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Biomedical subjects

I Walker

Publications and source records attributed to I Walker.

At least 55 records · Page 3Linked to original sources

The use of anti-D to improve post-transfusion platelet response: a randomized trial.

Patients undergoing induction chemotherapy for acute leukaemia often become refractory to platelet transfusions. Increased clearance of transfused platelets due to alloimmune destruction has been identified as one of the primary mechanisms contributing to this refractory state. We performed a double-blind randomized trial to determine whether the administration of anti-D to Rh-positive individuals could prevent the refractory state and improve post-transfusion platelet response. Rh-positive patients with acute leukaemia undergoing induction chemotherapy and requiring platelet transfusions were allocated to weekly intravenous anti-D (20 micrograms/kg) or placebo. Platelets and red cell concentrates were administered according to standardized transfusion guidelines. Outcome measures included platelet transfusion utilization, red cell utilization, platelet recovery 18-24 h post-infusion, and the percentage of patients refractory to platelet transfusion. There were 43 patients studied: 21 received anti-D and 22 saline placebo. The mean number of platelet concentrates required per day of observation was 0.59 (SD 0.22) in the anti-D group and 0.61 (SD 0.22) in the placebo group, P = 0.86. No difference was detected between groups in terms of platelet recovery post-infusion, refractoriness to platelet transfusion or frequency of infection (P = 0.97). Red cell concentrate utilization was significantly increased in the anti-D group compared to the placebo group, 0.58 units per day versus 0.37 units per day respectively, P = 0.005. We conclude that the use of anti-D did not improve post-transfusion platelet response in Rh positive patients with acute leukaemia, but did result in an increased need for red cell transfusion.

Acute Disease↗

Randomized trial of interferon maintenance in multiple myeloma: a study of the National Cancer Institute of Canada Clinical Trials Group.

PURPOSE: To determine whether interferon maintenance therapy improves overall survival and response duration in patients with multiple myeloma who have responded to induction therapy with melphalan and prednisone. PATIENTS AND METHODS: In a multicenter trial, patients with symptomatic clinical stage I and stage II and III multiple myeloma were registered at diagnosis and those who responded to melphalan-prednisone (MP) were randomized either to receive interferon (2 mU/m2) subcutaneously three times per week or no maintenance. MP was discontinued in both groups once a stable response plateau of the monoclonal protein was reached. Interferon was continued until relapse, and then was restarted on subsequent response to MP. Interferon toxicity was recorded using a self-report diary. Survival and response duration were calculated using life-table methods, and were adjusted in the analysis for imbalances in baseline prognostic factors. RESULTS: Four hundred two patients were registered and 176 responders were randomized (85 to interferon and 91 to control). At a median follow-up time of 43 months, the median survival duration was 43 months for interferon and 35 months for control (P = .16), but when adjusted for chance imbalances in baseline prognostic factors (mainly performance status), the median survival duration was 44 months and 33 months for interferon and control, respectively (P = .049). Progression-free survival from randomization to first relapse also favored interferon (unadjusted P < .002; adjusted P < .003). Interferon toxicity caused 58% of patients to reduce their dose, of which 84% were able to return to the initial dose; 14% had to discontinue interferon treatment. CONCLUSION: Interferon maintenance therapy improves progression-free and overall survival of patients with multiple myeloma who respond to melphalan and prednisone. Toxicity is substantial and must be weighed by patients against the potential benefits in response duration and survival.

Aged↗

The role of the plasma from platelet concentrates in transfusion reactions.

BACKGROUND: Febrile, nonhemolytic transfusion reactions are the most frequent adverse reactions to platelets. A number of observations argue against the widely held view that these reactions result from the interaction between antileukocyte antibodies in the recipient and leukocytes in the platelet product. We sought to determine whether substances in the plasma or the cells in the product cause reactions to transfused platelets. METHODS: We separated standard platelet concentrates into their plasma and cellular components and then transfused both portions in random order. Patients were monitored for reactions during all transfusions. Before each transfusion, the concentration of cytokines (interleukin-1 beta and interleukin-6) was measured in the platelet products. Studies were also performed on the platelet products to determine the effect of storage on the concentration of cytokines. RESULTS: Sixty-four pairs of platelet-product components (the plasma supernatant and the cells) were administered to 12 patients. There were 20 reactions to the plasma supernatant and 6 reactions to the cells (chi-square = 6.50, P = 0.009). Eight transfusions were associated with reactions to both products. The plasma component was more likely to cause severe reactions than the cells (chi-square = 9.6, P < 0.01). A strong positive correlation was observed between the reactions and the concentration of interleukin-1 beta and interleukin-6 in the plasma supernatant (P < 0.001 and P = 0.034, respectively). In vitro studies demonstrated that interleukin-1 beta and interleukin-6 concentrations rise progressively in stored platelets and that these concentrations are related to the leukocyte count in the platelet product. CONCLUSIONS: Bioreactive substances in the plasma supernatant of the platelet product cause most febrile reactions associated with platelet transfusions. Removing the plasma supernatant before transfusion can minimize or prevent these reactions.

Adult↗

Evaluation of two supplements for the prevention of alfalfa bloat.

Poloxalene and a mineral mixture feed supplement patented for the treatment of emphysema, polyarthritis, and other pectin related diseases were tested in two trials for their ability to prevent bloat in cattle fed fresh alfalfa. Each trial had a crossover design using three Jersey steers with rumen fistulas per group. Each trial period continued until the total number of cases of bloat reached > or = 24. Treatments were given at 0800 each day. The mineral mixture was given at 100 g/d and 190 mg/kg body weight per day in the first and second trials, respectively. Poloxalene, which was tested only in the second trial, was given at 23 mg/kg body weight per day. Each group of steers was then fed 200 kg of freshly harvested alfalfa in the vegetative to early bloom stages of growth at 0830. In the first trial, only 69% as many cases of bloat occurred on the mineral mixture as on the control treatment, but no significant difference was detected in the second trial. The potency of the alfalfa may have been higher in the second trial, when forage dry matter was lower, magnesium and soluble nitrogen were higher, and bloat occasionally occurred twice a day. Bloat did not occur when the steers were treated with poloxalene. In these trials, poloxalene was completely effective in preventing bloat, but the mineral mixture was only partially so.

Animal Feed↗

Warfarin-induced skin necrosis in 2 patients with protein S deficiency: successful reinstatement of warfarin therapy.

Warfarin-induced skin necrosis is a rare but serious complication of oral anticoagulant therapy. This condition has been associated with protein C deficiency but only rarely reported in patients with a deficiency of protein S. We have managed 2 patients with a history of warfarin-induced skin necrosis who were diagnosed as being protein-S-deficient. Since both patients were candidates for long-term anticoagulant therapy we elected to reintroduce warfarin using a regimen designed to minimize the risk of recurrent skin necrosis. While they were therapeutically anticoagulated with heparin, warfarin was started at 1 mg/day and the dose was increased gradually. Heparin was not discontinued until the prothrombin times were in the therapeutic range for at least 72 h. Both patients tolerated the reinstitution of warfarin without difficulty and they have now been followed for over 2 years on oral anticoagulants without complication.

Adult↗

Empathy, effectiveness and donations to charity: social psychology's contribution.

Charity organizations often use mailed requests to solicit donations from the public. This is not an efficient way to raise large amounts of money. The challenge addressed in this study was to use social psychology's knowledge of helping processes to make mailed requests more effective. Two constructs were identified as possibly useful: empathy and perceived effectiveness of helping. These were manipulated in a field experiment in a 2 x 2 x 2 factorial design (two levels of empathy, two of need extent, and two of need persistence--the last two factors operationalized perceived effectiveness). Letter soliciting donations to a well-known charity were mailed to a random sample of 2648 people in Perth, Western Australia. Manipulations of the three variables were embedded in the letters. The two effectiveness manipulations produced significant main effects, whereas the empathy manipulation was ineffective. We argue that social psychology's knowledge of helping processes is too confined to narrow, theoretical, laboratory-based phenomena to be directly and immediately applicable to the practices of charities.

Charities↗

The pattern of population growth as a function of redundancy and repair.

A basic model of hierarchical structure, expressed by simple, linear differential equations, shows that the pattern of population growth is essentially determined by conditions of redundancy in the sub-structure of individuals. There does not exist any possible combination between growth rate and accident rate that could balance population numbers and/or the level of redundancy within the population; all possible combinations either lead to extinction or to positive population growth with a decline of the fraction of individuals with redundant substructure. Declining populations, however, can be held fluctuating between certain limits by periodic phases of sub-unit repair. These results are particularly pertinent to the population dynamics of diploid (polyploid) organisms.

DNA Repair↗

Measurement of the transfer of the nitrogen moiety of intestinal lumen glutamic acid in man after oral ingestion of l-[15N]glutamic acid.

1. The measurement of the intestinal metabolism of the nitrogen moiety of glutamic acid has been investigated by oral ingestion of l-[15N]glutamic acid and sampling of arterialized blood. 2. Measurements have been made in six normal adults weighing an average of 72.8 kg ingesting 100 mg of l-[15N]glutamic acid after an overnight fast. 3. Measurement of the enrichment of arterial glutamic acid, glutamine and alanine was by gas chromatography-mass spectrometry. Isotopic enrichment of the amino acids was followed for 150 min after the ingestion of the amino acid. 4. Arterialized venous blood amino acid concentrations, measured by h.p.l.c., demonstrated no significant changes during the course of the experiment. 5. From the observed appearance of label in arterialized glutamic acid, alanine and glutamine, little luminal glutamic acid reaches the extracellular pool. The majority of the administered nitrogen label appears in the arterial alanine and glutamine components.

Administration, Oral↗

High-dose cytosine arabinoside as the initial treatment of poor-risk patients with acute nonlymphocytic leukemia: a Leukemia Intergroup Study.

Sixty-seven patients with newly diagnosed acute nonlymphocytic leukemia (ANLL) who were considered to be poor candidates for treatment with cytosine arabinoside (ara-C)/anthracycline antibiotic therapy were treated with high-dose ara-C (HDara-C) remission induction therapy. Thirty-four of the 67 patients had a hematologic disorder before developing acute leukemia or had a history of exposure to marrow toxins, 23 patients were greater than 70 years old, and 10 patients had medical problems that were felt to be a contraindication to therapy with an anthracycline antibiotic. Forty-two percent of patients entered complete remission (CR), whereas 22% failed to enter remission because of persistent leukemia. Treatment was associated with substantial toxicity varying from nausea and vomiting to irreversible cerebellar toxicity. Thirty-four percent of patients died during therapy. Poor performance status, a low serum albumin, and a low platelet count were associated with death during remission induction therapy, whereas a high pretherapy leukemic cell mass and a large number of residual leukemic cells in the marrow after six days of therapy were associated with treatment failure due to persistent leukemia.

Acute Disease↗

High-dose cytosine arabinoside in the treatment of preleukemic disorders: a leukemia intergroup study.

Fifteen patients with myelodysplastic/myeloproliferative disorders were treated with high-dose cytosine arabinoside therapy. While severe toxicity was produced in every patient, only two of the 15 patients entered complete remission and two achieved partial remission status. The therapeutic responses were confined to patients who had severe myelofibrosis of apparently recent onset.

Adult↗

Treatment of patients with acute nonlymphocytic leukemia in relapse: a Leukemia Intergroup study.

Forty patients with acute nonlymphocytic leukemia (ANLL) in first relapse were treated at eight member institutions of the Leukemia Intergroup with a 10-day continuous intravenous infusion of cytosine arabinoside and an anthracycline antibiotic administered on days 1, 2, and 3. Twenty of the 40 patients achieved a complete response. Seven of the patients who did not enter remission were drug-resistant failures, while 13 patients failed to enter remission for reasons other than persistent leukemia. Pretreatment parameters such as age, presence of infection, platelet count, and liver function tests were important predictors of survival. The percent bone marrow cellularity, the percent circulating abnormal (leukemic) cells, and the height of the white blood cell count prior to treatment were helpful in distinguishing patients who would enter remission from those who would not enter remission because of persistent leukemia.

Adolescent↗

Complex-irreversibility and evolution.

Both, irreversibility and evolution, imply order in time. It is argued that the only possible concept of time is a 'system-specific time', and that order in time is convertible into order in space and vice-versa. While life-less, complex systems are irreversible because of their complexity and, hence, not repeatable, living systems are reproduced by irreversible copy-reproduction and by coding. This mode of reproduction results of necessity in an arrow of time of growth and increasing complexity with death as its antagonist, and in obligatory spatial asymmetry. This arrow of increasing organic complexity is simultaneous with, and independent of, the arrow of increasing entropy. - A generalized, organic hierarchy is proposed as the model to study higher evolution. This hierarchy reproduces itself by differential rates of reproduction of its subunits within and between the various hierarchical levels of organization. Phylogenetic change is brought about by a change in this hierarchy's specific phase pattern of growth. Continuous and discrete organization is defined, and it is shown that specific relations between continuous and discrete levels within the hierarchy result in accumulation of neutral alleles. This accumulation is due to complex-irreversibility and causes genetic stabilisation, i.e. heritability, of the species-specific morphology of organisms.

Animals↗

The physical dimensions and biological meaning of the coefficients in the Volterra competition equations and their consequences for the possibility of coexistence.

Exact definitions in physical and biological terms of the coefficients in Volterra's (1926, 1931) original competition equations are indispensable for the understanding of the system. In agreement with Volterra's own, but not quite sufficient specifications, it is tried in this paper to give more precise definitions of the parameters used by Volterra. This leads to some consequences; i.a. that there does not exist a "principle of competitive exclusion". In order to allow for competitive exclusion - or for stabilization - the Volterra equations need additional biophysical specifications and mathematical modifications. Some such modifications are proposed, for instance for aggressive interference as a function of population numbers.

Animals↗

The low specificity of postoperative perfusion lung scan defects.

Ventilation and perfusion lung scans were performed preoperatively and postoperatively in 169 patients and classified blindly according to preset criteria. Perfusion lung scan abnormalities were present in 25 (15%) of the preoperative scans and 42 (25%) of the postoperative scans; 16 (38%) of the 42 abnormal postoperative scans were identical to the preoperative scans. Perfusion defects indicating a "high probability" of pulmonary embolism (lobar or segmental defects) were present in 5 preoperative scans and 10 postoperative scans; the 10 postoperative scans were classified as showing "definite" (5), "possible" (1) or "no" (4) pulmonary embolism on the basis of the preoperative scan and the ventilation scan; none of the 10 patients had clinical evidence of pulmonary embolism. Venous thrombosis was present in 12 patients, including 4 of the patients whose lung scans showed definite pulmonary embolism. Thus, postoperative perfusion lung scan defects are potentially misleading even when large.

Adult↗