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Biomedical subjects

C Clement

Publications and source records attributed to C Clement.

At least 19 recordsLinked to original sources
PubMed2001

Vasopressin versus epinephrine for inhospital cardiac arrest: a randomised controlled trial.

BACKGROUND: Survival rates for cardiac arrest patients, both in and out of hospital, are poor. Results of a previous study suggest better outcomes for patients treated with vasopressin than for those given epinephrine, in the out-of-hospital setting. Our aim was to compare the effectiveness and safety of these drugs for the treatment of in-patient cardiac arrest. METHODS: We did a triple-blind randomised trial in the emergency departments, critical care units, and wards of three Canadian teaching hospitals. We assigned adults who had cardiac arrest and required drug therapy to receive one dose of vasopressin 40 U or epinephrine 1 mg intravenously, as the initial vasopressor. Patients who failed to respond to the study intervention were given epinephrine as a rescue medication. The primary outcomes were survival to hospital discharge, survival to 1 h, and neurological function. Preplanned subgroup assessments included patients with myocardial ischaemia or infarction, initial cardiac rhythm, and age. FINDINGS: We assigned 104 patients to vasopressin and 96 to epinephrine. For patients receiving vasopressin or epinephrine survival did not differ for hospital discharge (12 [12%] vs 13 [14%], respectively; p50.67; 95% CI for absolute increase in survival 211.8% to 7.8%) or for 1 h survival (40 [39%] vs 34 [35%]; p50.66; 210.9% to 17.0%); survivors had closely similar median mini-mental state examination scores (36 [range 19-38] vs 35 [20-40]; p50.75) and median cerebral performance category scores (1 vs 1). INTERPRETATION: We failed to detect any survival advantage for vasopressin over epinephrine. We cannot recommend the routine use of vasopressin for inhospital cardiac arrest patients, and disagree with American Heart Association guidelines, which recommend vasopressin as alternative therapy for cardiac arrest.

Aged↗
PubMed2001

The Canadian CT Head Rule for patients with minor head injury.

BACKGROUND: There is much controversy about the use of computed tomography (CT) for patients with minor head injury. We aimed to develop a highly sensitive clinical decision rule for use of CT in patients with minor head injuries. METHODS: We carried out this prospective cohort study in the emergency departments of ten large Canadian hospitals and included consecutive adults who presented with a Glasgow Coma Scale (GCS) score of 13-15 after head injury. We did standardised clinical assessments before the CT scan. The main outcome measures were need for neurological intervention and clinically important brain injury on CT. FINDINGS: The 3121 patients had the following characteristics: mean age 38.7 years); GCS scores of 13 (3.5%), 14 (16.7%), 15 (79.8%); 8% had clinically important brain injury; and 1% required neurological intervention. We derived a CT head rule which consists of five high-risk factors (failure to reach GCS of 15 within 2 h, suspected open skull fracture, any sign of basal skull fracture, vomiting >2 episodes, or age >65 years) and two additional medium-risk factors (amnesia before impact >30 min and dangerous mechanism of injury). The high-risk factors were 100% sensitive (95% CI 92-100%) for predicting need for neurological intervention, and would require only 32% of patients to undergo CT. The medium-risk factors were 98.4% sensitive (95% CI 96-99%) and 49.6% specific for predicting clinically important brain injury, and would require only 54% of patients to undergo CT. INTERPRETATION: We have developed the Canadian CT Head Rule, a highly sensitive decision rule for use of CT. This rule has the potential to significantly standardise and improve the emergency management of patients with minor head injury.

Adolescent↗
PubMed2001

Canadian CT head rule study for patients with minor head injury: methodology for phase II (validation and economic analysis).

Prospective validation on a new set of patients is an essential test of a new decision rule. However, many clinical decision rules are not prospectively assessed to determine their accuracy, reliability, clinical sensibility, or potential impact on practice. This validation process is important because many statistically derived rules or guidelines do not perform well when tested in a new population. The methodologic standards for a validation study are similar to those described in the article on phase I for derivation studies in the August 2001 issue of Annals of Emergency Medicine. The goal of phase II is to prospectively assess the accuracy, reliability, and acceptability of the decision rule in a new set of patients with minor head injury. This will determine the clinical utility of the rule and is essential if such a rule is to be widely adopted into clinical practice.

Canada↗
PubMed2001

The Canadian CT Head Rule Study for patients with minor head injury: rationale, objectives, and methodology for phase I (derivation).

Head injuries are among the most common types of trauma seen in North American emergency departments, with an estimated 1 million cases seen annually. "Minor" head injury (sometimes known as "mild") is defined by a history of loss of consciousness, amnesia, or disorientation in a patient who is conscious and talking, that is, with a Glasgow Coma Scale score of 13 to 15. Although most patients with minor head injury can be discharged without sequelae after a period of observation, in a small proportion, their neurologic condition deteriorates and requires neurosurgical intervention for intracranial hematoma. The objective of the Canadian CT Head Rule Study is to develop an accurate and reliable decision rule for the use of computed tomography (CT) in patients with minor head injury. Such a decision rule would allow physicians to be more selective in their use of CT without compromising care of patients with minor head injury. This paper describes in detail the rationale, objectives, and methodology for Phase I of the study in which the decision rule was derived. [Stiell IG, Lesiuk H, Wells GA, McKnight RD, Brison R, Clement C, Eisenhauer MA, Greenberg GH, MacPhail I, Reardon M, Worthington J, Verbeek R, Rowe B, Cass D, Dreyer J, Holroyd B, Morrison L, Schull M, Laupacis A, for the Canadian CT Head and C-Spine Study Group. The Canadian CT Head Rule Study for patients with minor head injury: rationale, objectives, and methodology for phase I (derivation). Ann Emerg Med. August 2001;38:160-169.]

Adolescent↗
PubMed1999

Circulating CD2+ monocytes are dendritic cells.

Low levels of CD2 have been described on subsets of monocytes, macrophages, and dendritic cells. CD2 is expressed on about one-third of circulating monocytes, at levels one-half log lower than on T or NK cells, representing 2-4% of PBMC. FACS analysis of CD2+ and CD2- monocytes revealed no significant difference in the expression of adhesion molecules (CD11a/b/c), class II Ags (HLA-DR, -DQ, -DP), myeloid Ags (CD13, CD14, CD33), or costimulatory molecules (CD80, CD86). Freshly isolated CD2+ and CD2- monocytes were morphologically indistinguishable by phase contrast microscopy. However, scanning electron microscopy revealed large prominent ruffles on CD2+ monocytes in contrast to small knob-like projections on CD2- monocytes. After 2 days of culture, the CD2+ monocytes largely lost CD14 expression and developed distinct dendrites, whereas the CD2- monocytes retained surface CD14 and remained round or oval. Freshly isolated CD2+ monocytes were more potent inducers of the allogeneic MLR and more efficiently induced proliferation of naive T cells in the presence of HIV-1 gp120 than did CD2- monocytes. After culture in the presence of GM/CSF and IL-4, CD2+ monocytes were up to 40-fold more potent than monocyte-derived dendritic cells or CD2- monocytes at inducing allogeneic T cell proliferation. These findings suggest that circulating CD2+ and CD2- monocytes are dendritic cells and the precursors of macrophages, respectively. Thus, dendritic cells are far more abundant in the blood than previously thought, and they and precursors of macrophages exist in the circulation as phenotypically, morphologically, and functionally distinct monocyte populations.

Antigen Presentation↗
PubMed1999

Carotid arterial stenosis: evaluation at CT angiography with the volume-rendering technique.

PURPOSE: To determine whether computed tomographic (CT) angiography with the volume-rendering technique (VRT) can be used to accurately quantify carotid arterial stenosis and to identify occlusions. MATERIALS AND METHODS: Spiral CT was performed in 23 patients who were referred for carotid stenosis evaluation. VRT images and shaded-surface display (SSD) images of 46 carotid arterial bifurcations were compared with findings from digital subtraction angiography (DSA). RESULTS: Agreement on stenosis category between VRT CT angiography and DSA was found in 39 (85%) of the 46 carotid arteries studied. VRT CT angiography was 92% (49 of 53) sensitive and 96% (82 of 85) specific for the detection of grade 2-3 stenoses (> or = 70% stenosis). Agreement on stenosis category between SSD CT angiography and DSA was found in 38 (83%) of the 46 carotid arteries studied. SSD CT angiography was 91% (48 of 53) sensitive and 93% (79 of 85) specific for the detection of grade 2-3 stenoses. Calcified stenoses were correctly graded at VRT CT angiography in 10 of the 10 cases with heavy mural calcified plaques, while eight of the 10 stenoses were accurately quantified at SSD CT angiography. CONCLUSION: These results indicate that VRT CT angiography is as accurate as SSD CT angiography in the evaluation of carotid arterial bifurcations.

Aged↗
PubMed1999

Application of a diagnostic clinical model for the management of hospitalized patients with suspected deep-vein thrombosis.

The purpose of this study was to evaluate whether the determination of pretest probability using a simple clinical model and the SimpliRED D-dimer could be used to improve the management of hospitalized patients with suspected deep-vein thrombosis. Consecutive hospitalized patients with suspected deep-vein thrombosis, had their pretest probability determined using a clinical model and had a SimpliRED D-dimer assay. Patients at low pretest probability underwent a single ultrasound test. A negative ultrasound excluded the diagnosis of deep-vein thrombosis whereas a positive ultrasound was confirmed by venography. Patients at moderate pretest probability with a positive ultrasound were treated for deep-vein thrombosis whereas patients with an initial negative ultrasound underwent a single follow-up ultrasound one week later. Patients at high pretest probability with a positive ultrasound were treated whereas those with negative ultrasound underwent venography. All patients were followed for three months for the development of venous thromboembolic complications. Overall, 28% (42/150), and 10% (5/50), 21% (14/71) and 76% (22/29) of the low, moderate and high pretest probability patients. respectively, had deep vein thrombosis. Two of 111 (1.8%; 95% CI = 0.02% to 6.4%) patients considered to have deep vein thrombosis excluded had events during three-month follow-up. Overall 13 of 150 (8.7%) required venography and serial testing was limited to 58 of 150 (38.7%) patients. The negative predictive value of the SimpliRED D-dimer in patients with low pretest probability was 96.2%, which is not statistically different from the negative predictive value of a negative ultrasound result in low pretest probability patients (97.8%). Management of hospitalized patients with suspected deep-vein thrombosis based on clinical probability and ultrasound of the proximal deep veins is safe and feasible.

Cohort Studies↗
PubMed1998

Dispelling the myths of CPR.

Without a "do not attempt resuscitation" order on a patient's chart, nurses are obliged to initiate cardiopulmonary resuscitation (CPR) on all patients who die in hospital. Their discomfort with this situation is often related to the perception that resuscitation attempts are being carried out, at best, inappropriately and, at worst, unethically.

Cardiopulmonary Resuscitation↗
PubMed1996

Anti-gp130 transducer monoclonal antibodies specifically inhibiting ciliary neurotrophic factor, interleukin-6, interleukin-11, leukemia inhibitory factor or oncostatin M.

Five cytokines activate the gp130 IL-6 transducer: ciliary neurotrophic factor, interleukin-6, interleukin-11, leukemia inhibitory factor and oncostatin M. Human plasmacytoma cell lines, completely dependent on the addition of one of these five cytokines for their growth, were used to obtain anti-gp130 monoclonal antibodies specifically inhibiting one of these five cytokines without affecting the biological activity of the others. These antibodies should improve our understanding of the interaction of gp130 transducer using cytokines with gp130 transducer and facilitate the design of new cytokine inhibitors.

Antibodies, Monoclonal↗
PubMed1995

Functional distinction of two regions of human interleukin 6 important for signal transduction via gp130.

Mutagenesis of a region of human interleukin (IL)-6 which is important for triggering signal transduction via the IL-6 receptor beta-chain (gp130) has lead to the isolation of a variant of human IL-6 (IL-6.Q160E/T163P), which could antagonize the biological activity of wild type IL-6 on the human EBV transformed B cell line CESS and the human hepatoma cell line HepG2. Surprisingly this antagonistic IL-6 variant had an agonistic effect on the human myeloma cell line XG-1, albeit at a 1000-fold higher concentration than wild type IL-6. This residual activity of the mutant arose from triggering gp130, because it could be inhibited by a gp130 specific mAb. Extensive mutagenesis of residues between Q153 and H165 of human IL-6, a region which is partly homologous in cytokines which also signal via gp130 (oncostatin M, ciliary neurotrophic factor, leukaemia inhibitory factor, IL-11), did result in the isolation of a second antagonist for IL-6 activity on CESS and HepG2 cells. However on XG-1 cells this variant was active as well. These results suggest that (an) additional region(s) of the IL-6 molecule might be involved in gp130 triggering. Recently we indeed found that residues Lys42-Ala57 are also important for gp130 triggering. Inhibition experiments with neutralizing IL-6R alpha-chain specific mAb show that this region can be functionally separated from the Q153-H165 region. These findings have important implications for the development of receptor antagonists of IL-6 and IL-6 family members.

Alanine↗
PubMed1995

Increased number of high sensitive platelets in hypercholesterolemia, cardiovascular diseases, and after incubation with cholesterol.

The number of low density platelets was found to be increased in patients with hypercholesterolemia, as compared with the number in controls. The percentage increase of the low density platelet subpopulation was even more pronounced in patients with hypercholesterolemia when compared with that in patients suffering from myocardial infarction or angina. In vitro studies with control platelets incubated with cholesterol rich liposomes showed also an increase in the subpopulation of low density platelets. After incubation of control platelets with cholesterol rich liposomes, a higher membrane anisotropy and a higher cholesterol to phospholipid (C/P) molar ratio of the plasma membrane were found. Furthermore, cholesterol-enriched platelets were more sensitive upon thrombin stimulation. The results suggest that a shift of platelet subpopulations to a higher number of low density platelets could be caused by either the level of plasma cholesterol or an in-vitro incubation with cholesterol rich liposomes.

Analysis of Variance↗
PubMed1995

Circulating interleukin-6 receptor in patients with sepsis syndrome.

Concentrations of interleukin (IL)-6, soluble IL-6 receptor (sIL-6R), and soluble tumor necrosis factor receptor (sTNFR) p55 and p75 were measured in 25 patients with sepsis syndrome. Sequential blood samples were drawn from patients during a 7-h period. IL-6 concentrations were 34-763,000 pg/mL; they were higher in nonsurvivors than survivors, but the difference was not statistically significant. In septic patients, the median sIL-6R concentration was significantly lower than in 19 healthy volunteers (43 vs. 80 ng/mL). sIL-6R concentrations in survivors were not significantly different than those in nonsurvivors. There was a negative correlation between IL-6 and sIL-6R in septic patients (r = -.72). In patients with moderately impaired renal function, sIL-6R levels were not affected, but the concentrations of sTNFRs were significantly higher.

Adolescent↗
PubMed1995

[Leiomyosarcoma of the inferior vena cava. Apropos of a new case].

A leiomyosarcoma was diagnosed in the mid portion of the inter-renal inferior vena cava. Survival was long (6 years) but required 14 reoperations to remove metastases. During the first operation, vascular integrity was reestablished with a cava-cava prosthesis after exeresis of the upstream cava without removal of the left renal vein ostium. The right renal vein was sectioned and directly implanted onto the prosthesis. The pathology report confirmed the diagnosis of leiomyosarcoma with multiple metastases presenting cytonuclear anomalies which worsened with time.

Blood Vessel Prosthesis↗
PubMed1994

Role of IL-6 in promoting growth of human EBV-induced B-cell tumors in severe combined immunodeficient mice.

To investigate the role of IL-6 as a growth factor in EBV-induced B lymphoproliferative disorders in immune-suppressed patients, we analyzed two B cell lines derived from two different patients for IL-6 production, expression of the p80 chain of the IL-6 receptor, and the effects on cell growth in vitro and in vivo of neutralizing mAbs specific for IL-6. One of the cell lines (LCL41) was shown to produce large amounts of IL-6 and to express IL-6 receptors. Its in vitro growth was weakly inhibited by the anti-IL-6 MAb. After inoculation into SCID mice, this cell line provoked human B cell tumors, the growth of which was controlled by the anti-IL-6 mAb. Indeed, four i.v. infusions of 0.1 mg at days 30 to 42 after i.p. inoculation of cells led to complete remission in most mice and long term survival in 40% of cases. In contrast, the other B cell line (LCL48) produced smaller amounts of IL-6; its growth was not inhibited in vitro by the anti-IL-6 Ab and was poorly blocked in vivo in SCID mice (40% of remissions and 20% of long-term survival). In addition, a clone derived in vivo in SCID mice from LCL48 was completely IL-6-independent. These results demonstrate that B cell tumors transformed in vivo by EBV in immune-suppressed patients are heterogeneous with respect to IL-6 requirements for proliferation. An antitumoral effect in some of them can be achieved by neutralizing the IL-6-dependent proliferative loop.

Animals↗
PubMed1992

Erythropoietin in continuous ambulatory peritoneal dialysis: experience with subcutaneous administration.

Experience in the use of subcutaneous erythropoietin (EPO) in 32 continuous ambulatory peritoneal dialysis (CAPD) patients is presented. All patients were treated with oral iron supplements. The total and mean +/- SD durations of EPO treatment were 466 weeks and 14.6 +/- 10.1 weeks respectively. Twenty-two patients started treatment with normal or elevated iron stores; 10 had an initial iron saturation less than 20%. The initial hematocrit was 23.8 +/- 3.7%. Thirteen patients reached a steady-state hematocrit by the end of the study period, when the mean +/- SD hematocrit for all 32 patients was 34.1 +/- 3.6%. All patients responded to EPO. The initial dose of EPO was 147.1 +/- 53.8 U/kg/week. Maintenance dose was 72 +/- 36 U/kg/week.

Anemia↗
PubMed1991

Murine anti-interleukin-6 monoclonal antibody therapy for a patient with plasma cell leukemia.

A patient with primary plasma cell leukemia resistant to chemotherapy was treated for 2 months with daily intravenous injections of anti-interleukin-6 (IL-6) monoclonal antibodies (MoAbs). The patient's clinical status improved throughout the treatment and no major side effects were observed. Serial monitoring showed blockage of the myeloma cell proliferation in the bone marrow (from 4.5% to 0% myeloma cells in the S-phase in vivo) as well as reduction in the serum calcium, serum monoclonal IgG, and the serum C-reactive protein levels. The serum calcium and serum monoclonal IgG corrected by approximately 30%, whereas the C-reactive protein corrected to undetectable levels during treatment. No major side effects developed, although both platelet and circulating neutrophil counts decreased during anti-IL-6 therapy. A transient immunization was detected 15 days after the initiation of the treatment, which could explain the recovery of myeloma cell proliferation after 2 months of treatment (2% myeloma cells in the S phase). In conclusion, this first anti-IL-6 clinical trial demonstrated the feasibility of injecting anti-IL-6 MoAbs, and also a transient tumor cytostasis and a reduction in IL-6-related toxicities. It gave insight into the major biologic activities of IL-6 in vivo and may serve as a basis for further development of anti-IL-6 therapy in myeloma and other IL-6-related diseases.

Acute-Phase Proteins↗