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Biomedical subjects

P Stevens

Publications and source records attributed to P Stevens.

At least 55 records · Page 3Linked to original sources
PubMed1995

Antiphospholipid antibodies and venous thromboembolism.

The clinical relevance of antiphospholipid antibodies (APLA) in patients without systemic lupus erythematosus who have venous thromboembolism (VTE) in unknown. Limited evidence suggests that there is an association between the presence of APLA and both initial and recurrent episodes of VTE and that patients with APLA and VTE are resistant to warfarin therapy. Unselected patients with a first episode of clinically suspected deep vein thrombosis or pulmonary embolism were evaluated with objective tests for VTE and with laboratory tests for APLA; the latter included tests for the lupus anticoagulant (LA) and anticardiolipin antibodies (ACLA). Patients with VTE were treated with anticoagulant therapy and observed during and after discontinuation of anticoagulants for symptomatic recurrence of VTE. There was a strong association between LA and VTE (odds ratio, 9.4; 95% confidence interval [CI], 2.1 to 46.2) and 9 to 65 (14%; 95% CI, 7% to 25%) patients with VTE had LA. There was no association between the presence of ACLA and VTE (odds ratio, 0.7; 95%CI, 0.3 to 1.7) because of the high frequency of positive ACLA assays in patients without VTE. None of the 16 patients with VTE and APLA developed recurrent VTE while receiving warfarin therapy. There was no difference in rates of recurrent VTE in patients with or without APLA after anticoagulant therapy was discontinued. The strong association between LA and VTE suggests that testing for LA in patients with VTE is useful. The measurement of ACLA in patients with VTE has no clinical usefulness because the results are abnormal in a high proportion of patients without VTE. Although the presence of APLA in patients with VTE was not associated with resistance to a conventional intensity of warfarin or an increased risk of recurrent VTE after discontinuation of warfarin, a larger study should address these issues in a subgroup of patients with VTE and LA.

Adolescent↗
PubMed1995

Effect of granulocyte colony-stimulating factor treatment on ex vivo blood cytokine response in human volunteers.

We explored the ex vivo alteration in the cytokine release of stimulated blood taken from healthy volunteers treated subcutaneously with 480 micrograms granulocyte colony-stimulating factor (G-CSF). In a double-blind, controlled, randomized study with 21 volunteers who received G-CSF once or twice 24 hours apart, we measured lipopolysaccharide (LPS)-inducible release of various cytokines and soluble receptors at different times after treatment. At day 1 after a single dose of G-CSF, mediator release was also initiated with muramyl dipeptide, Staphylococcus aureus enterotoxin A, lipoteichoic acid, streptolysin O, complement factor C5a, phytohemagglutinin, or phorbol myristate acetate. In blood from G-CSF-treated subjects, our major findings were (1) a maximal 12-fold increase in interleukin-1 receptor antagonist (IL-1ra) release and an increase of both the p55 and p75 soluble tumor necrosis factor (TNF) receptors; (2) a reduction in TNF release when using all the various stimuli described except LPS; (3) an increase in G-CSF and, to lesser extent, in IL-6, IL-8, and IL-10 release; and (4) an attenuation of interferon-gamma (IFN-gamma) and granulocyte-macrophage (GM)-CSF release. Our findings demonstrate that the major effect of G-CSF treatment is a change in the responsiveness of blood towards a variety of stimuli, which we interpret as a shift toward an antiinflammatory cytokine response.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1995

A novel and rapid whole-blood assay for D-dimer in patients with clinically suspected deep vein thrombosis.

BACKGROUND: The clinical utility of using a novel whole blood assay for D-dimer (SimpliRED), alone or in combination with impedance plethysmography (IPG), was investigated in a two-center, prospective cohort study of 214 consecutive patients with clinically suspected deep vein thrombosis (DVT). METHODS AND RESULTS: All patients underwent the SimpliRED D-dimer assay, contrast venography, and IPG. According to the results of venography, 43 patients had proximal DVT (popliteal and/or more proximal veins), 10 had isolated calf DVT, and 161 had DVT ruled out. The D-dimer had a sensitivity of 93% for proximal DVT and of 70% for calf DVT, an overall specificity of 77%, and a negative predictive value of 98% for proximal DVT. The sensitivity and specificity of IPG for proximal DVT were 67% and 96%, respectively. When analyzed in combination with the IPG results, it was determined that (1) the combination of a negative D-dimer and a normal IPG had a negative predictive value of 97% for all DVT and of 99% for proximal DVT and occurred in 58% of patients (likelihood ratio, 0.1) and (2) the combination of a positive D-dimer and an abnormal IPG had a positive predictive value of 93% for any DVT and of 90% for proximal DVT and occurred in 14% of patients (likelihood ratio, 42.6). When the D-dimer and IPG results were discordant, it was not possible to exclude or diagnose DVT reliably; discordant results occurred in 28% of patients. CONCLUSIONS: The SimpliRED D-dimer assay, which can be performed and interpreted at the bedside within 5 minutes, has great potential in patients with clinically suspected DVT, especially for ruling out DVT, and is complementary to IPG. The assay should be evaluated in large clinical management studies.

Agglutination Tests↗
PubMed1995

Protective effects of a novel 32-amino acid C-terminal fragment of CAP18 in endotoxemic pigs.

BACKGROUND: Cationic antimicrobial protein of 18 kd (CAP18) is a neutrophil-derived peptide that binds lipopolysaccharide (LPS) with high affinity. We hypothesized that CAP18(106-137), a novel synthetic 32-amino acid C-terminal fragment of CAP18, would neutralize the physiologic derangements induced by LPS in anesthetized swine. METHODS: Pigs were randomly allocated into three groups. Those in the LPS group (n = 6) were infused with LPS (3 micrograms/kg/hr for 4 hours). Pigs in the LPS/CAP18 group (n = 6) were challenged with LPS (3 micrograms/kg/hr for 4 hours) and also treated with CAP18(106-137) (4 mg/kg/hr for 4 hours). Pigs in the RL group (n = 4) received neither LPS nor CAP18(106-137). RESULTS: Treatment with CAP18(106-137) blocked LPS-induced increases in plasma levels of 6-keto-prostaglandin F1 alpha and tumor necrosis factor-alpha and prevented LPS-induced changes in cardiac output, arterial PO2, phagocyte activation, and peripheral leukocyte count. Changes in circulating concentrations of thromboxane B2, mean pulmonary artery pressure, and dynamic pulmonary compliance were attenuated in the LPS/CAP18 group. CONCLUSIONS: Treatment with CAP18(106-137) neutralizes many of the deleterious effects of LPS in pigs.

6-Ketoprostaglandin F1 alpha↗
PubMed1995

Demographics of cardiac arrest: association with residence in a low-income area.

OBJECTIVE: To report cardiac arrest demographics and assess whether arrest rate is associated with differences in intracity regional population densities, incomes, or race distributions. METHODS: One-year retrospective review of out-of-hospital cardiac arrests in a city with a two-tier emergency medical service (EMS) system. Associations of population density, median income, and race data with age- and gender-adjusted cardiac arrest rates for seven city regions and groupings of high- and low-income census tracts were made. RESULTS: Median income, but not race or population density, was associated with sex- and age-adjusted intracity regional cardiac arrest rates (p = 0.034). This association of cardiac arrest rate with income status was magnified when the 20 lowest and the 20 highest income census tracts were compared. Cardiac arrest victims in these two income groups did not differ in regard to rate of witnessed arrest, bystander-administered CPR, or previous cardiac disease. Rates of survival to hospital discharge were not significantly different between the two groups. CONCLUSION: The association of lower income with cardiac arrest suggests that cardiac health promotion and EMS intervention measures, including CPR instruction, should be targeted to lower-income neighborhoods. These findings may help explain previous studies suggesting a racial or population density association with cardiac arrest rates.

Cardiopulmonary Resuscitation↗
PubMed1995

HIV seroprevalence in emergency department patients: Portland, Oregon, 1988-1991.

OBJECTIVES: In Portland, OR: 1) to determine the changes in HIV seroprevalence for ED patients from 1988 to 1991, 2) to define the characteristics of the HIV-positive ED patient, 3) to determine the hepatitis B seroprevalence of HIV-seropositive ED patients, and 4) to demonstrate the feasibility of an ED population-based surveillance investigation. METHODS: A prospective, multiyear observational, cross-sectional, multicenter, population-based seroprevalence study was performed using seven urban hospital EDs. Serologic testing for HIV and hepatitis B was performed on excess blood obtained from ED patients. Four sampling periods were used at each hospital at 14-month intervals starting June 1988 and ending December 1991. The blood specimens were obtained concurrently at all the participating hospitals. RESULTS: Of 1,681 patients, 17 (1.0%) were HIV-positive. The HIV seroprevalence rate was relatively stable over time: 0.5% (2/444) in 1988, 1.7% (7/396) in 1989, 1% (3/296) in 1990, and 0.9% (5/545) in 1991. Most (94%) HIV patients were men, 100% were white, 81% were > or = 30 years old. Most (59%) of the HIV-positive patients also were positive for hepatitis B core antibody. Many (76%) of the HIV-positive patients were known to be positive by the emergency health care worker. CONCLUSION: HIV seroprevalence among the ED patients in Portland, OR, was generally stable from 1988 to 1991. Many HIV-positive patients also were hepatitis B-positive, thus representing a double occupational infectious disease risk to ED personnel. A significant minority (24%) of the HIV-positive patients were not known to be HIV-positive by the ED personnel. Universal precautions and hepatitis B immunization are paramount for reducing the risk of infectious disease due to exposure to body fluids.

Adult↗
PubMed1995

Dissociation of cytolysis and monokine release by bovine mononuclear phagocytes incubated with Pasteurella haemolytica partially purified leukotoxin and lipopolysaccharide.

The bovine respiratory pathogen Pasteurella haemolytica secretes an exotoxin that is specific for ruminant leukocytes (leukotoxin). Previous studies have shown that subcytolytic concentrations of the leukotoxin stimulate bovine neutrophils to undergo a respiratory burst and degranulate. Relatively little is known about the stimulatory effects of the leukotoxin on bovine mononuclear phagocytes. In this study, we compared the relative cytolytic effects of partially purified leukotoxin on bovine peripheral blood monocytes and alveolar macrophages. We found monocytes to be approximately 8- to 10-fold more sensitive than alveolar macrophages to the cytolytic effect of leukotoxin. In addition, incubation of monocytes and alveolar macrophages with sublethal doses of leukotoxin stimulated release of IL-1 and TNF activities in a dose-dependent manner. Addition of an antileukotoxin MAb neutralized the cytolytic effects of leukotoxin, but potentiated TNF release. Heat inactivation also blocked the cytolytic activity of LKT, but only slightly reduced its ability to stimulate TNF release. Although the leukotoxin preparations were estimated to have only small amounts of lipopolysaccharide (LPS) contamination, as determined by a standard Limulus amebocyte lysate coagulation assay, a chromogenic Limulus assay indicated much greater amounts of LPS were present. Adding equivalent doses of P. haemolytica LPS largely duplicated the monokine release stimulated by leukotoxin. These results suggest that the stimulatory effects of the P. haemolytica leukotoxin on bovine mononuclear phagocytes may principally involve LPS, perhaps complexed with leukotoxin.

Animals↗
PubMed1995

Evaluation of a soluble fibrin assay in patients with suspected deep vein thrombosis.

BACKGROUND: The objective of this study was to determine the clinical utility of an enzyme immunoassay (EIA) for soluble fibrin in patients with clinically suspected deep vein thrombosis (DVT). METHODS AND RESULTS: 101 unselected patients with clinically suspected DVT underwent blood sampling for measurement of plasma levels of soluble fibrin, and objective testing for DVT. According to results of the objective tests, patients were classified as DVT-positive (n = 34) or DVT-negative (n = 67). Using different cut-points of soluble fibrin results, the sensitivities, specificities, positive and negative predictive values of the soluble fibrin assay were calculated. A soluble fibrin result of < or = 0.75 mg/ml showed a sensitivity and negative predictive value of 100%, and a specificity of 17.9% for DVT, a soluble fibrin result of < or = 1.40 mg/ml showed a sensitivity of 91.2% and a negative predictive value of 93.6%, and a specificity of 65.7% for DVT, whereas a soluble fibrin result of < or = 8.0 mg/ml showed a specificity and positive predictive value of 100% for DVT. CONCLUSIONS: This study demonstrates that the soluble fibrin assay used in the study has potential clinical utility as a diagnostic test in patients with clinically suspected DVT and supports further evaluation of this assay.

Evaluation Studies as Topic↗
PubMed1994

Synthesis and secretion of plasmalogens by type-II pneumocytes.

Alveolar surfactant (exposed to air and therefore a prime target of air oxidants) is supplied with antioxidants during its intracellular formation on type-II pneumocytes [Rüstow, Haupt, Stevens and Kunze (1993) Am. J. Physiol. 265, L133-L139]. Plasmalogens can protect animal cells against lipid peroxidation caused by u.v. radiation. It has been suggested that plasmalogens play a direct role in protecting animal cell membranes against oxidative stress [Zoeller, Morand and Raetz (1988) J. Biol. Chem. 263, 11590-11596]. We investigated biosynthesis and secretion of plasmalogens and phospholipids by type-II cells of adult rat lungs. The plasmalogens of type-II cells consist of 93% ethanolamine plasmalogens (EthPlas) and 7% choline plasmalogens (ChoPlas). Plasmalogens isolated from alveolar surfactant, however, consist of 36.5% ChoPlas and 63.5% EthPlas. The different incorporation rates of [14C]hexadecanol into both types of plasmalogen by type-II pneumocytes are reflected in the relative proportions of their total cellular plasmalogen content. Type-II cells cultured in the presence of labelled hexadecanol or labelled hexadecylglycerol and of labelled palmitate secrete labelled ChoPlas and labelled phospholipids, both spontaneously and in response to isoprenaline. The spontaneous and stimulated secretion rates of labelled ChoPlas are 3-6 times higher than those of labelled EthPlas. This higher relative secretion rate of ChoPlas corresponds to its higher proportion in the total plasmalogen content of alveolar surfactant compared with type-II cells. Added extracellular surfactant-specific protein A inhibits the secretion of plasmalogens as well as that of phospholipids by type-II cells. The molecular species of EthPlas and ChoPlas isolated from type-II cells or lung lavage do not differ significantly and consist mainly of molecular species containing poly-unsaturated fatty acids. We conclude that ChoPlas are secreted partly as integral constituents of the alveolar surfactant. Type-II cells select between both types of plasmalogens for secretion as a constituent of surfactant. The intramolecular sorting signal presumably is the choline moiety.

Animals↗
PubMed1994

Reevaluation of the sensitivity of impedance plethysmography for the detection of proximal deep vein thrombosis.

BACKGROUND: To reevaluate the sensitivity of impedance plethysmography (IPG) for proximal deep vein thrombosis (DVT) and to establish a relationship between the location and size of thrombi and the results of IPG. DESIGN: Prospective cohort study. METHODS: One hundred thirty-two consecutive patients with clinically suspected DVT underwent IPG testing and most (n = 118) underwent contrast-enhanced venography; in 14 patients, venous ultrasonography was performed and demonstrated definitive proximal DVT in which the size and extent of the thrombus could be delineated. All patients with dubious or normal ultrasound results underwent contrast-enhanced venography. All tests were performed and test results were interpreted without knowledge of the results of the other tests. Patients were considered to have proximal DVT if this was demonstrated on venography or ultrasound, calf DVT if this was demonstrated on venography, or no DVT if venography yielded normal findings. The sensitivity and specificity of IPG for DVT were calculated. RESULTS: Of the 132 patients, 40 (30%) had proximal DVT, seven (5%) had calf DVT, and 85 (64%) had no DVT. The sensitivity of IPG for proximal DVT was 65% and the specificity was 93%. Of the proximal vein thrombi, IPG detected three (23%) of 13 that involved the popliteal vein but not the superficial femoral vein and 23 (85%) of 27 proximal vein thrombi that involved the superficial femoral vein. CONCLUSIONS: Our study demonstrated that the sensitivity of IPG for proximal DVT at our center is only 65%, a figure that is much lower than those reported in earlier studies from our institution. We hypothesize that because of a change in referral practice, an increased proportion of patients with less severe symptoms are now referred to our center than in the past. These patients have thrombi that are smaller, less likely to be occlusive, and therefore less likely to yield abnormal IPG findings.

Adult↗
PubMed1994

Use of Hirulog in the prevention of venous thrombosis after major hip or knee surgery.

BACKGROUND: The study objective was to determine whether Hirulog, a direct thrombin inhibitor, has potential efficacy and safety in the prevention of deep vein thrombosis (DVT) in orthopedic patients. A phase 2 open-label, dose-escalating design was used to study 222 unselected patients undergoing major hip or knee surgery in tertiary-care, university-affiliated hospitals. METHODS AND RESULTS: Subcutaneous Hirulog was initiated postoperatively. Patients were evaluated for bleeding and symptomatic pulmonary embolism, and mandatory bilateral venography was performed before discharge. Dose escalations were made on the basis of observed rates of bleeding and venous thrombosis. There were five dosage regimens used: 0.3 mg/kg every 12 hours, 0.6 mg/kg every 12 hours, 1.0 mg/kg every 12 hours for 3 days followed by 0.6 mg/kg every 12 hours for up to 11 days, 1.0 mg/kg every 12 hours, and 1.0 mg/kg every 8 hours. One hundred seventy-seven patients who had technically adequate bilateral venography or objectively documented pulmonary embolism were included in the primary analysis of efficacy. The highest dosage regimen (1.0 mg/kg every 8 hours) provided the lowest rates of total DVT (17%) and proximal DVT (2%), both of which were significantly lower (P = .010 and P = .023, respectively) than the pooled rates of total (43%) and proximal (20%) DVT seen with the first four regimens. Bleeding rates were low (< 5%) with all regimens. CONCLUSIONS: This study demonstrates that 1.0 mg/kg Hirulog every 8 hours started postoperatively is potentially efficacious and safe for the prevention of DVT after major hip or knee surgery.

Aged↗
PubMed1994

Meralgia paresthetica in children.

We reviewed the findings in twenty children and adolescents who had meralgia paresthetica, a common entity in adults that has only rarely been reported in children. Ten patients had bilateral involvement; thus, the study included thirty lesions. Twenty-four lesions were eventually treated with open decompression of the lateral femoral cutaneous nerve; the results of twenty-one of these operations were followed for at least two years. The presenting symptom was severe pain resulting in marked restriction of activities. The pain could be reproduced with palpation of the nerve, and a trial injection of Xylocaine (lidocaine) always produced transient relief of symptoms. The average age at the onset of the symptoms was ten years (range, one to seventeen years); the diagnosis was missed initially in ten patients, which resulted in multiple, unnecessary diagnostic tests being done. The average duration of the symptoms before the patient was first seen was twenty-four months (range, two to eighty-four months), and the average duration of follow-up after the twenty-one operations was thirty-eight months (range, twenty-five to sixty months). Fourteen of the twenty-one operations led to an excellent result, with complete relief of pain and no restriction of activities; five led to a good result, with occasional pain but no limitation of sports or other activities; and two led to a fair result, with pain that interfered with sports activities but not with walking. We believe that meralgia paresthetica is much more common in children than has been previously recognized.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1994

Effects on thrombin generation of single injections of Hirulog in patients with calf vein thrombosis.

STUDY OBJECTIVE: To determine whether single injections of Hirulog, a direct thrombin inhibitor, can inhibit thrombin generation in patients with calf vein thrombosis and, if so, if the inhibition is sustained. DESIGN: Phase II open label cohort study. SETTING: Tertiary-care referral centres, university affiliated hospitals. PATIENTS: 10 patients with venographically-demonstrated calf vein thrombosis. INTERVENTION: Patients received a single injection of Hirulog, either 1.0 mg/kg subcutaneously or 0.6 mg/kg as a 15 min intravenous infusion. Prothrombin fragment (F1++2) levels, as an index of thrombin generation, were measured before as well as 6 h post- and 24 h post-Hirulog administration. Patients were followed with non-invasive tests to detect thrombus extension into the proximal veins. RESULTS: There was a significant reduction in the levels of F1+2 with both regimens, 6 h after Hirulog. The F1+2 levels 24 h post-Hirulog showed a significant increase relative to the 6 h post-Hirulog results. One patient developed thrombus extension into the popliteal vein and was treated with conventional anticoagulants. CONCLUSION: The single injections of Hirulog used in the study produced incomplete and temporary suppression of F1+2. Complete and permanent inhibition of thrombin generation with Hirulog in patients with calf vein thrombosis may require higher doses, multiple subcutaneous injections and/or prolonged intravenous infusion.

Aged↗
PubMed1993

Recombinant human protease nexin-1 prevents articular cartilage-degradation in the rabbit.

Cartilage degradation is mediated by activated matrix metalloproteinases (MMP). Since the plasmin/plasminogen cascade may activate latent MMP during cartilage catabolism, we determined if protease nexin-1 (PN-1), an inhibitor of plasminogen, plasmin, and urokinase could prevent cartilage degradation. Using a rabbit model, we induced cartilage glycosaminoglycan (GAG) loss by intraarticular (IA) injection of IL-1 beta and bFGF. PN-1 was given IA for 4 days, once before IL-1 beta/bFGF and daily for 3 days. Three days after IL-1 beta/bFGF, we determined GAG loss. PN-1 significantly inhibited GAG loss at 2.8, 2.5 mg, and 2.0 mg/knee (p < 0.03). These data suggest the role of the plasmin/plasminogen enzymatic cascade in the cartilage catabolism that occurs during IL-1-induced inflammation and demonstrates the potential of PN-1 to prevent cartilage degradation.

Amyloid beta-Protein Precursor↗