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Background PBSC collected following G-CSF priming lead to more rapid hemopoietic reconstitution (HR) after autologous transplantation than do unprimed BMstem cells. However, PBSC have a number of disadvantages compared with BM cells, including the need for an extended collection period and requirement for good venous access. Methods We retrospectively analysed our experience with an alternative source of hemopoietic stem cells, G-CSF primed BM. Fortyfour patients who underwent BM harvesting after 6 days' administration of G-CSF, at a dose of 5 μg/kg per day, were compared with an equal number who underwent standard (unprimed) BM harvesting. We also analysed HR after autologous transplantation in 16 patients who received unprimed BM, 18 who received G-CSF-primed BM and 14 who received PBSC. Results G-CSF-primed BM was collected more quickly (p<0.00005) and yielded a larger number of cells (p<0.0001) than unprimed BM. Consequently, larger numbers of cells were available for administration following transplantation with G-CSF-primed BM. The results of HR after transplantation with G-CSF primed BM were intermediate between those of unprimed BM and PBSC. For example, platelet independence (unsupported platelet count ≥ 20 × 10 9 /L) occurred after 22 days with unprimed BM, 14 days with G-CSF-printed BM and 10 days with PBSC (p for trend <0.0001) and the mean number of days when platelet transfusions were given was 10, 6 and 3 respectively (p for trend <0.005). These results reflected transplant cell doses. Conclusion G-CSF-primed BM is a valuable source of hemopoietic stem cells for autologous transplantation and a useful alternative to PBSC to certain circumstances. [ABSTRACT FROM AUTHOR]

Agricultural soils are a major source of the potent greenhouse gas and ozone depleting substance, N 2 O. To implement management practices that minimize microbial N 2 O production and maximize its consumption (i.e., complete denitrification), we must understand the interplay between simultaneously occurring biological and physical processes, especially how this changes with soil depth. Meaningfully disentangling of these processes is challenging and typical N 2 O flux measurement techniques provide little insight into subsurface mechanisms. In addition, denitrification studies are often conducted on sieved soil in altered O 2 environments which relate poorly to in situ field conditions. Here, we developed a novel incubation system with headspaces both above and below the soil cores and field-relevant O 2 concentrations to better represent in situ conditions. We incubated intact sandy clay loam textured agricultural topsoil (0-10 cm) and subsoil (50-60 cm) cores for 3-4 days at 50% and 70% water-filled pore space, respectively. 15 N-N 2 O pool dilution and an SF 6 tracer were injected below the cores to determine the relative diffusivity and the net N 2 O emission and gross N 2 O emission and consumption fluxes. The relationship between calculated fluxes from the below and above soil core headspaces confirmed that the system performed well. Relative diffusivity did not vary with depth, likely due to the preservation of preferential flow pathways in the intact cores. Gross N 2 O emission and uptake also did not differ with depth but were higher in the drier cores, contrary to expectation. We speculate this was due to aerobic denitrification being the primary N 2 O consuming process and simultaneously occurring denitrification and nitrification both producing N 2 O in the drier cores. We provide further evidence of substantial N 2 O consumption in drier soil but without net negative N 2 O emissions. The results from this study are important for the future application of the 15 N-N 2 O pool dilution method and N budgeting and modelling, as required for improving management to minimize N 2 O losses., (© 2023 The Authors. European Journal of Soil Science published by John Wiley & Sons Ltd on behalf of British Society of Soil Science.)

In grazing systems, urine patches deposited by livestock are hotspots of nutrient cycling and the most important source of nitrous oxide (N 2 O) emissions. Studies of the effects of urine deposition, including, for example, the determination of country-specific N 2 O emission factors, require natural urine for use in experiments and face challenges obtaining urine of the same composition, but of differing concentrations. Yet, few studies have explored the importance of storage conditions and processing of ruminant urine for use in subsequent gaseous emission experiments. We conducted three experiments with sheep urine to determine optimal storage conditions and whether partial freeze-drying could be used to concentrate the urine, while maintaining the constituent profile and the subsequent urine-derived gaseous emission response once applied to soil. We concluded that filtering of urine prior to storage, and storage at - 20 °C best maintains the nitrogen-containing constituent profile of sheep urine samples. In addition, based on the 14 urine chemical components determined in this study, partial lyophilisation of sheep urine to a concentrate represents a suitable approach to maintain the constituent profile at a higher overall concentration and does not alter sheep urine-derived soil gaseous emissions.

Urine patches deposited in pasture by grazing animals are sites of reactive nitrogen (N) loss to the environment due to high concentrations of N exceeding pasture uptake requirements. In order to upscale N losses from the urine patch, several urination parameters are required, including where, when and how often urination events occur as well as the volume and chemical composition. There are limited data available in this respect, especially for sheep. Here, we seek to address this knowledge gap by using non-invasive sensor-based technology (accelerometers) on ewes grazing in situ, using a Boolean algorithm to detect urination events in the accelerometer signal. We conducted an initial study with penned Welsh Mountain ewes (n = 5), with accelerometers attached to the hind, to derive urine flow rate and to determine whether urine volume could be estimated from ewe squat time. Then accelerometers attached to the hind of Welsh Mountain ewes (n = 30 at each site) were used to investigate the frequency of sheep urination events (n = 35 946) whilst grazing two extensively managed upland pastures (semi-improved and unimproved) across two seasons (spring and autumn) at each site (35-40 days each). Sheep urinated at a frequency of 10.2 ± 0.2 and 8.1 ± 0.3 times per day in the spring and autumn, respectively, while grazing the semi-improved pasture. Urination frequency was greater (19.0 ± 0.4 and 15.3 ± 0.3 times per day in the spring and autumn, respectively) in the unimproved pasture. Ewe squat duration could be reliably used to predict the volume of urine deposited per event and was thus used to estimate mean daily urine production volumes. Sheep urinated at a rate of 16.6 mL/s and, across the entire dataset, sheep squatted for an average of 9.62 ± 0.03 s per squatting event, producing an estimated average individual urine event volume of 159 ± 1 mL (n = 35 946 events), ranging between 17 and 745 mL (for squat durations of 1 to 45 s). The estimated mean daily urine volume was 2.15 ± 0.04 L (n = 2 669 days) across the entire dataset. The data will be useful for modelling studies estimating N losses (e.g. ammonia (NH 3 ) volatilisation, nitrous oxide (N 2 O) emission via nitrification and denitrification and nitrate (NO 3 - ) leaching) from urine patches., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

Nitrous oxide (N 2 O) is an air pollutant of major environmental concern, with agriculture representing 60% of anthropogenic global N 2 O emissions. Much of the N 2 O emissions from livestock production systems result from transformation of N deposited to soil within animal excreta. There exists a substantial body of literature on urine patch N 2 O dynamics, we aimed to identify key controlling factors influencing N 2 O emissions and to aid understanding of knowledge gaps to improve GHG reporting and prioritize future research. We conducted an extensive literature review and random effect meta-analysis (using REML) of results to identify key relationships between multiple potential independent factors and global N 2 O emissions factors (EFs) from urine patches. Mean air temperature, soil pH and ruminant animal species (sheep or cow) were significant factors influencing the EFs reviewed. However, several factors that are known to influence N 2 O emissions, such as animal diet and urine composition, could not be considered due to the lack of reported data. The review highlighted a widespread tendency for inadequate metadata and uncertainty reporting in the published studies, as well as the limited geographical extent of investigations, which are more often conducted in temperate regions thus far. Therefore, here we give recommendations for factors that are likely to affect the EFs and should be included in all future studies, these include the following: soil pH and texture; experimental set-up; direct measurement of soil moisture and temperature during the study period; amount and composition of urine applied; animal type and diet; N 2 O emissions with a measure of uncertainty; data from a control with zero-N application and meteorological data., (© 2020 The Authors. Global Change Biology published by John Wiley & Sons Ltd.)

Extensively grazed grasslands are understudied in terms of their contribution to greenhouse gas (GHG) emissions from livestock production. Mountains, moorlands and heath occupy 18% of the UK land area, however, in situ studies providing high frequency N 2 O emissions from sheep urine deposited to such areas are lacking. Organic soils typical of these regions may provide substrates for denitrification-related N 2 O emissions, however, acidic and anoxic conditions may inhibit nitrification (and associated emissions from nitrification and denitrification). We hypothesised urine N 2 O-N emission factors (EFs) would be lower than the UK country-specific and IPCC default value for urine, which is based on lowland measurements. Using automated GHG sampling chambers, N 2 O emissions were determined from real sheep urine (930 kg N ha -1 ) and artificial urine (920 kg N ha -1 ) applied in summer, and from an artificial urine treatment (1120 kg N ha -1 ) and a combined NO 3 - and glucose treatment (106 kg N ha -1 ; 213 kg C ha -1 ) in autumn. The latter treatment provided an assessment of the soils capacity for denitrification under non-substrate limiting conditions. The artificial urine-N 2 O EF was 0.01 ± 0.00% of the N applied in summer and 0.00 ± 0.00% of the N applied in autumn. The N 2 O EF for real sheep urine applied in summer was 0.01 ± 0.02%. A higher flux was observed in only one replicate of the real urine treatment, relating to one chamber where an increase in soil solution NO 3 - was observed. No lag phase in N 2 O emission was evident following application of the NO 3 - and glucose treatment, which emitted 0.69 ± 0.15% of the N applied. This indicates nitrification rates are the bottle-neck for N 2 O emissions in upland organic soils. We calculated the potential impact of using hill-grazing specific urine N 2 O EFs on the UK inventory of N 2 O emissions from sheep excreta, and found a reduction of ca. 43% in comparison to the use of a country-specific excretal EF., (Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Data regarding ethical issues encountered by medical students during the surgical clerkship are sparse. Identification of such issues facilitates development of an ethics curriculum that ensures student preparation for issues most frequently encountered on the surgical rotation. To better understand these issues, we performed content analysis of reflections written by medical students about ethical issues encountered during their surgical clerkship., Materials and Methods: All medical students on the surgical clerkship at a university hospital from 4/2017 to 6/2018 submitted a written reflection regarding an ethical issue encountered during the clerkship. Two investigators performed content analysis of each reflection. References to ethical principles (beneficence, nonmaleficence, justice, autonomy) were tabulated. Ethical issues were classified into main categories and subcategories, based on a modified version of a previously published taxonomy., Results: 134 reflections underwent content analysis. Nonmaleficence was the most frequently mentioned ethical principle. 411 specific ethical issues were identified. Ethical issues were distributed across ten main categories: decision-making (28%), communication among health care team members (14%), justice (12%), communication between providers, patients, and families (9%), issues in the operating room (9%), informed consent (9%), professionalism (5%), supervision/student-specific issues (5%), documentation (1%), and miscellaneous/other (8%). We identified two ethical issues infrequently discussed in previous reports: delivery of efficient yet high-quality care and poor communication between services/consultants., Conclusions: Students encounter diverse ethical issues during their surgical clerkships. Ethical and contextual considerations related to these issues should be incorporated into a preclinical/clinical surgical ethics curriculum to prepare students to understand and engage the challenges they face during the clerkship., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Nitrification inhibitors (NIs) such as dicyandiamide (DCD) and 3,4-dimethylpyrazole phosphate (DMPP) provide an opportunity to reduce losses of reactive nitrogen (Nr) from agricultural ecosystems. To understand the fate and efficacy of these two inhibitors, laboratory-scale experiments were conducted with 14 C-labelled DCD and DMPP to determine the relative rates of mineralization, recovery in soil extracts and sorption in two agricultural soils with contrasting pH and organic matter content. Concurrently, the net production of soil ammonium and nitrate in soil were determined. Two months after NI addition to soil, significantly greater mineralization of 14 C-DMPP (15.3%) was observed, relative to that of 14 C-DCD (10.7%), and the mineralization of both NIs increased with temperature, regardless of NI and soil type. However, the mineralization of NIs did not appear to have a major influence on their inhibitory effect (as shown by the low mineralization rates and the divergent average half-lives for mineralization and nitrification, which were 454 and 37days, respectively). The nitrification inhibition efficacy of DMPP was more dependent on soil type than that of DCD, although the efficacy of both inhibitors was lower in the more alkaline, low-organic matter soil. Although a greater proportion of DMPP becomes unavailable, possibly due to physico-chemical sorption to soil or microbial immobilization, our results demonstrate the potential of DMPP to achieve higher inhibition rates than DCD in grassland soils. Greater consideration of the interactions between NI type, soil and temperature is required to provide robust and cost-effective advice to farmers on NI use., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Telomere length has a biological link to cancer, with excessive telomere shortening leading to genetic instability and resultant malignant transformation. Telomere length is heritable and genetic variants determining telomere length have been identified. Telomere biology has been implicated in the development of hematological malignancies (HMs), therefore, closer examination of telomere length in HMs may provide further insight into genetic etiology of disease development and support for telomere length as a prognostic factor in HMs. We retrospectively examined mean relative telomere length in the Tasmanian Familial Hematological Malignancies Study using a quantitative PCR method on genomic DNA from peripheral blood samples. Fifty-five familial HM cases, 191 unaffected relatives of familial HM cases and 75 non-familial HM cases were compared with 758 population controls. Variance components modeling was employed to identify factors influencing variation in telomere length. Overall, HM cases had shorter mean relative telomere length (p=2.9×10-6) and this was observed across both familial and non-familial HM cases (p=2.2x10-4 and 2.2x10-5, respectively) as well as additional subgroupings of HM cases according to broad subtypes. Mean relative telomere length was also significantly heritable (62.6%; p=4.7x10-5) in the HM families in the present study. We present new evidence of significantly shorter mean relative telomere length in both familial and non-familial HM cases from the same population adding further support to the potential use of telomere length as a prognostic factor in HMs. Whether telomere shortening is the cause of or the result of HMs is yet to be determined, but as telomere length was found to be highly heritable in our HM families this suggests that genetics driving the variation in telomere length is related to HM disease risk.

The high degree to which plant roots compete with soil microbes for organic forms of nitrogen (N) is becoming increasingly apparent. This has culminated in the finding that plants may consume soil microbes as a source of N, but the functional significance of this process remains unknown. We used (15) N- and (14) C-labelled cultures of soil bacteria to measure rates of acquisition of microbes by sterile wheat roots and plants growing in soil. We compared these rates with acquisition of (15) N delivered as nitrate, amino acid monomer (l-alanine) and short peptide (l-tetraalanine), and the rate of decomposition of [(14) C] microbes by indigenous soil microbiota. Acquisition of microbe (15) N by both sterile roots and roots growing in soil was one to two orders of magnitude slower than acquisition of all other forms of (15) N. Decomposition of microbes was fast enough to account for all (15) N recovered, but approximately equal recovery of microbe (14) C suggests that microbes entered roots intact. Uptake of soil microbes by wheat (Triticum aestivum) roots appears to take place in soil. If wheat is typical, the importance of this process to terrestrial N cycling is probably minor in comparison with fluxes of other forms of soil inorganic and organic N., (© 2013 The Authors. New Phytologist © 2013 New Phytologist Trust.)

We describe a collection of 11 families with ≥ 2 generations of family members whose condition has been diagnosed as a hematologic malignancy. In 9 of these families there was a significant decrease in age at diagnosis in each subsequent generation (anticipation). The mean age at diagnosis in the first generation was 67.8 years, 57.1 years in the second, and 41.8 years in the third (P < .0002). This was confirmed in both direct parent-offspring pairs with a mean reduction of 19 years in the age at diagnosis (P = .0087) and when the analysis was repeated only including cases of mature B-cell neoplasm (P = .0007). We believe that these families provide further insight into the nature of the underlying genetic mechanism of predisposition in these families.

A family history of a haematological malignancy (HM) is known to be a risk factor for HMs. However, collections of large families with multiple cases of varied disease types are relatively rare. We describe a collection of 12 families with dense aggregations of multiple HM subtypes. Cases were ascertained from a population based study conducted between 1972 and 1980 in Tasmania, Australia. Diagnoses were confirmed through review and re-examination of stored tissue, pathology reports, Tasmanian Cancer Registry and flow cytometry records. Family trees were generated and kinship coefficients were calculated for all pairs of affected individuals. 120 cases were found in these families. Cases diagnosed with chronic lymphocytic leukaemia (CLL) demonstrated the most significantly increased aggregation (P < 0.0001). There was also significant evidence that those individuals diagnosed at an older age (>53 years), did not aggregate together in families with disease that presented at an earlier age (<20 years) (P = 0.009).

Aim: To evaluate the accuracy of the CoaguChek XS international normalised ratio (INR) monitor compared with the laboratory method., Methods: The accuracy and ease of use of the recently marketed CoaguChek XS portable INR monitor was evaluated in 17 patients involved in a trial of warfarin home monitoring. INR results from the monitor were compared with those from the laboratory method. Clinical applicability was measured by discrepant INR values, defined in the literature by expanded and narrow agreement criteria, and by the proportion of INR values differing by >15% and by >20% from those derived by the laboratory method., Results: Participants provided 59 comparison INR measurements for analysis. The paired results were highly correlated (r = 0.91). Expanded and narrow agreement between paired INR values occurred 100% of the time. Only three CoaguChek XS (5.1%) results differed by >15% compared with the laboratory method; no results differed by >20% or were discrepant by >0.5 INR units., Conclusions: In the hands of patients the CoaguChek XS showed good correlation with laboratory determination of INR and compared well with expanded and narrow clinical agreement criteria. Both patients and doctors were highly satisfied with the accuracy and ease of use of the CoaguChek XS.

Objective: To compare the accuracy and clinical usefulness of the near-patient testing CoaguChek S INR monitor in rural medical practice. DESIGN, SETTING AND MAIN OUTCOME MEASURES: General practices were identified through Australian university departments of rural health. Study investigators trained general practitioners and/or practice nurses in the use of the CoaguChek S INR monitor. General practices obtained a fingerprick sample for testing with the INR monitor to compare with conventional pathology testing for accuracy. An evaluation questionnaire was administered to users of the machine to assess ease of use and clinical usefulness., Results: A total of 169 patients from 15 general practice sites provided 401 paired (CoaguChek S and laboratory) INR results. The CoaguChek S was found to be accurate when compared to laboratory INR (r = 0.89), despite complicating variables such as multiple users of the monitor and multiple laboratories used for comparison with the CoaguChek S INR. Overall, 88% of dual INR measurements were within 0.5 INR units of each other. For laboratory INR /= 3.6, 97%, 90% and 57% of readings were within 0.5 INR units, respectively. Clinical agreement occurred 93% and 90% of the time against published expanded and narrow criteria, respectively., Conclusions: The routine use of near-patient testing, with appropriate training and quality assurance programs, has the potential to increase the safety and efficacy of warfarin therapy in rural and remote communities.

The accuracy and reproducibility of the CoaguChek S, and its clinical agreement with conventional laboratory international normalized ratio (INR) determination, were evaluated in an outpatient anticoagulation clinic setting. Forty-three patients provided 248 paired INR measurements for analysis. The paired results were highly correlated (r = 0.90). The mean coefficient of variation for the CoaguChek S for a random sample of 21 patients with three repeated tests each, was 4%. Clinical applicability was also measured by discrepant INR values, as defined in the literature by expanded and narrow agreement, and by INR values resulting in a different clinical decision by a blinded haematology registrar. Expanded agreement and narrow agreement between the two INR values occurred 90 and 88% of the time, respectively. The stricter criteria set down by the clinician resulted in 73% of paired results producing the same dosage decision. The CoaguChek S displayed good correlation with laboratory determination of INR and compared relatively well with expanded and narrow clinical agreement criteria.

Harvesting of stem cells during the early phases of treatment with no immediate intention to perform a stem cell transplant is becoming an increasingly common practice. Such "insurance" harvests are often stored for many years before being needed for transplant in a subsequent relapse. The effect of long-term cryostorage (5-14 years) on the viability and functional capacity of haematopoietic stem cells (HSCs) was investigated in 40 bone marrow and peripheral blood harvests using standard in vitro methods, the colony forming unit-granulocyte/macrophage (CFU-GM) assay and a single platform viable CD34(+) cell absolute count by flow cytometry. Forty percent of harvests had CD34(+) HSC counts of at least 0.7 x 10(6)/kg bodyweight and 85% had CFU-GM counts of at least 1.0 x 10(5)/kg bodyweight, these values representing our institutional minimum requirements for safe transplantation. Based on these results, it appears that HSC collections can remain adequate for safe transplantation after up to 14 years of cryostorage. However, as deterioration of HSC quality and viability may occur, some precautions may be warranted, namely harvesting higher than normal numbers of HSCs in collections intended for long-term storage and repeating in vitro assays on harvests after long-term storage prior to transplantation.

Pathologic splenic rupture in non-Hodgkin's lymphoma (NHL) is a rare event, with 32 cases previously reported. Initial presentation of NHL with this complication is even rarer. We report such a case in an 80-year-old man with mantle cell lymphoma (MCL). It is notable that of the previously reported cases of pathologic rupture, three have occurred in MCL, suggesting that patients with this uncommon subtype of NHL may be particularly vulnerable to pathologic splenic rupture. Following splenectomy the patient's disease behaved in a high-grade fashion. Despite an initially encouraging response, his disease ran an aggressive course and he succumbed within four months. This case demonstrates the presentation of MCL with pathologic splenic rupture, as well as the potentially highly malignant behaviour of the disease.

The effects on bone marrow cellularity and morphology of 6 days' treatment with granulocyte colony-stimulating factor (G-CSF) in 35 patients were studied. Examination of trephine biopsies showed a highly significant increase in cellularity (P < 10-13). Assessment of aspirates revealed an increase in the myeloid to erythroid (M : E) ratio (P = 0.00006), the proportion of myeloid cells (P < 10-8), myelocytes (P = 0.00007), metamyelocytes (P = 0.04), band forms (P = 0.0005) and neutrophils (P = 0.02). This study presents a comprehensive analysis of the effects of six days' administration of G-CSF on human bone marrow.

The myelodysplastic syndromes (MDS) are a group of clonal disorders, common especially in the elderly, characterised by cytopenias and dysfunctional blood cells. They are a cause of significant morbidity and premature mortality. The cause is not known in most cases. Predisposing factors that have been identified include cytotoxic chemotherapy, benzene and other environmental mutagens, and bone marrow transplantation. Clinically patients present with effects of deficiency of erythrocytes, neutrophils and/or platelets or the diagnosis may be made unexpectedly after routine blood testing. The bone marrow is generally hypercellular and often disorganized; abnormal in vitro cell growth is common. Non-random cytogenetic abnormalities are characteristic and helpful diagnostically; certain subtypes are associated with specific clinical and cytological features. Especially noteworthy are the 5q- and 7-syndromes. The outlook generally is poor. Death comes about from transformation to acute myeloid leukemia (AML), from the complications of cytopenias, or from intercurrent illness. Treatment is unsatisfactory except in young patients who can undergo allografting. Treatments of uncertain value include intensive or gentle chemotherapy. Of the cytokines erythropoietin and granulocyte-macrophage colony-stimulating factor (GM-CSF) so far seem the most promising. However, for the majority management is limited to provision of appropriate supportive care.

At transformation of refractory anemia with ring sideroblasts to acute nonlymphocytic leukemia (ANLL) the bone marrow cells of a 75-year-old woman showed three different karyotypes, i.e., 46,XX,46,XX,t(1;3)(p36;q21) and 46,XX,t(1;3)(p36;q21),t(14;17)(q32;q21). She received no antileukemic therapy, and 1 year later, all her bone marrow cells were t(1;3)(p36;q21),t(14;17)(q32;q21). In association with the onset and first 11 months of ANLL, the platelet count increased 10-fold to a peak of 750 x 10(9)/L, providing further evidence that the t(1;3)(p36;q21) translocation causes stimulation of thrombopoiesis. Six months after transformation, her red cells showed reduced expression of A and Leb antigens. Serum alpha-n-3-acetylgalactosaminyl transferase (blood group A transferase) and red cell adenylate kinase were both reduced. The genes for both these substances are at 9q34, which suggests an abnormality here, although cytogenetically chromosome 9 appeared normal. This is the first case with t(1;3)(p36;q21) to show concurrent loss of red cell antigens and the first report detailing the course of untreated ANLL with t(1;3)(p36;q21).

As part of an epidemiological survey of myelodysplastic syndromes (MDS) in southern Tasmania, 62 MDS patients identified over a 2 year period were tested for the presence of CD34, the human progenitor cell antigen (HPCA), in their peripheral blood. The results were correlated with transformation to acute myeloid leukemia (AML) and patient survival, and CD34+ status was compared as a prognostic indicator with Bournemouth score, cytogenetics, and CFU-GM colony growth which were also assessed. Circulating CD34+ cells were found in 23 of the 62 MDS patients; 9 of the 23 patients with circulating CD34+ cells transformed to AML, as compared with none of the 39 CD34 negative patients (P less than 0.0001); and 11 of the 23 patients with circulating CD34+ cells were dead at the end of the 2 year period, as opposed to 6 of the 39 with no CD34+ cells (P less than 0.03). The Bournemouth score was also significantly associated with transformation to AML (P less than 0.0001) and poor survival (P less than 0.04). These were the only significant associations of the possible prognostic factors studied with either transformation or survival. In summary, the presence of circulating CD34+ cells was significantly associated with both progression to AML and poor survival and was found to be a better prognostic indicator than cytogenetics or CFU-GM colony growth.

Infusion of prostaglandin D2 (PGD2) into dogs for 60 minutes at a rate of 1 microgram/kg/min produced a marked and rapid reduction in circulating eosinophils within 2 minutes, without any significant change in neutrophil count. Recovery was also rapid, with levels similar to those of a control group of dogs being reached 60 minutes after finishing the infusion. In dogs given PGD2 the hematocrit rose more rapidly than in the control group. The platelet count did not alter significantly.

Daunorubicin, thioguanine and cytosine arabinoside were administered from the 17th to 34th weeks of pregnancy in a 23-year-old patient with acute myeloid leukaemia. The patient went into remission of her leukaemia, and a normal male infant was born after labour was induced in the 40th week. This experience supports the view that modern regimens of anti-leukaemic drugs may be administered during the second and third trimesters of pregnancy without harmful effects on the foetus.

A 43-year-old man with lifelong anaemia showed features which indicate him to have a previously undescribed variant of congenital dyserythropoietic anaemia (CDA), type II. The main clinical features--of which the first two are unique or very unusual in CDA--have been severe tophaceous gout, massive splenomegaly, gall stones mecessitating cholecystectomy and haemosiderosis affecting the liver and probably the heart. At age 41 he sustained a spontaneous retinal detachment. In the peripheral blood there were large numbers of nucleated red blood cells and marked macrocytosis; otherwise the picture was typical of CDA type II. The bone marrow contained many bi- and multi-nucleated erythrocyte precursors. There were increased levels of a number of red cell enzymes and a slightly raised level of HbF. Uncharacteristically, the red cells failed to lyse with acidified normal serum. The cells were strongly agglutinated by anti-i and were of the rare Kpb-negative phenotype. Plasma lipid analysis showed very low levels of cholesterol and vitamin E. Lipid peroxidation was markedly increased. Ultrastructural studies showed reduplication of the erythrocyte, granulocyte, and platelet cell membranes.

This canine study was designed to evaluate the effects of the intravenous infusion of coliform endotoxin with a simultaneous infusion of prostaglandin D2 (PGD2) on hemodynamics, blood gas, blood chemistry, and some hematologic parameters. The information derived from the present study supports the view that the intravenous administration of PGD2 moderates the effects of endotoxin, with its main beneficial effect being on the renal vascular bed. Treatment with PGD2 did not change the endotoxin-induced hemoconcentration, or the reduction in the platelet and white blood cell counts. However, four of nine animals survived more than 7 days when treated with PGD2, whereas without it only one of nine animals survived the administration of the same dose of endotoxin. Although the mechanism of action is not clear, the correlation between PGD2 infusion and improved renal blood flow warrants further study in endotoxic shock.

To determine whether a simple immunoperoxidase (IP) technique could replace the traditional immunofluorescence (IF) technique (by fluorescence microscopy) for determination of phenotype and monoclonality in cell suspensions from patients with lymphoproliferative disorders, we tested samples from 48 cases by both methods, using small panels of antibodies designed to determine proportions of B-cells, T-cells and cells bearing immunoglobulin light chains. There were 27 cases of chronic lymphocytic leukaemia (CLL), 6 of prolymphocytic leukaemia (ProLL), and 15 of non-Hodgkin's lymphoma (NHL). We found that IP was at least as reliable as IF in all cases. In the 47 B-cell cases, the mean proportion of cells apparently belonging to the malignant clone was higher by IP than by IF; conversely, the proportion of B-cells displaying the non-malignant light chain marker and the proportion of residual T-cells was apparently lower by IP. We conclude that IP is a useful and reliable technique for determining phenotype and monoclonality in lymphoproliferative disorders; because it is tolerant of delays to samples in transit and requires only simple facilities, it may be particularly suitable for small laboratories.

In southern Tasmania, Australia, primary Epstein-Barr virus infection occurs in adults greater than 30 years of age at a higher frequency (approximately 13% of all cases) than is generally reported for other parts of the world, and approximately 7% of the general population of the region have no antibodies to the virus. Epstein-Barr virus should not be overlooked as a possible cause of disease in older patients in similar populations elsewhere.

Dose-response effects of prostaglandin D2 (0.125, 0.25, 0.5, and 0.75 micrograms/kg/min) infused intravenously in pentobarbital-anesthetized dogs were studied with particular reference to renal, pulmonary, and systemic effects. Another group receiving the vehicle alone served as controls. Prostaglandin D2 administration resulted in a significant dose-dependent increase in renal artery flow, urine output, creatinine clearance, plasma renin activity, sodium excretion, potassium excretion, and pulmonary artery pressure. A significant decrease occurred in renal resistance and arterial PO2. There were no appreciable changes in mean arterial pressure, heart rate, hematocrit, platelet count, arterial pH, and PCO2. In the vehicle control group, all other parameters remained relatively stable, except for some increase in the mean arterial pressure, plasma renin activity, and potassium excretion. The results of this study suggest that prostaglandin D2 administered intravenously at levels lower than those required to produce adverse pulmonary and systemic effects will improve the renal blood flow and function.

This paper describes a modification of the peroxidase technique by which immunophenotyping may be carried out on routinely air-dried blood and bone marrow (BM) smears. The method is simple and quick, requires no special equipment, can be performed on fresh or stored specimens and gives a standard of morphological detail equal to that of routine blood films. With a monoclonal anti-HLA-DR antibody as a prototype, it was possible to demonstrate reliably, the presence of positively and negatively stained cells of appropriate morphological types in the peripheral blood of leukemia patients. Although only about one-third of antibodies tested were effective with the technique, we identified monoclonal antibodies capable of demonstrating myelomonocyte, granulocyte, monocyte, pan-leukocyte, transferrin, platelet, pan-T, 'cALLA plus B cell' and other antigens. However, we have not yet found antibodies able to identify T cell subsets, nor to distinguish 'common' acute lymphoblastic leukemia from its rare B-cell counterpart. With these limitations the method is suitable for routine use alongside cytochemistry in the differential diagnosis of leukemias and lymphomas.