutated proteins is the cause of disease in these adRP patients with mutations in PRPF31 gene.

Syndrome de l'intestin irritable: un diagnostic d'exclusion. [Irritable bowel syndrome: an exclusion diagnosis?].

The irritable bowel syndrome has been considered a diagnosis of exclusion and multiple diagnostic procedures were often performed in order to exclude an organic disorder. Nowadays, studies show that in young patients, who match the clinical criteria of irritable bowel syndrome and show no alarm features, the prevalence of underlying organic disorders is low, or at least not higher than in the general population. Based on these findings, current recommendations suggest that no extra diagnostic tests have to be performed in those patients, apart from the serological tests in search of celiac disease, which are recommended for patients presenting an irritable bowel syndrome with diarrhea or a mixed-type irritable bowel syndrome.

Latissimus dorsi muscle-flap over Gore-Tex patch for coverage of large thoracic defects in paediatric Ewing sarcoma.

Primary rib involvement accounts for 16% of paediatric Ewing sarcoma (ES). Neo-adjuvant chemotherapy and surgical tumor resection may leave large thoracic wall defects requiring complex reconstruction in a growing individual. We report our experience in three children aged 3, 10, and 12 years, in whom single-stage resection and reconstruction were performed using a Gore-Tex Dualmesh patch, covered by a latissimus dorsi rotation flap harvested in continuity with the thoracolumbar fascia. The youngest patient also had a vertical expandable prosthetic titanium rib (VEPTR) anchored to help prevent subsequent scoliosis throughout growth.

Stable isotope ecology of Miocene large mammals from Sandelzhausen, southern Germany

The carbon, oxygen, and strontium isotope composition of enamel from teeth of large Miocene herbivorous mammals from Sandelzhausen (MN5, late Early/early Middle Miocene) in the North Alpine foreland basin, were analyzed to infer diet and habitat. The mean enamel delta(13)C value of -11.4 +/- 1.0% (n = 53) for the nine taxa analyzed (including proboscideans, cervids, suids, chalicotheres, equids, rhinocerotids) indicates a pure C(3) plant diet for all mammals. (87)Sr/(86)Sr ratios of similar to 0.710 higher than those from teeth of the western Molasse Basin (0.708-0.709) seem to indicate preferential feeding of the mammals in the northeastern Molasse Basin. The sympatric herbivores have different mean delta(13)C and delta(18)O values which support diet partitioning and/or use of different habitats within a C(3) plant ecosystem. Especially the three sympatric rhinoceroses Plesiaceratherium fahlbuschi, Lartetotherium sansaniense, and Prosantorhinus germanicus show clear partitioning of plants and/or habitats. The palaeomerycid Germanomeryx fahlbuschi was a canopy folivore in moderately closed environments whereas Metaschizotherium bavaricum (Chalicotheriidae) and P. germanicus (Rhinocerotidae) were browsers in more closed forest environments. The horse Anchitherium aurelianense was probably a more generalized feeder than assumed from its dental morphology. The forest hog Hyotherium soemmeringi has the highest delta(13)C and lowest delta(18)O value of all analyzed taxa, possibly related to a frugivorous diet. Most taxa were water-dependent browsers that record meteoric water delta(18)O values of about -5.6 +/- 0.7% Vienna Standard Mean Ocean Water (VSMOW). Using a modern-day mean annual air temperature (MAT)-delta(18)OH(2)O relation a MAT of 19.3 +/- 1.5 degrees C can be reconstructed for Sandelzhausen. A Gomphotherium subtapiroideum tusk serially sampled for delta(18)O values does not record a clear pattern of seasonality. Thus most taxa were C(3) browsers in a forested and humid floodplain environment in the Molasse Basin, which experienced a warm-temperate to subtropical climate and possibly low seasonality.

Epidemiological characterization of Plasmodium falciparum in the Republic of Cabo Verde: implications for potential large-scale re-emergence of malaria

Background: Malaria has come near eradication at archipelago of Cabo Verde in 1970. Infections are now only observed in Santiago, where outbreaks occur. In these islands, malaria is considered by the international community as being of limited risk and, therefore, no prophylaxis is recommended. Since the understanding of factors that determine malaria outbreaks are crucial for controlling the disease, the present study aimed to investigate if the malaria infections observed in Santiago Island are maintained in isolated foci and in asymptomatic individuals.

Association of a common vitamin D-binding protein polymorphism with inflammatory bowel disease.

OBJECTIVE: Inflammatory bowel diseases (IBDs), Crohn's disease, and ulcerative colitis (UC), are multifactorial disorders, characterized by chronic inflammation of the intestine. A number of genetic components have been proposed to contribute to IBD pathogenesis. In this case-control study, we investigated the association between two common vitamin D-binding protein (DBP) genetic variants and IBD susceptibility. These two single nucleotide polymorphisms (SNPs) in exon 11 of the DBP gene, at codons 416 (GAT>GAG; Asp>Glu) and 420 (ACG>AAG; Thr>Lys), have been previously suggested to play roles in the etiology of other autoimmune diseases. METHODS: Using TaqMan SNP technology, we have genotyped 884 individuals (636 IBD cases and 248 non-IBD controls) for the two DBP variants. RESULTS: On statistical analysis, we observed that the DBP 420 variant Lys is less frequent in IBD cases than in non-IBD controls (allele frequencies, P=0.034; homozygous carrier genotype frequencies, P=0.006). This inverse association between the DBP 420 Lys and the disease remained significant, when non-IBD participants were compared with UC (homozygous carrier genotype frequencies, P=0.022) or Crohn's disease (homozygous carrier genotype frequencies, P=0.016) patients separately. Although the DBP position 416 alone was not found to be significantly associated with IBD, the haplotype DBP_2, consisting of 416 Asp and 420 Lys, was more frequent in the non-IBD population, particularly notably when compared with the UC group (Odds ratio, 4.390). CONCLUSION: Our study adds DBP to the list of potential genes that contribute to the complex genetic etiology of IBD, and further emphasizes the association between vitamin D homeostasis and intestinal inflammation.