Quantifying the frequency and volume of urine deposition by grazing sheep using tri-axial accelerometers.

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 (NH3) volatilisation, nitrous oxide (N2O) emission via nitrification and denitrification and nitrate (NO3-) leaching) from urine patches.

Accuracy, reproducibility and clinical utility of the CoaguChek S portable international normalized ratio monitor in an outpatient anticoagulation clinic.

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.

Association between high interleukin-6 levels and adverse outcome after autologous haemopoietic stem cell transplantation.

We studied interleukin-6 (IL-6) levels on the day of transplantation in 31 patients undergoing autologous haemopoietic stem cell transplantation (SCT) (either peripheral blood stem cell transplantation (PBSCT) or bone marrow transplantation (BMT)) for neoplastic diseases to determine if there was a relationship between IL-6 level and rate of haemopoietic recovery, length of stay in hospital, and survival. There was no apparent delay in post-transplant recovery associated with elevated IL-6 levels. However, increased values of IL-6 tended to be associated with an increased length of stay in hospital (P = 0.083). There was a highly significant adverse association between higher IL-6 levels and survival following transplantation (P = 0.0001). This association remained significant (P = 0.013) in the uniform subgroup of patients with malignant lymphoma with chemosensitive disease who had undergone BMT (that is, excluding patients who had undergone PBSCT) (n = 13). Knowledge of IL-6 levels on the day of transplant has the potential to provide valuable prognostic information in patients undergoing autologous haemopoietic SCT.

Pathologic splenic rupture as the presentation of mantle cell lymphoma.

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 effect of G-CSF on the composition of human bone marrow.

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.

Hemopoietic stem-cell harvesting and transplantation using G-CSF-primed BM: comparison with unprimed BM and G-CSF-primed PBSC.

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 microg/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 > or = 20 2 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.

Myelodysplastic syndromes.

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.

Acute leukemia with t(1;3)(p36;q21), evolution to t(1;3)(p36;q21), t(14;17)(q32;q21), and loss of red cell A and Le(b) antigens.

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).

Circulating CD34+ cells: an adverse prognostic factor in the myelodysplastic syndromes.

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.

Seroepidemiological study of infectious mononucleosis in older patients.

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-dependent effects of prostaglandin D2 on hemodynamics, renal function, and blood gas analyses.

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.

Comparison of immunofluorescence and immunoperoxidase techniques for demonstration of phenotype and monoclonality in lymphoproliferative disorders.

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.

A rapid, simple method for leukemia immunophenotyping using air-dried blood and bone marrow smears.

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.

The effect of prostaglandin D2 (PGD2) on circulating eosinophils.

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.

Prostaglandin D2 in canine endotoxic shock. Hemodynamic, hematologic, biochemical, and blood gas analyses.

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.

Congenital dyserythropoietic anaemia (CDA) with severe gout, rare Kell phenotype and erythrocyte, granulocyte and platelet membrane reduplication: a new variant of CDA type II.

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.

Normal infant after treatment of acute myeloid leukaemia in pregnancy with daunorubicin.

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.