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Objective: This study investigated mobile health enabled surveillance in ototoxicity. Method: This was a longitudinal study of 32 participants receiving chemotherapy. Baseline and exit audiograms that included conventional and extended high frequency audiometry were recorded within the patient's treatment venue using a validated mobile health audiometer. Results: Average hearing thresholds at baseline were within the normal range (81.2 per cent left; 93.8 per cent right), reducing at exit testing (71.9 per cent left; 78.1 per cent right). Half of participants presented with a threshold shift according to ototoxicity monitoring criteria. The frequencies affected the most were between 4000 and 16 000 Hz, with left ears significantly more affected than right ears. Noise levels exceeded the maximum permissible ambient noise levels in up to 43.8 per cent of low frequencies (250–1000 Hz). Conclusion: Mobile health supported audiometry proved to be an efficacious tool for ototoxicity monitoring at the treatment venue. Changes in hearing ability over time could be tracked, improving surveillance in patients with full treatment schedules. [ABSTRACT FROM AUTHOR]

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Aim The aims of this population genetics study of the common juniper across Eurasia were to (1) assess the contribution of southern mountain ranges to the post-glacial recolonization of high latitudes and (2) test whether recent expansion or high gene flow could explain the low genetic differentiation in Northern Eurasia. Location Northern Eurasia and mountain regions of Central Europe and Asia. Methods Six hundred and twenty-two individuals were sampled in 42 populations. Two chloroplast DNA (cp DNA) fragments were investigated ( trnT- trnL and 16S- trnA). Analyses of the distribution of haplotypes across the continent included a suite of phylogeographical and phylogenetic tests. Putative geographical distribution in the past was reconstructed using environmental niche modelling. Results Eighty-four haplotypes clustered into four main clades ( GL1- GL4). The largest clade, GL3, corresponds to populations from the Alps, northern Europe, Western Caucasus and Siberia. These populations were moderately differentiated (28%) compared to the total range (76%) and Fu's Fs statistic was negative, indicating a population expansion. Some haplotypes within GL3 form subclades with a restricted geographical distribution, suggesting a local origin of the mutation and limited dispersal. In line with these findings, modelling of ecological niches found no significant reduction in the expected range during the LGM. Remarkably, populations from the eastern part of North Caucasus, the Himalayas, Tien Shan and south Siberia were distinctly different from populations in the rest of the range. Main conclusions As in Siberian larch species, the pattern of genetic diversity at cp DNA across the natural range of J. communis suggests that colonization of northern Europe and Siberia started from a limited area and predated the last glaciation. It is likely that juniper survived the subsequent glacial epoch at high latitudes in cryptic refugia serving as secondary centres of recolonization. Southern mountain refugia contribution to the recolonization of high latitudes was, at best, limited. [ABSTRACT FROM AUTHOR]

Background:This study compared vestibulocollic reflex and vestibulo-ocular reflex functioning in subjects with and without human immunodeficiency virus. It also described test results throughout progression of the disease and compared the results of human immunodeficiency virus positive subjects who were receiving antiretroviral therapies with those not receiving this treatment.Methods:Subjects comprised 53 adults with human immunodeficiency virus (mean age 38.5 ± 4.4 years) and 38 without human immunodeficiency virus (mean age 36.9 ± 8.2 years). Clinical examinations included cervical vestibular-evoked myogenic potential and bithermal caloric testing.Results:Abnormal cervical vestibular-evoked myogenic potential and caloric results were significantly higher in the human immunodeficiency virus positive group (p = 0.001), with an odds ratio of 10.2. Vestibulocollic reflex and vestibulo-ocular reflex involvement increased with progression of the disease. There were more abnormal test results in subjects receiving antiretroviral therapies (66.7 per cent) than in those not receiving antiretroviral therapies (63.6 per cent), but this difference was insignificant.Conclusion:Human immunodeficiency virus seems to influence vestibulocollic reflex pathways. Combining cervical vestibular-evoked myogenic potential and caloric testing may be useful to detect early neurological involvement in human immunodeficiency virus positive subjects. [ABSTRACT FROM PUBLISHER]

Objective:To characterise auditory involvement secondary to excessive craniotubular bone growth in individuals with sclerosteosis in South Africa.Methods:This cross-sectional study assessed the auditory profile of 10 participants with sclerosteosis. An auditory test battery was used and results for each ear were recorded using descriptive and comparative analyses.Results:All participants presented with bilateral, mixed hearing losses. Of the 20 ears, hearing loss was moderate in 5 per cent (n = 1), severe in 55 per cent (n = 11) and profound in 40 per cent (n = 8). Air–bone gaps were smaller in older participants, although the difference was not statistically significant (p > 0.05). Computed tomography scans indicated pervasive abnormalities of the external auditory canal, tympanic membrane, middle-ear space, ossicles, oval window, round window and internal auditory canal. Narrowed internal auditory canals corresponded to poor speech discrimination, indicative of retrocochlear pathology and absent auditory brainstem response waves.Conclusion:Progressive abnormal bone formation in sclerosteosis involves the middle ear, the round and oval windows of the cochlea, and the internal auditory canal. The condition compromises conductive, sensory and neural auditory pathways, which results in moderate to profound, mixed hearing loss. [ABSTRACT FROM PUBLISHER]

Introduction:Disorders of the auditory and vestibular system are often associated with human immunodeficiency virus infection and acquired immunodeficiency syndrome. However, the extent and nature of these vestibular manifestations are unclear.Objective:To systematically review the current peer-reviewed literature on vestibular manifestations and pathology related to human immunodeficiency virus and acquired immunodeficiency syndrome.Method:Systematic review of peer-reviewed articles related to vestibular findings in individuals with human immunodeficiency virus infection and acquired immunodeficiency syndrome. Several electronic databases were searched.Results:We identified 442 records, reduced to 210 after excluding duplicates and reviews. These were reviewed for relevance to the scope of the study.Discussion:We identified only 13 reports investigating vestibular functioning and pathology in individuals affected by human immunodeficiency virus and acquired immunodeficiency syndrome. This condition can affect both the peripheral and central vestibular system, irrespective of age and viral disease stage. Peripheral vestibular involvement may affect up to 50 per cent of patients, and central vestibular involvement may be even more prevalent. Post-mortem studies suggest direct involvement of the entire vestibular system, while opportunistic infections such as oto- and neurosyphilis and encephalitis cause secondary vestibular dysfunction resulting in vertigo, dizziness and imbalance.Conclusion:Patients with human immunodeficiency virus and acquired immunodeficiency syndrome should routinely be monitored for vestibular involvement, to minimise functional limitations of quality of life. [ABSTRACT FROM PUBLISHER]

The use of admixed human populations to scan the genome for chromosomal segments affecting complex phenotypic traits has proved a powerful analytical tool. However, its potential in other organisms has not yet been evaluated. Here, we use DNA microsatellites to assess the feasibility of this approach in hybrid zones between two members of the ‘model tree’ genus Populus: Populus alba (white poplar) and Populus tremula (European aspen). We analyzed samples of both species and a Central European hybrid zone (N=544 chromosomes) for a genome-wide set of 19 polymorphic DNA microsatellites. Our results indicate that allele frequency differentials between the two species are substantial (mean δ=0.619±0.067). Background linkage disequilibrium (LD) in samples of the parental gene pools is moderate and should respond to sampling schemes that minimize drift and account for rare alleles. LD in hybrids decays with increasing number of backcross generations as expected from theory and approaches background levels of the parental gene pools in advanced generation backcrosses. Introgression from P. tremula into P. alba varies strongly across marker loci. For several markers, alleles from P. tremula are slightly over-represented relative to neutral expectations, whereas a single locus exhibits evidence of selection against P. tremula genotypes. We interpret our results in terms of the potential for admixture mapping in these two ecologically divergent Populus species, and we validate a modified approach of studying genotypic clines in ‘mosaic’ hybrid zones.Heredity (2007) 98, 74–84. doi:10.1038/sj.hdy.6800898; published online 20 September 2006 [ABSTRACT FROM AUTHOR]

Here we present the work of the 2006 University of Arizona team in the iGEM (international Genetically Engineered Machine) competition sponsored by MIT. Our aim was to develop an inducible water colour system for painting bacteria in three colours. Using BioBricks, a plasmid was designed for insertion into E. coli which would allow the bacterium to respond to each of three different chemical inducers by producing yellow, cyan or red fluorescent proteins. In principle the inducers could be deposited on a bacterial lawn using a high-resolution printer so that three colour images could be produced with a spatial resolution matching the size of the bacterium. This could be the first step towards producing a bacterial lawn that behaves like a canvas for watercolour painting or eventually a three-colour television set. The application connects with current interest in precise control of cellular response desired in biosensors and bioengineered materials. The University of Arizona iGEM team called the ‘Cell Raisers’ was assembled in May 2006 and worked enthusiastically throughout the summer. The team was comprised of six undergraduates (Tyler Brown, Brian Heinze, Patrick Hollinger, Josh Kittleson, Kevin MacDow, and Dan Reavis), one graduate student (Carlos Chang), and two faculty members (Joan Curry and Mark Riley). This proved to be an ambitious project, and while the final goal was not fully realised, first steps were made in terms of design, plasmid construction and bacterial deposition with an inkjet printer. Patrick Hollinger and Brian Heinze gave the technical presentation to judges and competing teams on Saturday, November 4, 2006 in MIT's Stata Center. The team also presented a poster that was viewed in the evening after all the presentations. For their efforts, the University of Arizona team received honourable mention with special consideration: ‘For progress toward synthetic biology in three colours’. [ABSTRACT FROM AUTHOR]

The effects of different buffer structures on the avalanche and post avalanche behaviour of high voltage silicon diodes under high reverse current conditions has been investigated. After the onset of avalanche, when the diodes are reverse biased, branches both with positive and negative differential resistance may occur in the device characteristics and depend sensitively on the doping profile of the buffer layer. By numerical device simulation the influence of relevant bulk doping and various buffer profiles on these static reverse characteristics are analysed to understand, clarify and illustrate the breakdown behaviour of high voltage pin-diodes. Based upon these considerations an effective restriction of the electric field maximum at the nn+-junction at the cathode side of the diode can be achieved by adapting the doping gradient of the buffer profile. [ABSTRACT FROM AUTHOR]

The renewed interest in the use of hybrid zones for studying speciation calls for the identification and study of hybrid zones across a wide range of organisms, especially in long-lived taxa for which it is often difficult to generate interpopulation variation through controlled crosses. Here, we report on the extent and direction of introgression between two members of the‘model tree’ genusPopulus:Populus alba(white poplar) andPopulus tremula(European aspen), across a large zone of sympatry located in the Danube valley. We genotyped 93 hybrid morphotypes and samples from four parental reference populations from within and outside the zone of sympatry for a genome-wide set of 20 nuclear microsatellites and eight plastid DNA restriction site polymorphisms. Our results indicate that introgression occurs preferentially fromP. tremulatoP. albaviaP. tremulapollen. This unidirectional pattern is facilitated by high levels of pollen vs. seed dispersal inP. tremula(pollen/seed flow = 23.9) and by great ecological opportunity in the lowland floodplain forest in proximity toP. albaseed parents, which maintains gene flow in the direction ofP. albadespite smaller effective population sizes (N e) in this species (P. alba N e c.500–550;P. tremula N e c.550–700). Our results indicate that hybrid zones will be valuable tools for studying the genetic architecture of the barrier to gene flow between these two ecologically divergentPopulusspecies. [ABSTRACT FROM AUTHOR]

Bone marrow fibrosis (MF) has been shown to indicate therapy failure in Ph+ chronic myeloid leukemia (CML). However, the results on the development of MF during interferon-a therapy of CML are controversial. The significance of the interferon dose has not been considered as yet. In total, 627 bone marrow biopsies taken prospectively from 200 patients with CML recruited in two studies using different doses of interferon-a ± low-dose cytosine arabinoside were examined for MF before and during therapy. The results showed that the risk of MF depended significantly on the interferon-a dose applied (P<0.000005). MF progressed during low-dose therapy (3 × 5 × 106?IU/week), but was prevented from progression when applying high dose (5 × 106?IU/m2/per day). MF disappeared when high-dose interferon-a was combined with low-dose cytosine arabinoside (P<0.000005). The risk of death markedly increased when MF occurred or progressed (P<0.0009), independent of all other prognostic factors evaluated including the cytogenetic response. In conclusion, the effectiveness of interferon-a on MF depends on the treatment intensity. MF reverses when combining high-dose interferon-a with low-dose cytosine arabinoside, but progresses when applying low-dose interferon-a. MF appears to be a significant early indicator of ineffective therapy in CML.Leukemia (2004) 18, 1460-1467. doi:10.1038/sj.leu.2403451 Published online 29 July 2004 [ABSTRACT FROM AUTHOR]

Marrow fibrosis (MF) has rarely been considered in therapy studies on chronic myeloid leukemia (CML), and there is a lack of long-term observations on the basis of sequential bone marrow biopsies (BMBs) taken prospectively during the course of disease. A total of 848 BMBs from 400 patients with Ph+ CML recruited in the German randomized CML study I were examined for MF before and during therapy. In total, 110 patients had been randomized to receive interferon (IFN)-a, and 290 to receive chemotherapy (hydroxyurea (HU): 154, busulfan: 136). During IFN-a and HU medication, MF was reduced or did not increase for about 2 years. Evolving or progressive MF was an independent and early predictor of therapy failure about 2 years earlier than indicated by changes in the peripheral blood, spleen size, marrow blast count and cytogenetics (P<0.00005), resulting in a significant shortening of the survival times of patients independent of the type of therapy applied including allografting (multivariate analyses; P<0.00005). The analyzed long-term observations strongly indicate that MF is an independent poor prognostic complication of CML, allowing an early prediction of therapy failure. Consideration of the fiber content in marrow may therefore significantly improve the prediction of therapy efficacy and outcome of disease.Leukemia (2003) 17, 2444-2453. doi:10.1038/sj.leu.2403172 Published online 16 October 2003 [ABSTRACT FROM AUTHOR]

Chronic myeloid leukemia (CML) in older patients has not been studied well. To assess the long-term outcome of older patients with Philadelphia- and/or BCR-ABL-positive CML, 199 patients aged ?60 years representing 23% of 856 patients enrolled in the German randomized CML-studies I (interferon a (IFN) vs hydroxyurea (HU) vs busulfan (BU) and II (IFN+HU vs HU alone) were analyzed after a median observation time of 7 years. In all, 45 patients were treated with Bu, 63 with HU, and 91 with IFN. The 5-year survival was 38% in patients ?60 years and 47% in patients <60 years (P<0.001). Whereas 5-year survival in chemotherapy-treated older patients was inferior to that in younger patients (33 vs 46%, P=0.006 for HU and 29 vs 38%, P=0.042 for Bu), no significant survival difference could be verified in IFN-treated patients (46 vs 53%, P=0.077). Calculation of age-adjusted, relative survival confirmed these results. Adverse effects of IFN were similar in both age groups, but IFN dosage to achieve treatment goals was lower in older patients. We conclude that the course of CML is not different in the elderly. They require lower IFN doses, achieve the same hematologic and cytogenetic response rates and the same survival advantage at comparable toxicity.Leukemia (2003) 17, 1820-1826. doi:10.1038/sj.leu.2403042 [ABSTRACT FROM AUTHOR]

Due to eligibility criteria not all patients with the disease under investigation can be recruited for therapeutic studies. Thus, the external validity of study results cannot per se be taken for granted. The representativity of the admitted patients is the most relevant determinant for external validity and has to be assessed. As an example we examined the representativity of the patients recruited for the German multicenter study group for adult acute lymphoblastic leukemia (ALL) (GMALL). Lacking nationwide ALL incidence figures available in Germany, a methodology was developed to estimate incidence figures, too. All relevant study groups, hospitals, and diagnostic labs were asked to provide data about patients with ALL newly diagnosed between 1997 and 1998. A matching procedure was developed, as heterogeneous databases had to be pooled and checked for duplicates. Age- and sex-specific incidences of ALL were estimated and compared with the number of patients recruited for the GMALL in the same time period. The purpose was to develop a methodology for estimating incidence figures and evaluating the representativity of patients of the GMALL. The combination of various data sources allowed estimation of reliable incidence data for ALL in Germany. Comparisons with the incidence figures for ALL in other countries and crosschecks within Germany confirm our results. Sixty-two percent of all ALL patients in Germany were admitted to the GMALL study. The recruitment rate of more than 60% of the annual incidence of ALL to the GMALL suggests a high external validity as well as an impact of the study on the patterns of treatment and referral of ALL in adults in Germany. There is no selection bias of patients admitted to the GMALL compared to those patients not included in the study. [ABSTRACT FROM AUTHOR]

The reliability of routine BCR-ABL RT-nested-PCR was evaluated in 1453 B-lineage ALL or hybrid leukemia at initial diagnosis by RT-nested-PCR. All BCR-ABL-positive (n = 642) and 176 BCR-ABL-negative samples underwent a second RT-PCR. In 518 patients, karyotyping and/or FISH was compared to the BCR-ABL status. The second RT-PCR revealed in 155/642 initially positive samples a divergent result (153 BCR-ABL-negative, two other transcripts) that in most cases turned out to be caused by contaminations in the first RT-nested-PCR. Confirmatory RT-PCR detected 2/176 false negative first RT-nested-PCR results. Thirty-nine specimens remained ambiguous despite different RT-PCR approaches. As far as cytogenetic evaluation and FISH is available (n = 23), the majority but not all patients with an ambiguous RT-PCR result were Ph-negative (n = 18). RT-nested-PCR and cytogenetics yielded in 346 of 383 evaluable samples a concordant result. Differing results are given and account in part to the lower sensitivity of karyotyping. Taken together, confirmed RT-PCR detected BCR-ABL fusion transcripts consistently in 487 out of 1453 ALL samples (c-ALL: 43%, pre-B ALL: 34%, pro-B ALL: 5%, B-ALL: 0%, hybrid leukemia: 5/11). Since false positive initial RT-nested-PCR data were frequent, either confirmatory second RT-PCR or FISH analysis is warranted to guarantee sensitive and reliable results of utmost clinical relevance. [ABSTRACT FROM AUTHOR]

The reliability of routine BCR-ABL RT-nested-PCR was evaluated in 1453 B-lineage ALL or hybrid leukemia at initial diagnosis by RT-nested-PCR. All BCR-ABL-positive (n = 642) and 176 BCR-ABL-negative samples underwent a second RT-PCR. In 518 patients, karyotyping and/or FISH was compared to the BCR-ABL status. The second RT-PCR revealed in 155/642 initially positive samples a divergent result (153 BCR-ABL-negative, two other transcripts) that in most cases turned out to be caused by contaminations in the first RT-nested-PCR. Confirmatory RT-PCR detected 2/176 false negative first RT-nested-PCR results. Thirty-nine specimens remained ambiguous despite different RT-PCR approaches. As far as cytogenetic evaluation and FISH is available (n = 23), the majority but not all patients with an ambiguous RT-PCR result were Ph-negative (n = 18). RT-nested-PCR and cytogenetics yielded in 346 of 383 evaluable samples a concordant result. Differing results are given and account in part to the lower sensitivity of karyotyping. Taken together, confirmed RT-PCR detected BCR-ABL fusion transcripts consistently in 487 out of 1453 ALL samples (c-ALL: 43%, pre-B ALL: 34%, pro-B ALL: 5%, B-ALL: 0%, hybrid leukemia: 5/11). Since false positive initial RT-nested-PCR data were frequent, either confirmatory second RT-PCR or FISH analysis is warranted to guarantee sensitive and reliable results of utmost clinical relevance. [ABSTRACT FROM AUTHOR]

Conserved chloroplast (cp) DNA primer pairs are useful in plant molecular genetics, evolution and ecology. We have designed 20 conserved cpDNA primer pairs that, in combination with 18 previously described ones, amplify overlapping fragments (mean size of 2.5 kb) spanning the large single copy (LSC) region from Eudicots. These 38 primer pairs as well as eight primer pairs flanking cpDNA microsatellites were tested on 20 plant species belonging to 13 families. At least 79% and up to 100% of the LSC (> 86 kb) can be amplified. Many primer pairs are robust and work with all species. [ABSTRACT FROM AUTHOR]

We present an approach to infer the number of pollen donors directly from genotype data of open- pollinated progeny of Quercus robur (pedunculate oak), a highly outcrossing tree species. The approach is based on closely linked, highly polymorphic codominant microsatellite markers. Initially the close linkages between three previously mapped microsatellite loci were confirmed by studies of linkage disequilibrium (LD). Then an approach to track the pollen donors contributing to maternal half-sib families (open-pollinated families) was developed by analysing haplotype arrays of closely linked microsatellite markers transmitted from the fathers to the progeny. Simulated data of five linked microsatellite loci segregating in eight open-pollinated families were used to study the relationship between the number of paternal chromosomes detected by this ”haplotype approach” and the number of diploid fathers contributing to the families. The results showed that the number of diploid pollen donors can be expressed as an exponential function of the number of paternal chromosomes inferred from the progeny. The 95% confidence interval of this regression function is used to determine the minimum number of fathers contributing to a genotyped open-pollinated family of Quercus robur. Finally this open-pollinated family is used to demonstrate the resolution obtained with the ”haplotype approach”. Six independent microsatellite loci were used to study relatedness among all pairs of pollen gametes that share a haplotype of three linked markers. The results suggest that the majority of such gametes are identical by descent from the same father. The ”haplotype approach” presented here can be used to monitor the number of contributing pollen donors in commercial seedlot samples from oak or any other outcrossing tree species for which closely linked, highly polymorphic, codominant genetic markers are available. [ABSTRACT FROM AUTHOR]

Purpose : The detection of long-term persistent chromosome aberrations in circulating haemopoietic stem cells after accidental radiation exposure. Materialand methods : Peripheral blood samples fromhighly exposed persons were collected 7-25 years after the radiation accidents in Moscow (1971), Kazan (1975) and Chernobyl (1996). Haemopoietic blood stem cells were analysed when investigating individual colonies derived from haemopoietic progenitor cells: burst-forming units-erythroid (BFU-E), granulocytemacrophage-colony-forming cells (GM-CFC) and multipotent granulocyte-erythrocyte-macrophage-megakaryocyte-colonyforming cells (GEMM-CFC). Colony formation was obtained in methylcellulose cultures. Chromosome preparations in single colonies were performed using a microtechnique. Results : Nine patients were investigated at 1 to 4 follow-up time points after radiation exposure. Three hundred and thirty-four single colonies were analyzed resulting in 1375 mitoses. It was found that colonies showed chromosome aberrations (ChA) up to 25 years after radiation exposure by classical cytogenetics and by fluorescence in situ hybridization (FISH). Stable aberrations were detected in 21% of colonies. They were clonal in 19% of colonies, i.e. the same abnormality was found in all cells derived from a single colony. In 2% of colonies ChA were stable but non-clonal; unstable ChA were not observed. Conclusions : The results indicate that blood-derived haemopoietic stem cells may serve as a biological indicator to detect radiation-induced ChA. Since they are considered to be in dynamic and functional exchange with stem cells in the medullary sites of blood cell formation such as bone marrow, the use of blood stem cells as a marker of radiation effects should be explored to assess the repair status of the stem cell pool as such. [ABSTRACT FROM AUTHOR]

Microsatellites were used for genetic analysis of maternal half-sib families of Quercus robur, pedunculate oak, a highly outcrossing tree species. A model half-sib family including the mother tree and 28 offspring individuals as well as samples from six single tree harvests from a forestry company, 4–8 individuals each, were genotyped at 9 microsatellite loci. No prior information about the genotypes of the mother trees were available for these six seedlot samples. Analysis of the model half-sib family revealed that the maternal genotypes can be inferred from the offspring genotypes due to codominant Mendelian inheritance of the microsatellites. Analysis of the single tree harvests, supplied as six maternal half-sib families, revealed contaminations with unrelated seedlings in four out of six cases. Average relatedness between the remaining individuals indicated that they were indeed half-sibs, probably with a proportion of full-sibs among them. For five samples the genotypes of the mother trees were partially inferred from the offspring genotypes. The supposed number of five different mother trees was confirmed by direct comparison of the maternal genotypes and by pairwise FST calculations between families. We show that correct genotype reconstruction can be confirmed by monitoring recombination events between linked markers. Our results demonstrate that microsatellite analysis is a suitable means to approach two key problems of legal regulations on the marketing of seed material from pedunculate oak: the number of trees included in seed harvests and the detection of seed contaminations. [ABSTRACT FROM AUTHOR]

Nine previously untreated patients with Philadelphia chromosome-positive chronic myelocytic leukemia (CML) were treated with recombinant interferon alpha 2a (rIFN-alpha 2a) and hydroxyurea. Patients received 6×10 U rIFN-alpha 2a daily for the first week and 3×10 U rIFN-alpha 2a daily for the second week. As maintenance treatment starting on day 15, patients received 3×10 U rIFN-alpha 2 a 3 times a week. Simultaneously, hydroxyurea was given, starting at a dose of 40 mg/kg on day one. The maintenance dosage was adjusted to the white blood cell count. Two patients responded with complete hematological remissions but without cytogenetic and molecular-genetic improvements. Seven patients responded with partial hematological remissions. Response to therapy was rapid; normal white blood cell counts were reached after a median of 12 days. The doses of rIFN-alpha 2a and hydroxyurea needed to keep the leucocyte count in the normal range were low (3×10 U rIFN-alpha 2a 3 times per week, 0.5-1.5 g hydroxyurea/day). Acute toxicity of the combination therapy consisted of fever (9 of 9 patients), flulike symptoms (7 of 9 patients), pruritus and/or rash (3 of 9 patients) and evidence of a tumor cell lysis syndrome (1 of 9 patients). The side effects were not dose-limiting. Combination therapy with rIFN-alpha 2a and hydroxyurea for CML is well tolerated and allows quick and effective hematological control of the disease. [ABSTRACT FROM AUTHOR]

We have studied the clinical courses of 69 patients with blastic crises of Philadelphia chromosome positive CML to identify parameters that were associated with an increased response rate or survival. Cytogenetic analysis at the time of blastic transformation revealed additional chromosome changes in 70% of the patients tested. Bone marrow fibrosis was detected in 58% of evaluable patients. Lymphoblastic transformation was seen in 28% of the patients tested with cell surface marker analysis. The value of 5'-nucleotidase as a marker for distinguishing lymphoid from non-lymphoid blast crisis was confirmed. Of 57 evaluable patients, 23 (40%) responded to therapy (CR/PR longer than 14 days). Median survival was 75 days. Longer survival was related to the following factors: Ph-chromosome as the only detectable cytogenetic abnormality; lymphoblastic transformation; no bone marrow fibrosis; high percentage of blasts and promyelocytes in the bone marrow, and response to therapy. No prognostic significance was associated with age, sex, Tdt, LDH, spleen size, duration of the chronic phase of the disease, white blood cell count, Hb, platelet count and percentages of basophils, eosinophils, erythroblasts and blasts and promyelocytes in the peripheral blood. These data confirm the poor prognosis of patients with blastic crisis of CML treated by conventional chemotherapy. [ABSTRACT FROM AUTHOR]

Ninety patients with Philadelphia chromosome-positive chronic myelogenous leukemia in blast crisis were reviewed to identify significant prognostic associations. At diagnosis of blast crisis the main clinical, laboratory, and cytogenetic data were recorded and evaluated for prognostic significance. At the time of the analysis 89 patients had died, with a median survival of 11 weeks from diagnosis of blast crisis. Patient characteristics demonstrated in the univariate analysis to have significant association with shorter survival were: thrombocythemia, leukocyte count above 20 x 10(9), Karnofsky index < 50%, nonlymphoid blast cell morphology, cytogenetic clonal evolution, the presence of a double Philadelphia chromosome or trisomy 8, and no response to therapy. In 17 of 59 patients (29%) evaluable for response to therapy a complete or partial remission was achieved. These responders had a significantly longer median survival (25 weeks) as compared with nonresponders (9 weeks). Response to therapy was significantly better in lymphoid blast crisis and in patients without clonal evolution. In a multivariate analysis containing all significant variables of the univariate analysis two parameters retained their prognostic significance: response to therapy and trisomy 8. In spite of the short overall survival in blast crisis, the determination of prognostic factors may be a useful tool for the clinician planning therapy, especially new therapeutic approaches. [ABSTRACT FROM AUTHOR]

The article presents a commentary on the study "Association genetics in Pinus taeda L. II. Carbon isotope discrimination," by S. C. González-Martínez and colleagues. According to the author, the paper provides partly an answer to the query about the strong clinical and ecotypic variation in the growth traits of forest trees since the first genetic markers became available. The researchers, accordingly, show how two particular nucleotide changes influence drought tolerance in pines.

A correction to the article "Admixture in European Populus Hybrid Zones Makes Feasible the Mapping of Loci that Contribute to Reproductive Isolation and Trait Differences" that was published in the September 20, 2006 issue is presented.