ABSTRACT
BACKGROUND: The reported incidence of Philadelphia-negative myeloproliferative neoplasms (MPNs) differs substantially between previous reports, likely due to true regional differences in incidence and/or variations in the quality and coverage of the cancer registers. OBJECTIVE: We therefore assessed MPN incidence in Sweden during recent years using prospectively collected information captured in Swedish health registers. METHODS: Patients with MPNs were identified through the Swedish Cancer Register and Swedish Blood Cancer Register between 2000 and 2014. Information on the Swedish population was obtained from the Human Mortality Database. Crude and age-standardized incidence rates of MPNs with 95% confidence intervals (CIs) were calculated. RESULTS: A total of 6281 MPN cases were reported to the Swedish Cancer Register and Swedish Blood Cancer Register during 2000-2014. The age-standardized, to the Swedish population in 2000, incidence for all MPNs was 4.45 (95% confidence interval [CI] 4.34-4.56)/100 000 person-years. The age-standardized incidence for polycythemia vera was 1.48 (1.42-1.54), for essential thrombocythemia 1.60 (1.53-1.66) and for primary myelofibrosis 0.52 (0.48-0.56)/100 000 person-years, respectively. The incidence rate of MPNs was substantially higher in the older compared to the younger age groups. The incidence increased during the study period, likely to do better reporting and increasing age of the general population. CONCLUSION: The reported MPN incidences in our study, which were in the higher interval of previously published studies, are likely more accurate compared to previous reports due to the population-based setting and high level of coverage in the Swedish Cancer and Blood Cancer Registers.
Subject(s)
Bone Marrow Neoplasms/epidemiology , Adolescent , Adult , Age Factors , Aged , Aged, 80 and over , Female , Humans , Incidence , Male , Middle Aged , Polycythemia Vera/epidemiology , Primary Myelofibrosis/epidemiology , Prospective Studies , Registries , Sweden/epidemiology , Thrombocythemia, Essential/epidemiology , Young AdultABSTRACT
BACKGROUND: Drowning leading to out-of-hospital cardiac arrest (OHCA) and death is a major public health concern. Submersion with duration of less than 10min is associated with favorable neurological outcome and nearby bystanders play a considerable role in rescue and resuscitation. Drones can provide a visual overview of an accident scene, their potential as lifesaving tools in drowning has not been evaluated. AIM: The aim of this simulation study was to evaluate the efficiency of a drone for providing earlier location of a submerged possible drowning victim in comparison with standard procedure. METHOD: This randomized simulation study used a submerged manikin placed in a shallow (<2m) 100×100-m area at Tylösand beach, Sweden. A search party of 14 surf-lifeguards (control) was compared to a drone transmitting video to a tablet (intervention). Time from start to contact with the manikin was the primary endpoint. RESULTS: Twenty searches were performed in total, 10 for each group. The median time from start to contact with the manikin was 4:34min (IQR 2:56-7:48) for the search party (control) and 0:47min (IQR 0:38-0:58) for the drone-system (intervention) respectively (p<0.001). The median time saved by using the drone was 3:38min (IQR 2:02-6:38). CONCLUSION: A drone transmitting live video to a tablet is feasible, time saving in comparison to traditional search parties and may be used for providing earlier location of submerged victims at a beach. Drone search can possibly contribute to earlier onset of CPR in drowning victims.
Subject(s)
Aircraft , Drowning , Emergency Medical Services/methods , Geographic Information Systems/instrumentation , Out-of-Hospital Cardiac Arrest/therapy , Time Factors , Cardiopulmonary Resuscitation , Computer Simulation , Humans , Manikins , Mobile Applications , Out-of-Hospital Cardiac Arrest/etiology , Prospective Studies , Random AllocationABSTRACT
The discovery of somatic mutations, primarily JAK2V617F and CALR, in classic BCR-ABL1-negative myeloproliferative neoplasms (MPNs) has generated interest in the development of molecularly targeted therapies, whose accurate assessment requires a standardized framework. A working group, comprised of members from European LeukemiaNet (ELN) and International Working Group for MPN Research and Treatment (IWG-MRT), prepared consensus-based recommendations regarding trial design, patient selection and definition of relevant end points. Accordingly, a response able to capture the long-term effect of the drug should be selected as the end point of phase II trials aimed at developing new drugs for MPNs. A time-to-event, such as overall survival, or progression-free survival or both, as co-primary end points, should measure efficacy in phase III studies. New drugs should be tested for preventing disease progression in myelofibrosis patients with early disease in randomized studies, and a time to event, such as progression-free or event-free survival should be the primary end point. Phase III trials aimed at preventing vascular events in polycythemia vera and essential thrombocythemia should be based on a selection of the target population based on new prognostic factors, including JAK2 mutation. In conclusion, we recommended a format for clinical trials in MPNs that facilitates communication between academic investigators, regulatory agencies and drug companies.
Subject(s)
Consensus , Endpoint Determination , Fusion Proteins, bcr-abl/genetics , Myeloproliferative Disorders/drug therapy , Humans , Myeloproliferative Disorders/genetics , PrognosisABSTRACT
Endometritis constitutes a major problem in the management of broodmares; hence, diagnostic tests with a high sensitivity and specificity are highly appreciated. The aim of this study was to compare the results from endometrial, cytologic, and bacteriologic examinations obtained by a newly developed, double-guarded, flushing technique versus standard diagnostic tests, the double-guarded swab and biopsy. The described double-guarded flush technique requires the use of a disposable uterine flushing tube, a sanitary sleeve, a sterile steel speculum, and a 250 mL fluid bag. Endometrial biopsies, swabs, and low-volume lavage samples were obtained from 34 research mares at six different time points in four estrous cycles and were evaluated cytologically and bacteriologically. Endometrial biopsies from the first cycle (n = 34) were examined for the presence of polymorphonuclear neutrophils (PMNs) in the stratum compactum and stratum spongiosum and used as a gold standard for calculation of diagnostic sensitivity and specificity. In all samples, Escherichia coli was most frequently isolated (lavage, 30%; swab, 21%; and biopsy, 12%) followed by ß-hemolytic streptococci (lavage, 11%; swab, 8%; and biopsy, 7%). Positive cytology was less likely to occur when E coli was isolated from the diagnostic tests compared with the growth of ß-hemolytic streptococci. Isolation of pathogens from uterine samples was highly associated with the presence of PMNs in the stratum compactum and straum spongiosum on histology. Using the presence of PMNs in the tissue specimens as the gold standard for diagnosing endometritis, the sensitivity of low-volume lavage culture was 0.75 and the specificity was 0.72. In conclusion, the double-guarded, low-volume, lavage technique was a rapid and accurate method for diagnosing mares with endometritis, and the risk of false-positive samples is considered to be minimal compared with other flushing techniques described.
Subject(s)
Endometritis/veterinary , Horse Diseases/diagnosis , Horses , Therapeutic Irrigation/veterinary , Uterus , Animals , Biopsy/veterinary , Endometritis/diagnosis , Endometritis/microbiology , Endometrium/microbiology , Endometrium/pathology , Escherichia coli/isolation & purification , Female , Neutrophils/pathology , Sensitivity and Specificity , Therapeutic Irrigation/methodsABSTRACT
Some colon cancer (CC) patients present synchronous cancers at diagnosis and others develop metachronous neoplasms, but the risk factors are unclear for non-hereditary CC. We showed previously that global DNA demethylation increased with aging and correlated with genomic damage in CC, and we show now that preferentially associates to CCs with wild-type p53. This study aimed to elucidate the extent of DNA hypomethylation in patients with single and multiple CC, its relationship with aging, and its potential as predictive tool. We compared by real-time methylation-specific PCR the relative demethylation level (RDL) of long interspersed nucleotide element-1 (LINE-1) sequences in matched cancer tissues and non-cancerous colonic mucosa (NCM) from patients with single and multiple right-sided CCs. Although no RDL difference was found in NCM from single CC patients and healthy volunteers (P=0.5), there was more demethylation (higher RDL) in NCM from synchronous cancer patients (P=1.1 × 10(-5)) multiple CCs also were more demethylated than single CCs (P=0.0014). High NCM demethylation was predictive for metachronous neoplasms (P=0.003). In multivariate logistic regression analyses RDL was the only independent predictor for metachronous (P=0.02) and multiple (P=4.9 × 10(-5)) tumors. The higher LINE-1 demethylation in NCM from patients with multiple (synchronous and metachronous) tumors (P=9.6 × 10(-7)) was also very significant in patients with tumors without (P=3.8 × 10(-6)), but not with (P=0.16) microsatellite instability. NCM demethylation increased with aging in patients with single tumors, but decreased in those with multiple tumors. Moreover, the demethylation difference between patients with single vs multiple tumors appeared higher in younger (P=3.6 × 10(-4)) than in older (P=0.0016) patients. These results predict that LINE-1 hypomethylation in NCM can be used as an epigenetic predictive biomarker for multiple CC risk. The stronger association of demethylation in NCM with multiple CC risk from younger patients also suggests an inherited predisposition for the apparent field cancerization effect of somatic demethylation.
Subject(s)
Colon/metabolism , DNA Methylation , Genetic Predisposition to Disease , Neoplasms/genetics , Aged , Female , Humans , Long Interspersed Nucleotide Elements , Male , Middle Aged , Polymerase Chain ReactionABSTRACT
A double tracer technique was used successfully to quantify whole-site methane (CH(4)) emissions from Fakse Landfill. Emissions from different sections of the landfill were quantified by using two different tracers. A scaled-down version of the tracer technique measuring close-by to localized sources having limited areal extent was also used to quantify emissions from on-site sources at the landfill facility, including a composting area and a sewage sludge storage pit. Three field campaigns were performed. At all three field campaigns an overall leak search showed that the CH(4) emissions from the old landfill section were localized to the leachate collection wells and slope areas. The average CH(4) emissions from the old landfill section were quantified to be 32.6 ± 7.4 kg CH(4)h(-1), whereas the source at the new section was quantified to be 10.3 ± 5.3 kg CH(4)h(-1). The CH(4) emission from the compost area was 0.5 ± 0.25 kg CH(4)h(-1), whereas the carbon dioxide (CO(2)) and nitrous oxide (N(2)O) flux was quantified to be in the order of 332 ± 166 kg CO(2)h(-1) and 0.06 ± 0.03 kg N(2)Oh(-1), respectively. The sludge pit located west of the compost material was quantified to have an emission of 2.4 ± 0.63 kg h(-1) CH(4), and 0.03 ± 0.01 kg h(-1) N(2)O.
Subject(s)
Air Pollutants/analysis , Environmental Monitoring/methods , Methane/analysis , Refuse Disposal/statistics & numerical data , Air Pollutants/metabolism , Air Pollution/statistics & numerical data , Methane/metabolism , Nitrogen Dioxide/analysis , Nitrogen Dioxide/metabolism , Spectroscopy, Fourier Transform InfraredABSTRACT
A laser photoacoustic spectroscopy (LPAS) instrument was developed and used for aircraft measurements of ethene from industrial sources near Houston, Texas. The instrument provided 20 s measurements with a detection limit of less than 0.7 ppbv. Data from this instrument and from the GC-FID analysis of air samples collected in flight agreed within 15% on average. Ethene fluxes from the Mt. Belvieu chemical complex to the northeast of Houston were quantified during 10 different flights. The average flux was 520 +/- 140 kg h(-1) in agreement with independent results from solar occultation flux (SOF) measurements, and roughly an order of magnitude higher than regulatory emission inventories indicate. This study shows that ethene emissions are routinely at levels that qualify as emission upsets, which need to be reported to regional air quality managers.
Subject(s)
Air Pollutants/analysis , Ethylenes/analysis , Spectrum Analysis/methods , AcousticsABSTRACT
In this prospective randomized multicenter trial 93 patients, median age 72 years, with RAEB-t (n=25) and myelodysplastic syndrome (MDS)-AML (n=68) were allocated to a standard induction chemotherapy regimen (TAD 2+7) with or without addition of granulocyte-macrophage-CSF (GM-CSF). The overall complete remission (CR) rate was 43% with no difference between the arms. Median survival times for all patients, CR patients, and non-CR patients were 280, 550, and 100 days, respectively, with no difference between the arms. Response rates were significantly better in patients with serum lactate dehydrogenase (S-LDH) levels =9.5 microkat/l, bone marrow cellularity =70%, and WBC counts <4.0 x 10(9)/l, but S-LDH was the only variable independently associated with response by logistic regression analysis. Cox's regression analysis identified four significant prognostic factors for survival: bone marrow cellularity, S-LDH, cytogenetic risk group (International Prognostic Scoring System), and age. Only bone marrow cellularity (P=0.01) and S-LDH (P=0.0003) retained statistical significance in the log-rank test. Severe adverse events were significantly more common in the GM-TAD arm (P=0.01). Thus, addition of GM-CSF to chemotherapy showed no clinical benefit in terms of response but carried an increased risk for side effects. We present a clinically useful tool to predict response to chemotherapy and survival in elderly patients with transforming MDS, favoring patients with features of less proliferative disease.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Cytarabine/therapeutic use , Daunorubicin/therapeutic use , Granulocyte-Macrophage Colony-Stimulating Factor/therapeutic use , Leukemia, Myeloid/drug therapy , Thioguanine/therapeutic use , Acute Disease , Adult , Aged , Aged, 80 and over , Anemia, Refractory, with Excess of Blasts/drug therapy , Anemia, Refractory, with Excess of Blasts/pathology , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Cell Transformation, Neoplastic , Cytarabine/adverse effects , Daunorubicin/adverse effects , Female , Follow-Up Studies , Granulocyte-Macrophage Colony-Stimulating Factor/administration & dosage , Humans , Leukemia, Myeloid/pathology , Male , Middle Aged , Myelodysplastic Syndromes/drug therapy , Myelodysplastic Syndromes/pathology , Prospective Studies , Remission Induction , Survival Rate , Thioguanine/adverse effectsABSTRACT
Quantitative analysis of assemblage similarity among chitinozoan and acritarch associations recovered from various sedimentary sequences across the Trans European Suture Zone (TESZ; southern Baltic Sea and northern Germany region), permits evaluation of changes in microplankton palaeobiogeography during the Ordovician in the study area. The present data confirm strong palaeobiogeographic differences between the lower Ordovician of the Rügen area, and the coeval domains of the East European Platform (EEP), corroborating the idea that the subsurface of Rügen should be considered palaeogeographically as the eastern extension of Avalonia.Cluster analysis of chitinozoan assemblages from numerous wells in the Rügen area, and one well from the southern margin of the EEP indicates that chitinozoan bioprovincialism reached its maximum during the Llanvirn; during this period, the Rügen microplankton communities were clearly Gondwanan in character. Calculations using the coefficient of similarity support the conclusion of a high similarity between Llanvirn acritarch assemblages from the Rügen subsurface and from coeval Perigondwana localities (e.g. Tunisia). Since the early Caradoc, this Gondwanan affinity of the Rügen microfossils starts to lessen, and becomes negligible during the late Caradoc. During latest Caradoc-early Ashgill through Llandovery times the chitinozoan assemblages from either side of the TESZ are undistinguishable. If palaeobiogeographical differentiation is primarily related to palaeolatitudinal distance, then the present data support closure of the Tornquist Ocean during late Caradoc-Ashgill times. The presence of reworked Llanvirn acritarchs of Perigondwanan affinity in middle Ashgill sedimentary sequences at the southern margin of the EEP, clearly shows that by this time erosion of an uplifted area was taking place. Accordingly, the closure of the Tornquist Ocean, and consequent Avalonia-Baltica collision must have taken place during the time interval between the middle Caradoc and the early middle Ashgill (Rawtheyan).New chitinozoan data from boreholes H 2 and K 5, offshore of Rügen Island, northern Germany, allow for precise biostratigraphic dating. In the pre-Devonian part of H 2, Siphonochitina formosa indicates an Abereiddian (Early Llanvirn) age, facilitating correlation with boreholes Binz 1/73 and Lohme 2/70 of Rügen. In borehole K 5, the occurrence of Belonechitina robusta and Tanuchitina bergstroemi permits attribution of the investigated pre-Carboniferous sequence to the middle-late Caradoc, and, possibly, early Ashgill.
ABSTRACT
Methane is an important climate gas contributing significantly to global warming. A large part of the anthropogenic emissions of methane comes from landfills. Due to the biogenic origin of these emissions and the inhomogeneous characteristics of landfills and their soil cover, these emissions show large spatial variation. Thus, development of reliable and cost-effective methods for measurements of these emissions is an important task and a challenge to the scientific community. Traditionally, field chamber methods have been used but also different area integrating methods based on downwind plume measurements. These measurements have been supported by meteorological data either directly from local measurements or by controlled release of tracer gas from the landfill providing the dispersion characteristics of the plume. In this paperwe describe a method,the Time Correlation Tracer method, combining controlled tracer gas release from the landfill with time-resolved concentration measurements downwind the landfill using FTIR absorption spectroscopy. The method has been tested and used on measurements at a landfill in southern Sweden over the past 1.5 years. The method has proven to be a usable method for measurements of total methane emission from landfills, and under favorable meteorological conditions we estimate an achievable accuracy of 15-30%. The real time analysis capability of the FTIR makes it possible to judge the success of the measurement already on site and to decide whether more measurements are necessary. The measurement strategy is relatively simple and straightforward, and one person can make a measurement from a medium sized landfill (1-4 ha) within a few days to a week depending on the meteorological situation.
Subject(s)
Air Pollutants/analysis , Methane/analysis , Spectroscopy, Fourier Transform Infrared/methods , Nitrous Oxide/analysis , Soil , SwedenABSTRACT
We have previously demonstrated that platelets in polycythaemia vera (PV) exhibit decreased aggregation after stimulation with platelet activating factor (PAF) and reduced expression of GPIIIa on both resting and stimulated platelets. In the present study, we investigated if these results were related to changes in the mobilization of intracellular calcium, activation of phospholipase D (PLD) or amounts of GPIIIa and the intracellular tyrosine kinases Fak, Syk, Grb2, Shc and rhoA. Intracellular calcium levels were not different in resting platelets from 14 PV patients and 15 healthy controls (median 43 nmol/L, range 10-114, vs. 36 nmol/L, range 10-119). After stimulation with PAF (1 micromol/L) an equal increase was seen (125 nmol/L for PV platelets, range 67-257, vs. 113 nmol/L for controls, range 60-250). Also formation of phosphatidyl ethanol (PEt) was similar after exposure to 0.5 U/ml thrombin (0.28% PEt of total phospholipid, range 0.16-1.10, vs. 0.24 for controls, range 0.11-2.3) and 1 micromol/L PMA (0.25, range 0.16-0.32, vs. 0.14, range 0.09-0.6). In contrast to the reduced amount of GPIIIa on the surface of PV platelets, immunoblotting on whole cell lysates showed no reduction in PV patients compared to controls, indicating the possibility of an impaired incorporation of GPIIIa to the cell membrane. Levels of Fak, Syk, Shc, Grb2 and rhoA appeared equal in patients and controls. Similar intracellular proteins were tyrosine phosphorylated after stimulation with thrombin, PAF and PMA. In summary, defective platelet aggregation after stimulation with PAF is caused by neither defective mobilization of intracellular calcium nor, in contrast to the situation in PV granulocytes, an impaired activation of PLD. Moreover, no apparent differences in the intracellular amounts of Fak, Syk Shc, Grb2 and rhoA could be detected between PV and control platelets.
Subject(s)
Adaptor Proteins, Signal Transducing , Calcium Signaling/physiology , Focal Adhesions/metabolism , Phospholipase D/pharmacology , Platelet Aggregation/drug effects , Polycythemia Vera/blood , Aged , Aged, 80 and over , Antigens, CD/pharmacology , Calcium/metabolism , Enzyme Precursors/metabolism , Enzyme Precursors/pharmacology , Female , Focal Adhesion Kinase 1 , Focal Adhesion Protein-Tyrosine Kinases , Focal Adhesions/chemistry , GRB2 Adaptor Protein , Humans , Integrin beta3 , Integrins/blood , Intracellular Signaling Peptides and Proteins , Intramolecular Transferases/metabolism , Intramolecular Transferases/pharmacology , Kinetics , Male , Middle Aged , Phosphatidylethanolamines/metabolism , Phospholipase D/blood , Phospholipase D/metabolism , Phosphorylation/drug effects , Platelet Activating Factor/pharmacology , Platelet Membrane Glycoproteins/pharmacology , Polycythemia Vera/physiopathology , Protein-Tyrosine Kinases/metabolism , Protein-Tyrosine Kinases/pharmacology , Proteins/metabolism , Proteins/pharmacology , Syk Kinase , Tyrosine/metabolism , rhoA GTP-Binding Protein/metabolism , rhoA GTP-Binding Protein/pharmacologyABSTRACT
Polycythaemia vera (PV) is a myeloproliferative disorder (MPD) characterized by an increased production of mature blood cells. The underlying pathogenic mechanisms behind PV are largely unknown. Thrombopoietin (TPO) is the most important cytokine for stimulation of megakaryocyte growth and formation of functional platelets. Recently, it has been shown that the receptor for TPO, c-mpl, is expressed on haematopoietic stem cells, and that TPO promotes the growth of these stem cells via binding to c-mpl. Quantitative or qualitative abnormalities of c-mpl function could thus theoretically play a role in the pathogenesis of different MPDs. Previous studies of the integrity of the c-mpl system in PV have produced conflicting results. We therefore studied c-mpl protein expression using immunoblot analysis in 15 PV patients and 10 healthy controls. Seven out of 15 PV patients (47%) exhibited similar c-mpl protein levels to the controls, whereas eight out of 15 patients (53%) showed either markedly reduced or absent levels of c-mpl. Five of the seven c-mpl-positive patients had only been treated by phlebotomy, whereas six out of eight c-mpl-negative patients were receiving treatment with hydroxyurea, anagrelide or alpha-interferon. Disease duration tended to be slightly longer in c-mpl-negative patients compared with c-mpl-positive patients (mean = 55 vs. 43 months). Tyrosine phosphorylation of JAK-2 in immunoprecipitates of platelets obtained after stimulation with TPO (100 and 1000 ng/ml) was normal in c-mpl-positive patients, whereas it could not be detected in c-mpl-negative patients. We therefore conclude that there exists a marked heterogeneity in c-mpl protein levels and functional integrity in PV. However, it seems less likely that c-mpl abnormalities per se are directly involved in the pathogenesis leading to the occurrence of PV, as c-mpl levels were similar to those seen in healthy individuals in about half of the patients under study.
Subject(s)
Blood Platelets/metabolism , Neoplasm Proteins , Polycythemia Vera/blood , Proto-Oncogene Proteins/metabolism , Receptors, Cytokine , Aged , Aged, 80 and over , Female , Humans , Immunoblotting , Janus Kinase 2 , Male , Middle Aged , Polycythemia Vera/etiology , Protein-Tyrosine Kinases/metabolism , Receptors, ThrombopoietinABSTRACT
Chitinozoans from seven Ordovician units (Abbaye de Villers, Tribotte, Rigenée, Ittre, Bornival, and Brutia formations and a new unnamed unit, here provisionally called the Asquempont unit) belonging to the mainly concealed Brabant Massif, Belgium are described herein. Fifty-six samples were taken from rocks cropping out at the south-eastern rim of the massif in the Orneau, Dyle-Thyle and Senne-Sennette valleys. Microfossil preservation is moderate to poor, and the chitinozoans occur in low numbers. Taxonomically, the recovered chitinozoans are distributed into 29 taxa, some placed under open nomenclature. Together with earlier published graptolite and acritarch data, the analysis of the chitinozoan assemblages resulted in an improved chronostratigraphy of the investigated formations. We propose a local chitinozoan biozonation with 11 zones for the Brabant Massif. The oldest investigated units yielded chitinozoans typical for North Gondwana, and younger units (starting in the middle Caradoc), yielded some taxa also common in Baltica. As the Brabant Massif formed part of the microcontinent Avalonia, the chitinozoan assemblages recovered from the massif support the inferred drifting of Avalonia from high latitudes towards middle latitudes in the Ordovician as was suggested earlier.
ABSTRACT
The island of Rügen (NE Germany), situated close to the Trans-European Suture Zone (TESZ), in the southern Baltic Sea is underlain by sedimentary rocks of an Early Palaeozoic age, known only from boreholes. The wells, Rügen 5/66 and Binz 1/73, were investigated for their chitinozoan assemblages to improve the earlier biostratigraphic dating (graptolites and acritarchs) and to facilitate comparisons with other chitinozoan assemblages on both sides of the TESZ. In the lower part of the Rügen 5/66 core (3794.7-3615.8m), Lagenochitina destombesi Elaouad-Debbaj is indicative of an early late Tremadoc age. In the upper part of the same well (3287.3-1709.7m), the observed chitinozoan taxa suggest an age spanning the early Llanvirn to the Caradoc. The entire sampled interval of the Binz 1/73 core (5217.6-5041.8m) is interpreted as belonging to the Siphonochitina formosa Biozone (early-early late Abereiddian, corresponding to the early Llanvirn). The chitinozoan data corroborate the earlier suggested biostratigraphic ages, based on acritarchs and graptolites. The chitinozoans from the Binz 1/73 well point to a high latitude provenance of the investigated host sediments at time of deposition.
ABSTRACT
OBJECTIVE: In clinical practice, patients with polycythaemia vera (PV) are monitored by measurement of venous packed cell volume (PCV). However, whereas treatment recommendations are still based upon studies in which the results were obtained with the centrifuged microhaematocrit, currently in most instances automated blood cell counters are used to calculate PCV. In a group of patients with polycythaemia we therefore compared the results obtained by the microhaematocrit method with PCV calculated by haematology analysers. DESIGN: The study was carried out on a prospective basis. Duplicate venous blood samples were collected. The centrifuged microhaemotocrit was obtained by using an IEC Micro-MB Centrifuge. Depending on different routine methods used in the participating hospitals, the blood cell counter PCV was calculated using Coulter STKS, Bayer Technicon H2 or H3. SETTING: Patients were included from four Swedish university hospitals: Akademiska (Uppsala), Huddinge and Karolinska (Stockholm) and Sahlgrenska (Göteborg). SUBJECTS: Seventy-four patients with PV and 10 patients with secondary polycythaemia were included and a total of 150 duplicate blood samples were analysed from these subjects. RESULTS: In the 150 measurements the mean blood cell counter calculated PCV was 0.448 +/- 0.037; the mean for centrifuged microhaematocrit was 0.467 +/- 0. 037 and the difference between means was highly significant (P = 6.8 x 10-25). The means for centrifuged haematocrit and calculated PCV differed significantly in the groups of PV patients treated with phlebotomy only, hydroxyurea or radiophosphorous (P < 0.0001, respectively). In PV patients treated with alpha-interferon and in patients with secondary polycythaemia the difference in means did not reach statistical significance (P = 0.07 and P = 0.13, respectively). The groups of patients with MCV <80 fL and >/=80 fL both presented significant differences between means for calculated PCV and centrifuged haematocrit. CONCLUSIONS: If PV patients are monitored with blood cell counter calculated PCV it appears that the therapeutic goal should be to maintain the calculated PCV below 0.43, provided the local differences in calculated PCV and centrifuged haematocrit are of the same magnitude as in this study.
Subject(s)
Hematocrit , Polycythemia Vera/blood , Aged , Aged, 80 and over , Female , Hematocrit/methods , Humans , Male , Middle Aged , VeinsABSTRACT
A 35-year-old female presented with isolated thrombocytopenia of autoimmune origin. One and a half years later, hypoplastic myelodysplastic (MDS) was diagnosed. Following treatment with cyclosporin A, erythropoietin and granulocyte colony-stimulating factor, the patient has achieved a sustained hematological remission which is still ongoing after 3 years. Furthermore, to the best of our knowledge, this is the third case described in the literature where treatment with cytokines alone or in combination with immunosuppressive agents has resulted in a long standing cytogenetic response in MDS.
Subject(s)
Cyclosporine/therapeutic use , Erythropoietin/therapeutic use , Granulocyte Colony-Stimulating Factor/therapeutic use , Myelodysplastic Syndromes/drug therapy , Adult , Autoimmune Diseases/drug therapy , Autoimmune Diseases/pathology , Disease Progression , Drug Therapy, Combination , Female , Humans , Myelodysplastic Syndromes/pathology , Platelet Count/drug effects , Remission Induction/methods , Thrombocytopenia/drug therapy , Thrombocytopenia/pathologyABSTRACT
Autologous peripheral blood stem cell transplantation (APSCT) is increasingly used in the treatment of breast cancer. We report a patient who experienced septic shock, and after treatment with antibiotics, high-dose corticosteroids and mechanical ventilation due to respiratory insufficiency, developed quadriplegia. Electroneurophysiological examination, as well as a muscle biopsy, showed a typical picture of acute quadriplegic myopathy with loss of thick filament proteins. This is, to the best of our knowledge, the first reported case of this complication following APSCT.
Subject(s)
Breast Neoplasms/therapy , Hematopoietic Stem Cell Transplantation/adverse effects , Quadriplegia/etiology , Acute Disease , Female , Humans , Middle Aged , Transplantation, AutologousABSTRACT
We have previously described a stimulus-specific defect in platelet aggregation in polycythaemia vera (PV) after stimulation with surface receptor dependent agonists such as platelet activating factor (PAF). In contrast, responses to phorbol myristate acetate (PMA) were normal. We now report that after PAF stimulation, using flow cytometry, the amount of fibrinogen bound to its receptor was significantly lower in PV platelets with a median MFI of 6.0 (range 4.1-17.3) compared to controls, 12.8 (range 8-21.3; n=11; p<0.01). We found no evidence of preactivation of PV platelets. Quantitative analysis of GPIIIa gave a significantly lower number of GPIIIa on resting PV platelets, 14300 subunits of GPIIIa (range 8500-15500) vs. 19800 for controls (range 13400-26800; n=12; p<0.01). Both patients and controls increased their number of receptors on the cell surface after stimulation with PAF and PMA, but the significant difference in the number of receptors per cell remained. Indirect evaluation of PAF receptor function showed that activation of CD 62 did not differ in PV and controls after PAF stimulation. Additionally, although the basal level of serotonin in platelet-rich plasma was significantly lower in PV, there was a threefold increase of the basal level after stimulation with PAF for both PV and control platelets, also indicating a normal interaction of PAF with its receptor. Although our results indicate both an impaired PAF induced aggregation in PV and a lower number of GPIIb/IIIa complexes on single platelets, whether these phenomena are related remains uncertain.
Subject(s)
Blood Platelets/metabolism , Fibrinogen/metabolism , Platelet Glycoprotein GPIIb-IIIa Complex/metabolism , Polycythemia Vera/blood , Adult , Aged , Aged, 80 and over , Antigens, CD/blood , Blood Platelets/drug effects , Female , Flow Cytometry , Humans , Male , Middle Aged , Platelet Activating Factor/pharmacology , Platelet Activation/drug effects , Platelet Glycoprotein GPIIb-IIIa Complex/analysis , Serotonin/blood , Tetradecanoylphorbol Acetate/pharmacologyABSTRACT
Treatment with erythropoietin (epo) may improve the anemia of myelodysplastic syndromes (MDS) in approximately 20% of patients. Previous studies have suggested that treatment with the combination of granulocyte colony-stimulating factor (G-CSF) and epo may increase this response rate. In the present phase II study, patients with MDS and anemia were randomized to treatment with G-CSF + epo according to one of two alternatives; arm A starting with G-CSF for 4 weeks followed by the combination for 12 weeks, and arm B starting with epo for 8 weeks followed by the combination for 10 weeks. Fifty evaluable patients (10 refractory anemia [RA], 13 refractory anemia with ring sideroblasts [RARS], and 27 refractory anemia with excess blasts [RAEB]) were included in the study, three were evaluable only for epo as monotherapy and 47 for the combined treatment. The overall response rate to G-CSF + epo was 38%, which is identical to that in our previous study. The response rates for patients with RA, RARS, and RAEB were 20%, 46%, and 37%, respectively. Response rates were identical in the two treatment groups indicating that an initial treatment with G-CSF was not neccessary for a response to the combination. Nine patients in arm B showed a response to the combined treatment, but only three of these responded to epo alone. This suggests a synergistic effect in vivo by G-CSF + epo. A long-term follow-up was made on 71 evaluable patients from both the present and the preceding Scandinavian study on G-CSF + epo. Median survival was 26 months, and the overall risk of leukemic transformation during a median follow-up of 43 months was 28%. Twenty patients entered long-term maintenance treatment and showed a median duration of response of 24 months. The international prognostic scoring system (IPSS) was effective to predict survival, leukemic transformation, and to a lesser extent, duration of response, but had no impact on primary response rates.
Subject(s)
Anemia/drug therapy , Anemia/physiopathology , Erythropoietin/administration & dosage , Granulocyte Colony-Stimulating Factor/administration & dosage , Myelodysplastic Syndromes/physiopathology , Aged , Aged, 80 and over , Drug Therapy, Combination , Female , Follow-Up Studies , Humans , Male , Middle Aged , Treatment OutcomeABSTRACT
Modern treatment has dramatically improved the prognosis for patients with polycythaemia vera (PV). Here a patient is described who has been followed and treated for PV for over 30 years, demonstrating that very long term survival can be achieved in PV. However, effective treatment modalities such as radioactive phosphorus, alkylating agents and, most recently, hydroxyurea, have all been shown to increase the risk to develop acute leukaemia when used in the treatment of myeloproliferative disorders. Hopefully, the prolonged survival of this patient may help to emphasize the need to use non-leukaemogenic agents when treating younger PV patients.