Ocean acidification and marine trace gas emissions

The oceanic uptake of man-made CO₂ emissions is resulting in a measureable decrease in the pH of the surface oceans, a process which is predicted to have severe consequences for marine biological and biogeochemical processes [Caldeira K, Wickett ME (2003) Nature 425:365; The Royal Society (2005) Policy Document 12/05 (Royal Society, London)]. Here, we describe results showing how a doubling of current atmospheric CO₂ affects the production of a suite of atmospherically important marine trace gases. Two CO₂ treatments were used during a mesocosm CO₂ perturbation experiment in a Norwegian fjord (present day: ∼380 ppmv and year 2100: ∼750 ppmv), and phytoplankton blooms were stimulated by the addition of nutrients. Seawater trace gas concentrations were monitored over the growth and decline of the blooms, revealing that concentrations of methyl iodide and dimethylsulfide were significantly reduced under high CO_2. Additionally, large reductions in concentrations of other iodocarbons were observed. The response of bromocarbons to high CO₂ was less clear cut. Further research is now required to understand how ocean acidification might impact on global marine trace gas fluxes and how these impacts might feed through to changes in the earth''s future climate and atmospheric chemistry.     

Phenotypic and clinical heterogeneity of CD56-positive acute nonlymphoblastic leukemia

Summary The precise phenotype and clinical course are described of a subgroup of acute nonlymphoblastic leukemias (ANLL) expressing the NK-cell differentiation antigen CD56. As previously reported, CD56+ leukemias occurred in a frequency of about 20% of ANLL cases showing clinical and immunophenotypical heterogeneity. Carrying various myelomonocytic markers, all cases were diagnosed to be of nonlymphoid origin. Positive or negative expression of CD34 allowed us to distinguish two major subtypes of CD56+ leukemias representing immature and more differentiated cells carrying further differentiation antigens (CD14 and/or CD15) of the myelomonocytic lineages. These phenotypes correlated with the M0, M2, M4, and M5 leukemias of the FAB classification.     

High-dose cytosine arabinoside and daunorubicin postremission therapy in adults with de novo acute myeloid leukemia

A total of 149 consecutive de novo AML patients aged 50 years or less (median age = 37 years) were enrolled in this prospective multicenter trial initiated in May 1985. All patients received the same induction and early consolidation therapy with daunorubicin (DNR), cytosine arabinoside (Ara-C), and etoposide (DAV). High-dose Ara-C/DNR therapy included Ara-C at 3 g/m², in 12 doses (HD-Ara-C/DNR I) and eight doses (HD-Ara-C/DNR II), followed by DNR 30 mg/m² for 3 days. A complete remission (CR) was achieved in 104 (70%) patients; 61 complete responders received at least one cycle with HD-Ara-C/DNR. If those patients who were transplanted in first CR (n=26), were not considered, the median relapsefree-survival (MRFS) of the remaining 78 patients was 15 months, with a probability of relapse-free survival (RFS) at 116 months of 30% (95% CI, 20–40%) after a median follow-up of 95 months. The MRFS of the HD-Ara-C/DNR consolidated patients was 25 months, with a probability of RFS at 116 months of 37% (95% CI, 24–50%). If all patients who were transplanted (n=44) were not considered, the median survival time (MST) was 18 months with a probability of being alive at 118 months of 24% (95% CI, 16–33%). MST of the HD-Ara-C/DNR consolidated patients was 58 months with a survival probability of 46% (95% CI, 31–60%) at 118 months. Prognostic factor analysis did not reveal any significant influence of age, sex, FAB subtype, white blood cell count, hemoglobin level, thrombocyte count, LDH, or response to the first induction course on RFS of the HD-Ara-C/DNR consolidated patients. In summary, HD-Ara-C/DNR consolidation can improve the long-term outcome of a subgroup of de novo AML patients. Further improvement of the outcome seems to depend on the identification of patients with an inferior outcome under that strategy who might benefit from alternative treatment strategies.     

Intravenous delivery of cysteamine for the treatment of cystinosis: association with hepatotoxicity

Nephropathic cystinosis is a lysosomal storage disorder, which, if untreated, results in renal failure by age 10 years. Oral cysteamine has been shown to preserve renal function in these patients. In this study, a 2-year-old girl with nephropathic cystinosis and severe gastrointestinal dysmotility was treated with intravenous (i.v.) administration of cysteamine hydrochloride (HCl). This is only the second report of long-term i.v. cysteamine therapy for nephropathic cystinosis. Unlike the treatment in the previous case, however, treatment in our patient was limited by liver toxicity.     

Mutation and association analyses of the candidate genes ESR1, ESR2, MAX, PCNA, and KAT2A in patients with unexplained MSH2-deficient tumors

Lynch syndrome (Hereditary non-polyposis colorectal cancer/HNPCC) is a cancer susceptibility syndrome which is caused by germline mutations in DNA mismatch repair (MMR) genes, in particular MLH1 and MSH2. A pathogenic germline mutation in the respective MMR gene is suggested by the finding of a loss of a mismatch repair protein in tumor tissue on immunohistochemical staining combined with an early age of onset and/or the familial occurrence of colorectal cancer. Pathogenic germline mutations are identifiable in around 60% of patients suspected of Lynch syndrome, depending on the familial occurrence. The aim of the present study was to identify novel susceptibility genes for Lynch syndrome. 64 Healthy controls and 64 Lynch syndrome patients with no pathogenic MSH2 mutation but a loss of MSH2 expression in their tumor tissue were screened for rare and disease causing germline mutations in the functional candidate genes ESR1, ESR2, MAX, PCNA, and KAT2A. Thirty variants were identified, and these were then genotyped in an independent sample of 36 mutation negative Lynch syndrome patients and 234 controls. Since a trend towards association was observed for KAT2A, an additional set of 21 tagging SNPs was analyzed at this locus in a final case-control sample of 142 mutation negative Lynch syndrome patients and 298 controls. The mutation analysis failed to reveal any rare disease-causing mutations. No association was found at the single-marker or haplotypic level for any common disease-modifying variant. The present results suggest that neither rare nor common genetic variants in ESR1, ESR2, MAX, PCNA, or KAT2A contribute to the development of Lynch syndrome.     

An examination of subgroup classification in irritable bowel syndrome patients over time: a prospective study

BACKGROUND: Irritable bowel syndrome (IBS) is a complex functional gastrointestinal disorder which to date remains poorly understood. Therapies for irritable bowel syndrome (IBS) patients are usually aimed at relieving the predominant symptom; however, little evidence exists as to whether or not the predominant symptom changes with time. Nurses are becoming increasingly involved in the assessment and management of IBS patients. OBJECTIVES: To categorise IBS patients into one of three sub-types, namely diarrhoea-predominant, constipation-predominant and a third group who alternate between the two, and to investigate changes in patient sub-type classification over time. DESIGN: Observational cohort study. SETTING: The general population of the United Kingdom (UK). METHODS: A cohort of 494 IBS patients, with a confirmed Rome II classification diagnosis, was recruited in the UK. Patients' IBS symptoms were recorded throughout a 26-week period. Proportions of individuals in each IBS subgroup were calculated and probabilities of moving from one subgroup to another between consecutive weeks were estimated. RESULTS: The percentage of patients given an overall subgroup classification of diarrhoea-predominant IBD (D-IBS) is 40.9%; 58.1% and 1% were classified as belonging to the alternator (A-IBS) and constipation-predominant (C-IBS) subgroups, respectively. PATIENTS: classified as an alternator or as diarrhoea-predominant have a high probability (0.67 and 0.71, respectively) of remaining in the same subgroup; however this probability is lower for constipation-predominant patients (0.35). CONCLUSION: Although many patients remain in the same IBS subgroup classification over time, there are individuals whose subgroup classification varies. As such, patients' IBS subgroup classification should be reviewed regularly and treatment adjusted accordingly in order to optimise patient care.