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Biomedical subjects

J Redman

Publications and source records attributed to J Redman.

At least 19 recordsLinked to original sources
PubMed2005

Use of activated recombinant coagulation factor VII in patients undergoing reconstruction surgery for traumatic fracture of pelvis or pelvis and acetabulum: a double-blind, randomized, placebo-controlled trial.

BACKGROUND: Activated recombinant coagulation factor VII (rFVIIa) effectively prevents and controls bleeding in patients with coagulopathy. Data show that rFVIIa may reduce blood loss and eliminate the need for transfusion in patients with normal haemostasis undergoing major surgery. We assessed the efficacy of rFVIIa in patients with normal haemostasis undergoing repair surgery of major traumatic fracture of the pelvis or the pelvis and acetabulum, who were expected to have a large volume of blood loss. METHODS: We performed a double-blind, randomized, placebo-controlled trial involving 48 patients undergoing major pelvic-acetabular surgery. Patients were randomized to receive an i.v. bolus injection of rFVIIa 90 microg kg(-1) or placebo as add-on therapy at the time of the first skin incision. All patients also received intraoperative salvaged red blood cells (RBC). RESULTS: There was no significant difference in the total volume of perioperative blood loss, the primary outcome variable, between the rFVIIa and placebo groups. In addition, there were no differences between the two groups in the total volume of blood components, including salvaged RBC transfused, number of patients requiring allogeneic blood components, total volume of fluids infused, total operating time, time taken after entry to the intensive care unit to reach normal body temperature and acid-base status, and time spent in hospital. No adverse events, in particular thromboembolic events, were reported in either group. CONCLUSIONS: In patients with normal haemostasis undergoing repair surgery of traumatic pelvic-acetabular fracture, the prophylactic use of rFVIIa does not decrease the volume of perioperative blood loss.

Acetabulum↗
PubMed2005

Glucose in bronchial aspirates increases the risk of respiratory MRSA in intubated patients.

BACKGROUND: The risk of nosocomial infection is increased in critically ill patients by stress hyperglycaemia. Glucose is not normally detectable in airway secretions but appears as blood glucose levels exceed 6.7-9.7 mmol/l. We hypothesise that the presence of glucose in airway secretions in these patients predisposes to respiratory infection. METHODS: An association between glucose in bronchial aspirates and nosocomial respiratory infection was examined in 98 critically ill patients. Patients were included if they were expected to require ventilation for more than 48 hours. Bronchial aspirates were analysed for glucose and sent twice weekly for microbiological analysis and whenever an infection was suspected. RESULTS: Glucose was detected in bronchial aspirates of 58 of the 98 patients. These patients were more likely to have pathogenic bacteria than patients without glucose detected in bronchial aspirates (relative risk 2.4 (95% CI 1.5 to 3.8)). Patients with glucose were much more likely to have methicillin resistant Staphylococcus aureus (MRSA) than those without glucose in bronchial aspirates (relative risk 2.1 (95% CI 1.2 to 3.8)). Patients who became colonised or infected with MRSA had more infiltrates on their chest radiograph (p<0.001), an increased C reactive protein level (p<0.05), and a longer stay in the intensive care unit (p<0.01). Length of stay did not determine which patients acquired MRSA. CONCLUSION: The results imply a relationship between the presence of glucose in the airway and a risk of colonisation or infection with pathogenic bacteria including MRSA.

Adult↗
PubMed2001

Antiarrhythmic and haemodynamic effects of the commonly used intravenous electrolytes.

OBJECTIVE: To review the physiology and cardiovascular effects of the commonly used intravenous electrolytes. DATA SOURCES: Abstracts, articles and published reviews of studies reported from 1966 to 2000 and identified through a MEDLINE search on cardiac arrhythmias and electrolytes. SUMMARY OF REVIEW: While isotonic saline solutions are used to improve the haemodynamic status in critically ill patients who are hypotensive and hypovolaemic, other intravenous solutions including potassium chloride, calcium chloride, magnesium sulphate and sodium or potassium phosphate as well as hypertonic saline and sodium bicabonate have unique and often therapeutically useful haemodynamic and antiarrhythmic effects. Potassium chloride solutions are used to treat hypokalaemia with a maximum speed of correction in an adult of 20 mmol per 30 minutes when an acute myocardial infarct is present. A greater infusion rate may be necessary when ventricular or supraventricular tachyarrhythmias are present although close ECG monitoring will be required. Magnesium sulphate (2-20 mmol) has been used for hypomagnesaemic and normomagnesaemic cardiac arrhythmias (particularly when digoxin induced) and calcium chloride (3.4-6.8 mmol) is used to treat hyperkalaemic and hypermagnesaemic cardiac arrhythmias. Both hypertonic sodium bicarbonate and sodium chloride solutions have antiarrhythmic effects that may be beneficial in conditions that include tricyclic poisoning, hyperkalaemia and bupivicaine toxicity, although sodium bicarbonate is generally used for tricyclic cardiotoxicity. Low cardiac output states and arrhythmias have also been reported in hypophosphataemic patients that are reversed by infusions of potassium or sodium phosphate. CONCLUSIONS: Intravenous potassium chloride, calcium chloride, magnesium sulphate, sodium and potassium phosphate, sodium bicarbonate and hypertonic saline can be used effectively to alter the haemodynamic status and manage cardiac arrhythmias. However, their indications are selective and complications may occur, so careful administration and monitoring are required with their use.

Journal Article↗
PubMed2000

A xenobiotic-stress-activated transcription factor and its cognate target genes are preferentially expressed in root tip meristems.

In plants, as-1-type cis elements and their trans-acting factors confer tissue-specific and signal-responsive activities to the promoters of several glutathione S-transferase (GST) genes. Regulation of as-1 is widely thought to involve trans-acting factors that belong to a family of basic/leucine-zipper 'TGA factors' that selectively bind this element. We have previously shown that TGA 1a, a highly conserved TGA factor of tobacco, enhances transcription through as-1 in response to xenobiotic-stress cues. To better understand the functional contribution of this transcription factor to the expression of as-1-regulated genes, we have studied its tissue- and cell-specific localization in tobacco seedlings. We show here that the relative amount of TGA1a transcripts expressed in roots and shoots correlate with the as-1-regulated, basal-level expression of a GUS transgene and two putative target GST genes. In situ hybridization of intact seedlings demonstrated that TGA1a and these GST genes are preferentially expressed in root tip meristems. Similar findings were made with a gene-specific probe for PG13, a homologue of TGA1a, demonstrating that both factors are likely to be present in the same root meristem cells. Furthermore, TGA1a protein was immunologically detected exclusively in the primary root and its meristem. Collectively, these studies suggest that TGA1a, and perhaps PG13, may contribute to the expression of GST isoenzymes, especially in root tip meristems. The biological significance of these observations is discussed.

Basic-Leucine Zipper Transcription Factors↗
PubMed1999

An empirical test of language-relevant interventions for dementia.

The focus of this report is the treatment of persons with dementia who are of a non-English-speaking background (NESB). Noisemaking is one behavioral manifestation associated with severe dementia. It can have devastating effects on persons with dementia by limiting their access to activity programs and social interaction, and is also very distressing for professionals and family carers. It can be especially difficult for carers when they do not speak the first (non-English) language of the person with the noisemaking problem, when the person has lost his or her ability to speak English as the dementia progresses. Behavioral interventions have been found to be successful in decreasing the occurrence of noisemaking in some people with severe dementia. This article reports on a study of an elderly Italian woman with dementia. The study used a randomized, alternating-treatments design in order to determine whether an Italian-language intervention would be more effective in reducing her noisemaking than the same intervention given in English. The main result of the study was that the Italian intervention was found to be significantly more effective in reducing noisemaking than the English intervention. Therefore, this exploratory study provides empirical evidence for the increased effectiveness of an intervention program in the patient's original language. The study also demonstrates the need for individualized intervention programs, particularly for NESB patients living in predominantly English-speaking institutions.

Aged↗
PubMed1993

Serum interleukin 6 levels are elevated in lymphoma patients and correlate with survival in advanced Hodgkin's disease and with B symptoms.

Several cytokines including gamma-interferon, tumor necrosis factor alpha, interleukin 1 beta (IL-1 beta), and interleukin 6 (IL-6) are pyrogenic and can inhibit lipogenic processes. Because patients with lymphoma often suffer from fever, weight loss, and night sweats (B symptoms), the etiology of which is unknown, the authors investigated serum levels of these cytokines in normal volunteers and in patients with Hodgkin's and non-Hodgkin's lymphoma. Sixty serum samples from patients with Hodgkin's disease (28 patients) or non-Hodgkin's lymphoma (32 patients), as well as 20 samples from normal volunteers, were collected. The majority of patients had advanced (Stage III or IV) or relapsed disease. The assay for gamma-interferon was a specific and sensitive radioimmunoassay (lower limit of detection = 0.1 unit/ml); the assays for tumor necrosis factor alpha, IL-1 beta, and IL-6 were enzyme-linked immunoassays with lower limits of sensitivity of 10 pg/ml, 20 pg/ml, and 22 pg/ml, respectively. There were no statistically significant differences in gamma-interferon, tumor necrosis factor alpha, or IL-1 beta levels between lymphoma patients and normal subjects. In contrast, 20 of 57 patients (35%) with lymphoma as compared with 0 of 19 normal volunteers (0%) had detectable serum IL-6 levels (P < 0.005, chi 2 test). Interestingly, 17 of 29 lymphoma patients with B symptoms (59%) as opposed to 3 of 28 lymphoma patients without B symptoms (11%) had detectable serum IL-6 levels (P < 0.001, chi 2 test); the median IL-6 level was 28.9 pg/ml (B symptoms present) versus undetectable (no B symptoms) (P < 0.005, Mann-Whitney U test). Analyzing Hodgkin's and non-Hodgkin's lymphoma groups separately revealed similar results. IL-6 levels showed no significant correlation with time from diagnosis, beta 2-microglobulin, or lactate dehydrogenase levels. However, analysis by the method of Kaplan and Meir demonstrated that the median survival of Hodgkin's disease patients with detectable IL-6 levels (> or = 22 pg/ml) was 10 mo, whereas the median survival has not been reached at a median follow-up time of 37.5 mo in those patients with lower values (Wilcoxon P value = 0.0012). There were too few patients in each subset of non-Hodgkin's lymphoma to determine the correlation between IL-6 and survival but, considered as a single group, a statistically significant correlation was not found.(ABSTRACT TRUNCATED AT 400 WORDS)

Actuarial Analysis↗
PubMed1993

5-Oxo-eicosatetraenoate, a potent human neutrophil stimulus.

5-Oxo-eicosatetraenoate (5-oxoETE), a newly defined arachidonate metabolite, resembled 5-hydroxyeicosatetraenoate (5-HETE) in stimulating neutrophils to mobilize Ca2+ an in promoting PMN degranulation responses to other agents. It was, however, 10-fold stronger than 5-HETE and, like leukotriene (LT) B4, had intrinsic PMN degranulating effects. Nonetheless, 5-oxoETE and 5-HETE desensitized PMN to themselves or each other but not to LTB4; LTB4 desensitized to itself but not to 5-oxoETE or 5-HETE; and an antagonist blocked LTB4 but not 5-oxoETE or 5-HETE. 5-OxoETE and 5-HETE thus induce diverse PMN responses using a shared, down-regulatable, and receptor-like mechanism that does not involve LTB4 receptors; 5-oxoETE is the preferred natural agonist for this mechanism.

Arachidonic Acids↗
PubMed1991

Stage I-II low-grade lymphomas: a prospective trial of combination chemotherapy and radiotherapy.

Between 1984-1989, 44 patients with stage I-II low grade lymphoma were treated prospectively with sequential chemotherapy and involved-field radiotherapy. The chemotherapy was cyclophosphamide, vincristine, prednisone, and bleomycin (COP-Bleo); doxorubicin was included (CHOP-Bleo) for patients with adverse prognostic features (high LDH; extranodal sites; bulky nodes). Of the 44 patients, 37 had measurable disease and all have responded. With a median follow-up of 32 months, the 5-year survival and failure-free survival were 89% and 74%, respectively. Compared to past experience with involved-field radiotherapy alone, the failure-free survival is significantly better with COP-Bleo plus radiotherapy. The potentially cured fraction has risen from 40% to 74%.

Adult↗
PubMed1989

Receptor-independent metabolism of platelet-activating factor by myelogenous cells.

Human neutrophils incorporate and metabolize platelet-activating factor (PAF). We dissociated these events from PAF binding to its receptors. Cells were pretreated with either pronase, a PAF antagonist (L652731), or excess PAF. This reduced PAF receptor numbers by 70 to almost 100% but had no comparable effect upon the neutrophil's ability to metabolize PAF. Furthermore, HL-60 cells efficiently metabolized, but did not specifically bind, PAF. Thus, PAF receptor availability did not correlate with PAF metabolic capacity and we conclude that myelogenous tissues can process this bioactive ligand by a receptor-independent pathway.

Humans↗
PubMed1989

Fludarabine: a new agent with major activity against chronic lymphocytic leukemia.

Fludarabine was used to treat 68 patients with previously treated chronic lymphocytic leukemia (CLL). Nine (13%) patients achieved a complete remission and 30 (44%) a partial remission. The response rates for Rai stages 0 to 2, 3, and 4 were 64%, 58%, and 50% respectively. Seventeen (43%) of the 40 Rai stage 1 to 3 patients and four (19%) of the Rai stage 4 patients returned to Rai stage 0. Survival was strongly correlated with the final Rai stage achieved. The survival of the 11 partial responders with residual disease consisting only of residual bone-marrow nodules was similar to the complete responders (36+ months) and superior to the other partial response patients (16 months). The response to fludarabine was rapid, with 36 (92%) of the 39 responders having achieved at least a partial response following the first three courses. Complete responses occurred in the blood, liver, spleen, and lymph nodes in 48% to 69% of the patients. Eradication of all disease in the bone marrow occurred in only 13% of the cases. Neutropenia and thrombocytopenia occurred in 56% and 25% of evaluable courses. Major infections occurred in 9% of evaluable courses and fevers of unknown origin or minor infections in 12% of courses respectively. Myelosuppression and infection were more common in patients with initial Rai stages 3 and 4 and in nonresponding patients. Other toxicity was mild. No CNS toxicity was noted.

Antimetabolites, Antineoplastic↗
PubMed1988

Mechanism involved in the mobilization of neutrophil calcium by 5-hydroxyeicosatetraenoate.

5-Hydroxyeicosatetraenoate (5-HETE), like leukotriene B4 and platelet-activating factor, stimulated human polymorphonuclear neutrophils to mobilize intracellular calcium. The three compounds acted through mechanisms that were inhibited by pertussis toxin, cholera toxin, and PMA. Each agonist, furthermore, desensitized (or down-regulated) the neutrophil's calcium mobilization response to a second challenge with the same agonist. However, 5-HETE and leukotriene B4 had little or no activity in cross-desensitizing neutrophil responses to each other or to platelet-activating factor. Furthermore, 5-HETE interfered minimally or not at all with the binding of radiolabeled leukotriene B4 and platelet-activating factor to their respective receptors on neutrophils. Thus, 5-HETE mobilizes neutrophil calcium by a mechanism different from those used by leukotriene B4 and platelet-activating factor. This mechanism appears to involve specific 5-HETE receptors that couple to pertussis toxin-inhibitable, GTP-binding proteins.

Calcium↗
PubMed1988

Fludarabine therapy in chronic lymphocytic leukemia (CLL).

Fludarabine (9-beta-D-arabinofuranosyl 2-fluoro-adenine monophosphate) is a fluorinated analogue of adenine which is relatively resistant to deamination by adenosine deaminase. Phase I clinical trials disclosed significant antitumor activity in lymphoid malignancies. Fludarabine has been used in the treatment of CLL since March, 1985, at a dose of 25-30 mg/m2/day x 5 days each 3-4 weeks by short intravenous infusion. Sixty-eight previously treated patients with CLL are evaluable for response. The median age was 60 years, 50 were male the median number of prior chemotherapy regimens was 2, and the median time from initial chemotherapy to fludarabine was 45 months. Forty-three (63%) were Rai stages 3 and 4, 31 (46%) were Binet Stage C. Twenty patients (29%) obtained a complete remission (CR), defined as peripheral lymphocytes less than 4,000/microliters, no clinical evidence of disease, less than 30% of lymphocytes in the bone marrow (with no residual nodules), or a nodular partial remission, NPR (CR except for residual lymphoid nodules), and 19 (28%) a partial remission (less than 50% reduction in tumor in nodes, liver, spleen and bone marrow and greater than 1 log reduction in the lymphocyte count). The complete remission rate for the various involved sites were blood (69%), liver (52%), spleen (55%), and nodes (48%). The bone marrow was the least responsive site with 16% CR and 44% PR. The number of prior regimens did not have a significant response rate or survival. The serum albumin , alkaline phosphatase, platelet and hemoglobin level all were associated with survival from the start of fludarabine.(ABSTRACT TRUNCATED AT 250 WORDS)

Antimetabolites, Antineoplastic↗
PubMed1988

Cytogenetic features of Hodgkin's disease suggest possible origin from a lymphocyte.

Surface marker and gene rearrangement data have supported various hypotheses about the origin of the malignant cell in Hodgkin's disease. Cytogenetic data about this disorder, however, are very scanty. To determine if any chromosomal abnormalities that could add further information to this controversial point are present, we studied tumor samples from 49 patients. Abnormal metaphases were obtained in 18 cases. The most common breakpoints were in 11q23, 14q32, 6q11-21, and 8q22-24. These are common breakpoints in lymphoma and raise the possibility that the malignant cell in Hodgkin's disease may be derived from a lymphocyte. The 11q23 breakpoint is also seen in t(4;11) and t(9;11), which is typical of a type of childhood B-cell acute lymphoblastic leukemia characterized by the presence of aberrant myeloid and monocytic markers. Myeloid and monocytic markers are common in Reed-Sternberg cells.

Chromosome Aberrations↗
PubMed1987

The correlation between serum and salivary melatonin concentrations and urinary 6-hydroxymelatonin sulphate excretion rates: two non-invasive techniques for monitoring human circadian rhythmicity.

Although there is a circadian rhythm in blood melatonin concentrations in humans, the problems associated with frequent blood collection limit the use of this rhythm in the investigation of the circadian system and in the diagnosis and treatment of chronobiological disorders. Therefore, to establish a convenient, non-invasive technique for monitoring melatonin circadian rhythmicity, we compared the melatonin concentrations in blood samples collected from five subjects every 2-4 h over a 26 h period, with the melatonin concentrations in saliva samples and with the total amount of 6-hydroxymelatonin sulphate excreted in the urine during 2-h periods. There was significant correlation between serum and salivary melatonin concentrations (r = 0.81, P less than 0.001), and between serum melatonin concentrations and 6-hydroxymelatonin sulphate excretion rates (r = 0.72, P less than 0.001). The results demonstrate that both salivary melatonin concentrations and urinary 6-hydroxymelatonin sulphate excretion rates are reliable indices of serum melatonin concentrations. These measurements, in combination with frequent sample collection, provide two convenient, non-invasive techniques for monitoring melatonin circadian rhythmicity.

Adult↗
PubMed1986

Metabolism of 5-hydroxyicosatetraenoate by human neutrophils: production of a novel omega-oxidized derivative.

Human neutrophils incorporated 5-hydroxy-E,Z,Z,Z-6,8,11,14-eicosatetraenoic acid (5-HETE) into cellular triglyceride and phospholipid. They also metabolized 5-HETE into a novel, extracellularly released derivative, 5,20-dihydroxy-E,Z,Z,Z-6,8,11,14-eicosatetraenoic acid (5,20-diHETE). 5,20-diHETE formation predominated at higher substrate concentrations and longer incubation intervals. In the absence of added 5-HETE, 1 X 10(8) neutrophils stimulated with 20 microM ionophore A23187 produced up to 243 ng of 5,20-diHETE, indicating that both endogenously formed and exogenously added substrate could be oxidized at carbon 20. 5,20-diHETE was about 10- to 100-fold weaker than 5-HETE in enhancing human neutrophil degranulation responses to platelet-activating factor. omega-Oxidation appears to be a general enzymatic mechanism for inactivation of arachidonic acid metabolites.

Calcimycin↗
PubMed1986

Treatment of stages I and II Hodgkin's disease with three different therapeutic modalities.

Since 1969, 184 previously untreated and evaluable adult patients with Hodgkin's disease, staged as I (43) or II (141), have been treated. Eighty patients were part of the National Hodgkin's Disease Study, randomly assigned to receive radiotherapy to either an involved (39) or extended field (41). In a subsequent single-arm study, 104 patients were treated with involved-field radiotherapy preceded and followed by three cycles of MOPP chemotherapy. Median durations of follow-up have been 172, 172, and 92 months, for the involved-field radiotherapy, extended-field radiotherapy, and MOPP plus involved-field radiotherapy treatment groups, respectively. Although significant differences among the three treatment groups were observed with respect to disease-free survival (p less than 0.001), only the group of patients treated with involved-field radiotherapy had a statistically significant decline in overall survival as compared with the two other treatment groups (p less than 0.001). Moreover, patients who underwent clinical staging and were treated with MOPP plus involved-field radiotherapy had significantly prolonged disease-free survival compared with those who underwent surgical staging and were treated with extended-field radiotherapy (p less than 0.001). One of the patients who received MOPP plus involved-field radiotherapy had subsequent development of acute monocytic leukemia, and another had refractory anemia with excess blasts. One instance of diffuse poorly differentiated lymphocytic lymphoma was also observed. Acute monocytic leukemia developed in another patient treated with involved-field radiotherapy. The rates of amenorrhea in the group treated with MOPP plus involved-field radio-therapy were 9.6 percent and 78.5 percent for female patients younger and older than 30 years of age, respectively. Despite the universal azoospermia ensuing after MOPP plus involved-field radiotherapy, in three patients whose sperm counts were checked sequentially for 26 to 53 months after treatment, evidence of spermatogenesis was observed. Three patients with remission of Hodgkin's disease after involved-field (two) and extended-field (one) radiotherapy died from cardiovascular disease that could only be attributed to the prior radiotherapy. Although further follow-up evaluation will be required to determine the impact of the three different treatment modalities on survival and long-term toxicity, MOPP plus involved-field radiotherapy appears to be superior to involved-field or extended-field radiotherapy alone in achieving prolonged disease-free survival without significant leukemogenic potential.

Adult↗
PubMed1986

Binding and metabolism of platelet-activating factor by human neutrophils.

Human polymorphonuclear neutrophils rapidly incorporated radiolabeled platelet-activating factor, 1-O-[hexadecyl-9, 10-3H2]-2-acetyl-sn-glycero-3-phosphocholine ([3H]PAF), and then metabolized it into its sn-2-fatty acyl derivative. Fractionation of radiolabel-pretreated cells over Percoll gradients revealed that virtually all of the intact [3H]PAF was located in nongranule membranes that were enriched with alkaline phosphatase and cell surface glycoproteins. While still membrane associated, the ligand was rapidly converted to its acyl derivative and then more slowly transferred to specific granules and, to a lesser extent, azurophilic granules. In contrast, neutrophils did not metabolize [3H]PAF at 4 degrees C but rather gradually accumulated it in their alkaline phosphatase-enriched membrane subfractions. These same subfractions contained receptors for the ligand, as determined by their capacity to bind [3H]PAF specifically. Binding was readily saturated, partially reversible, and fit a two receptor model; dissociation constant (Kd) values for high and low affinity sites were 0.2 and 500 nM, respectively. Receptors with similar affinities were detected in whole cells. Furthermore, the potencies of several structural analogues in inhibiting binding of [3H]PAF to membranes correlated closely with their respective potencies in stimulating degranulation responses. Finally, quantitative studies suggested all or most of the cell's receptors were membrane associated. We conclude that PAF rapidly enters cellular membranes to bind with specific receptors that trigger function. The intramembranous ligand is also deacetylated, acylated, and then transferred to granules. This metabolism may be sufficiently rapid to limit ligand-receptor binding and distort quantitative analyses of receptors.

Binding, Competitive↗