Ultrasonographic screening for deep vein thrombosis following arthroplasty fails to reduce posthospital thromboembolic complications: the Postarthroplasty Screening Study (PASS).
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Aged↗
Biomedical subjects
D R Anderson
Publications and source records attributed to D R Anderson.
Oral anticoagulants: mechanism of action, clinical effectiveness, and optimal therapeutic range.
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Administration, Oral↗
Factors associated with retrobulbar hemodynamic measurements at variable intraocular pressure.
PURPOSE: The authors determine those clinical variables that influence color Doppler measurements at spontaneous and artificially elevated intraocular pressure (IOP). METHODS: Color Doppler peak systolic velocity (PSV), end diastolic velocity (EDV), and Pourcelot ratio (PR) were measured in the central retinal artery (CRA) and posterior ciliary artery (PCA) at spontaneous IOP and artificially elevated IOP of 30 mmHg, 40 mmHg, and after release of suction-induced pressure elevation in 33 eyes of 33 patients. Those with varied ocular and systemic backgrounds were enrolled to facilitate determination of relationships between these hemodynamic measures at elevated IOP and multiple patient characteristics including the degree of glaucomatous damage. RESULTS: Intraocular pressure elevation reduced velocity and increased Pourcelot ratio in both vessels at 30 mmHg and at 40 mmHg. On release of suction-induced IOP elevation, velocity increased above the velocity measured at spontaneous IOP (hyperemic response). Blood pressure consistently correlated with velocity and with PR in both vessels at all IOP levels tested. The change in velocity with IOP challenge decreased with age, and increased with vertical cup-to-disc ratio in the CRA, and decreased with ocular beta-blocker use in the PCA. CONCLUSION: Because blood pressure and age relate to velocity, studies comparing cohorts with respect to disease or drug effects should be matched for these variables. While it is clear that the presence of glaucoma and use of beta-blockers correlate with vascular parameters, from this study it is not possible to distinguish pathogenic factors from pathologic results of disease or drug effects.
Adrenergic beta-Antagonists↗
Accuracy of screening compression ultrasonography and clinical examination for the diagnosis of deep vein thrombosis after total hip or knee arthroplasty.
OBJECTIVE: To determine whether compression ultrasonography or clinical examination should be considered as screening tests for the diagnosis of deep vein thrombosis (DVT) after total hip or knee arthroplasty in patients receiving warfarin prophylaxis postoperatively. DESIGN: A prospective cohort study. SETTING: A single tertiary care orthopedic centre. PATIENTS: One hundred and eleven patients who underwent elective total hip or knee arthroplasty were enrolled. Postoperatively the warfarin dose was adjusted daily to maintain the international normalized ratio between 1.8 and 2.5. Eighty-six patients successfully completed the study protocol. INTERVENTION: Before they were discharged from hospital, patients were assessed for DVT by clinical examination, bilateral compression ultrasonography of the proximal venous system and bilateral contrast venography. RESULTS: DVT was found in 29 patients (34%; 95% confidence interval [CI] 24% to 45%), and 6 patients (7%; 95% CI 3% to 15%) had proximal DVT. DVT developed in 18 (40%) of 45 patients who underwent total knee arthroplasty and in 11 (27%) of 41 patients who underwent total hip arthroplasty. The sensitivity of compression ultrasonography for the diagnosis of proximal DVT was 83% (95% CI 36% to 99%) and the specificity was 98% (95% CI 91% to 99%). The positive predictive value of compression ultrasonography was 71%. In contrast, clinical examination for DVT had a sensitivity of 11% (95% CI 2% to 28%) and a positive predictive value of 25%. CONCLUSIONS: DVT is a common complication after total hip or knee arthroplasty. Compression ultrasonography appears to be a relatively accurate noninvasive test for diagnosing postoperative proximal DVT. In contrast, clinical examination is a very insensitive test. Whether routine use of screening compression ultrasonography will reduce the morbidity of venous thromboembolism after joint arthroplasty requires confirmation in a prospective trial involving long-term follow-up of patients.
Aged↗
Ultrasonographic screening before hospital discharge for deep venous thrombosis after arthroplasty: the post-arthroplasty screening study. A randomized, controlled trial.
BACKGROUND: The clinical significance of asymptomatic deep venous thrombosis that develops after joint arthroplasty and the value of screening tests to detect thrombi are uncertain. OBJECTIVES: To determine 1) the rate of symptomatic deep venous thrombosis or pulmonary embolism occurring after hospitalization for joint arthroplasty and 2) the value of screening compression ultrasonography. DESIGN: Double-blind, randomized, controlled trial. SETTING: Tertiary care hospital. PATIENTS: 1024 patients undergoing elective total hip or knee arthroplasty who received warfarin prophylaxis. INTERVENTION: Patients were randomly assigned to undergo either bilateral compression ultrasonography or a sham procedure before hospital discharge. Patients with a diagnosis of asymptomatic deep venous thrombosis were treated after discharge with standard anticoagulant therapy; other patients had warfarin therapy discontinued at discharge. All patients were followed for 90 days. RESULTS: In the screening group, asymptomatic proximal deep venous thrombosis was detected in 13 of 518 patients (2.5%). Another 4 patients subsequently developed symptomatic proximal deep venous thrombosis, and 1 patient treated for asymptomatic deep venous thrombosis developed major bleeding, for a total outcome event rate of 1.0% (5 of 518 patients). In the placebo group, 3 patients developed symptomatic proximal deep venous thrombosis and 2 had nonfatal pulmonary embolism, for a total event rate of 1.0% (5 of 506 patients) (difference, 0 percentage points [95% CI, -1.2 to 1.2 percentage points]). CONCLUSIONS: In patients undergoing total hip or knee arthroplasty, the use of warfarin prophylaxis during hospitalization results in a very low rate of symptomatic deep venous thrombosis or pulmonary embolism after hospital discharge. The use of screening compression ultrasonography at hospital discharge does not seem to be justified in this setting.
Algorithms↗
Enoxaparin as prophylaxis against thromboembolism after total hip replacement.
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Anticoagulants↗
In vitro mutational and inhibitory analysis of the cis-acting translational elements within the 5' untranslated region of coxsackievirus B3: potential targets for antiviral action of antisense oligomers.
The 5' untranslated region (5'UTR) of coxsackievirus B3 (CVB3) RNA forms a highly ordered secondary structure that has been implicated in controlling initiation of viral translation by internal ribosomal entry. To test this hypothesis, synthetic bicistronic RNAs, with all or part of the 5'UTR in the intercistronic space, were translated in rabbit reticulocyte lysates. In the presence of an upstream cistron, the chloramphenicol acetyltransferase gene, designed to block ribosomal scanning, the CVB3 5'UTR was capable of directing the internal initiation of translation of the downstream reporter gene (P1), confirming the presence of an internal ribosomal entry site (IRES). This finding was further supported by the data on predicted secondary structures within the 5'UTR. Of special note, analysis of various deletion mutants demonstrated that the IRES of CVB3 is located roughly at stem-loops G, H, and I spanning nucleotides (nt) 529 and 630. The region from nt 1 to 63 (stem-loop A) also appears important, and it may be an essential binding site for translation initiation factors. Based on these findings, in vitro translation inhibition assays using RNA fragments of the 5'UTR as inhibitor were performed. Both antisense and sense RNA segments transcribed from these two cis-acting regions and the surrounding sequence of the initiation codon AUG showed strong inhibition of viral protein synthesis. Antisense molecules may inhibit translation by blocking ribosome and initiation factor binding within the 5'UTR via specific hybridization to their viral RNA target sequences, while sense sequences may function by competing with viral RNA for ribosomes and/or translation initiation factors. These cis-acting translational elements may serve as potential targets for the antiviral action of oligomers.
Animals↗
Contractile responses of cultured bovine retinal pericytes to angiotensin II.
OBJECTIVE: To document that angiotensin (ANG) II contracts cultured bovine retinal pericytes via saralasin-sensitive receptors if the cells are prerelaxed. METHODS: Changes in the contractile tone were quantified as the changes in the summed length of wrinkles induced by pericytes cultured on the silicone surface. RESULTS: Angiotensin II (10(-5) mol/L) did not increase the contractile tone of cultured pericytes that were not prerelaxed. However, when the pericytes had been prerelaxed 41% with 10(-6)-mol/L sodium nitroprusside, ANG II at the range of 10(-7) to 10(-5) mol/L caused prompt, dose-related, significant (P<.01) contraction. It induced a maximum contraction (29.9%+/-5.2% [mean+/-SE]) at 10(-6) mol/L. This effect lasted at least 10 minutes. Angiotensin II receptor antagonist saralasin (10(-6) mol/L) abolished the contractile effect of ANG II (10(-6) mol/L), although by itself it did not affect the contractile tone. CONCLUSIONS: Angiotensin II contracts cultured pericytes through saralasin-sensitive ANG II receptors. If ANG II affects the contractile tone of pericytes in vivo, it may affect capillary caliber, resistance, and blood flow.
Angiotensin I↗
Factors associated with intraocular pressure-induced acute visual field depression.
OBJECTIVE: To determine the factors associated with visual field depression produced by artificial elevation of intraocular pressure (IOP). METHODS: The visual threshold was determined at 26 locations in the central visual field at a spontaneous IOP, at 30 mm Hg, at 40 mm Hg, and at the IOP immediately following release of the suction cup used to elevate the IOP artificially in 33 subjects with and without glaucoma. The net decrease in threshold sensitivity at each IOP level relative to sensitivity obtained at the spontaneous IOP was calculated (acute visual field depression). RESULTS: Factors potentially influencing the acute visual field depression between subjects were determined with stepwise regression. The reciprocal of ocular perfusion pressure, a clinical measure, was strongly correlated with acute visual field depression (dependent variable), particularly at 40 mm Hg (at 30 mm Hg, r=0.412, P=.02, n=32; and at 40 mm Hg, r=0.813, P<.001, n=33). When a second variable, the diagnosis of glaucoma, was included in the regression at 40 mm Hg, it contributed significantly (partial r=0.650, P<.001, n=26). The degree of glaucomatous damage (vertical cup-disc ratio or baseline Humphrey 24-2 visual field mean deviation) failed to correlate with acute field depression, with or without correction for ocular perfusion pressure. CONCLUSIONS: The elevation of IOP produces acute, reversible visual field depression. This depression is largely dependent on the subject's ocular perfusion pressure. The degree of depression is greater in those with glaucoma but is not strictly related to the degree of glaucomatous damage.
Acute Disease↗
Autoregulation of human optic nerve head circulation in response to increased intraocular pressure.
The following experiments were undertaken to determine if blood flow is maintained by autoregulation in the human optic nerve head when circulation is challenged by elevated intraocular pressure, and to determine if the presence or absence of autoregulation is universal. Laser Doppler flowmetry was used to determine the average velocity, the number of moving erythrocytes, and the volume of flow in the capillary bed of the optic disc. These parameters were measured in 10 subjects at spontaneous levels of intraocular pressure (IOP), and at pressures artificially elevated to 25, 35, 45 and 55 mm Hg with a scleral suction cup. Four subjects (two who showed autoregulation and two who did not) were studied on six additional occasions to determine consistency of the findings. In these same four subjects a second location on the disc was also measured on six occasions to determine if the IOP-effect on blood flow varied by location. Of the 10 subjects initially studied, seven maintained the baseline level of blood flow over the lower part of the range of elevated intraocular pressure (evidence of autoregulation), but showed a decline in flow by the time IOP reached 45 or 55 mm Hg. Two subjects showed a linear decline in blood flow beginning with the smallest increment of elevation of IOP (no autoregulation), and one showed an uninterpretable result. The two individuals who showed the linear decline and two of those who showed efficient autoregulation were remeasured, and each showed consistently the same pattern as before when restudied on six different occasions each. However, at a different location on their discs, autoregulation was manifest in all of these four individuals. When challenged by elevated IOP, the optic nerve head typically maintains a steady-blood flow over a range of IOP, but fails to maintain the same flow by the time IOP reaches 45 or 55 mm Hg. Some disc locations, at least in some individuals, do not show this autoregulation, but exhibit a decline in blood flow linearly related to IOP, even with the modest elevation of IOP.
Adult↗
Effect of oxygen on relaxation of retinal pericytes by sodium nitroprusside.
BACKGROUND: This study addresses whether oxygen modulates the relaxation induced in retinal pericytes by sodium nitroprusside (SNP), a nitric oxide (NO) donor that stimulates the NO/guanylate cyclase pathway. METHODS: Bovine retinal pericytes were cultured on silicone. On the silicone surface, basal pericyte contractile tone induces wrinkles. Drug-induced changes in pericyte contractile tone were assessed by changes in the number of wrinkles. The effects of 100% nitrogen (hypoxia) and 100% oxygen (hyperoxia) were studied on: (a) the basal tone of quiescent pericytes, (b) the relaxation to 3 and 10 microM SNP or 1 microM forskolin, and (c) the recontraction that followed the washout of 3 microM SNP or 1 microM forskolin. RESULTS: Neither hypoxia nor hyperoxia had any apparent influence on pericyte basal tone, on forskolin-induced relaxation, or on pericyte recontraction after a forskolin-induced relaxation. In hypoxia, relaxations to SNP 3 microM (P < 0.05) and 10 microM (P < 0.01) were significantly more pronounced than in hyperoxia. Hypoxia also reduced the recontraction after an SNP-induced relaxation (P < 0.001). CONCLUSION: Oxygen modulates the relaxation of bovine retinal pericytes evoked by SNP (guanylate cyclase-mediated), but not the relaxation induced by forskolin (adenylate cyclase-mediated). These results suggest that in the retinal capillary circulation an interaction between oxygen and the NO/guanylate cyclase pathway modulates pericyte tone, and thus potentially blood flow.
Animals↗
Targeted anti-cancer therapy using rituximab, a chimaeric anti-CD20 antibody (IDEC-C2B8) in the treatment of non-Hodgkin's B-cell lymphoma.
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Antibodies, Monoclonal↗
Myocarditis as systemic disease: new perspectives on pathogenesis.
1. Myocarditis may be an early indicator of or may subsequently lead to dilated cardiomyopathy in humans. This hypothesis has evolved from research on viruses that induce myocarditis, wherein the coxsackie B group viruses (CVB) in the family Picornaviridae are the most common known viral infectants of heart muscle. 2. Many competing hypotheses exist as to the pathogenesis of CVB3-induced myocarditis, including direct virus-induced myocyte damage and immunopathological disease with autoimmune sequelae. Evidence to support the direct-damage and viral RNA-persistence hypothesis is derived from in situ hybridization and gene amplification studies. 3. Recent use of terminal deoxynucleotidyl transferase-mediated nick-end labelling indicates that this injury in target organs is largely non-apoptotic in nature. Most apoptotic bodies in cardiac tissue are derived from immune cells. 4. Beyond infection of heart muscle, CVB3 can also associate with, infect and persist in cells of immune origin. The CVB3 localizes to follicles in spleens and lymph nodes of the murine host and this particular localization may continue in mice susceptible to more aggressive myocarditis. Whether virus-immune cell association in these compartments is advantageous (or essential) to the host in the evolution of anti-viral immune responses or whether it is more advantageous to the virus in immunosuppression of the host is not known. 5. We suggest that CVB3 can directly perturb or alter the immune response, thereby delaying viral clearance from vulnerable systemic organs. Both host and viral genetic factors can influence susceptibility, persistence and disease progression. 6. Picornaviruses use a unique method for the initiation of translation, involving the internal binding of the ribosome on a sequence element of the 5' untranslated region, termed an internal ribosome entry site (IRES). 7. The IRES of CVB3 is located at approximately stem loops G, H and I, spanning nucloetides 530 and 630. Arrest of host translation is also a feature of picornavirus infection. Such regulation of host cell translation machinery no doubt fosters viral replication at the expense of the host cell. 8. Differences between cell types in the mechanisms, along with those at other key steps in the viral life cycle and in signalling via kinase pathways, may determine viral tropism and cellular destruction and the physiological outcome of neighbouring cells.
Animals↗
Complement component 3 interactions with coxsackievirus B3 capsid proteins: innate immunity and the rapid formation of splenic antiviral germinal centers.
Innate immunity is central to the clearance of pathogens from hosts as well as to the definition of acquired immune responses (D. T. Fearon, and R. M. Locksley, Science 272:50-53, 1996). Coxsackievirus B3 (CVB3), a human cardiopathic virus, was evaluated for the ability to activate the alternative and classical pathway of complement. CVB3 proteins interact with complement component 3 (C3, a soluble protein effector of innate immunity) after either in vitro exposure to mouse serum or in vivo murine infection and activate the alternative pathway of complement. In addition, we demonstrate that viral antigen retention and localization in germinal centers is dependent on C3, while virus antigen retention in extrafollicular regions in the spleen is not. In vivo depletion of native C3 abolished the rapid formation of virus-specific germinal centers (by day 3 post-CVB3 infection) in the absence of serum anti-CVB3 antibodies. These studies demonstrate that innate immune mechanisms, such as C3 interaction with CVB3, are essential for splenic antiviral germinal center formation in naive (antigen nonsensitized) mice resistant (C57BL/6J strain) and susceptible (A/J strain) to CVB3-induced myocarditis.
Animals↗
Cost effectiveness of the prevention and treatment of deep vein thrombosis and pulmonary embolism.
The purpose of this article is to review and critically appraise the cost-effectiveness analyses that have compared various modalities for the prevention and treatment of deep vein thrombosis (DVT) and pulmonary embolism. Studies were identified by MEDLINE search and review of bibliographies of retrieved articles. Original economic analyses for the prevention or treatment of venous thromboembolism published in the English language literature were included in the analysis. In addition to collecting clinical and economic data, the methodological quality of the studies was evaluated using predefined criteria. Separate analyses were performed for studies of the prevention, and of the treatment, of venous thromboembolism following general surgery and following total hip arthroplasty. Fourteen cost-effectiveness analyses involving thromboembolic prophylaxis following total hip arthroplasty and 7 following general surgery met the eligibility criteria for this analysis. Each of the total hip arthroplasty studies containing a 'no intervention arm' determined that effective forms of prophylaxis not only reduced the rates of venous thromboembolic complications, but were less costly than a strategy of not providing venous thromboembolic prophylaxis. Six of 7 studies found low-molecular-weight (LMW) heparin to be more effective, and 4 of 7 found it to be less costly, than either unfractionated heparin or warfarin for the prevention of venous thrombosis following total hip arthroplasty. Following general surgical procedures, 6 of 7 studies found prophylaxis to be both more effective and less costly than no prophylaxis. Two studies also concluded that LMW heparin was more effective and less costly than unfractionated heparin for the prevention of DVT after general surgery. In general, the studies included in this overview were of high methodological quality with 11 of 15 studies fulfilling 4 or more of the 6 criteria for sound cost-effectiveness analyses. Effective venous thromboembolic prophylaxis results in fewer complications and is less costly than no prophylaxis following general surgery and total hip arthroplasty. LMW heparin was reported to be more efficacious and cost effective than unfractionated heparin following general surgery, and unfractionated heparin and warfarin following total hip arthroplasty. However, these findings must be regarded with caution in view of recent clinical trials and a meta-analysis reporting that the efficacy of LMW heparin and unfractionated heparin are similar following general surgery, and the efficacy of LMW heparin and warfarin are similar following total hip arthroplasty. Conclusions about the most cost-effective treatment for DVT await the publication of cost analyses from clinical trials comparing outpatient subcutaneous LMW heparin with inpatient therapy with intravenous unfractionated heparin.
Arthroplasty↗
Antagonism of soman-induced convulsions by midazolam, diazepam and scopolamine.
The effects of midazolam (MDZ), diazepam (DZ) and scopolamine (SCP) therapies on soman-induced electrocorticogram (ECoG) and biceps femoris electromyogram (EMG) activities and brain lesions were assessed in male rats. Animals received pyridostigmine (26 micrograms/kg, im) 30 min before soman (87.1 micrograms/kg, im) followed by therapy consisting of atropine (1.5 mg/kg) admixed with 2-PAM (25 mg/kg, im) 1 min later; MDZ (0.5 mg/kg), DZ (1.77 mg/kg) or SCP (0.43 mg/kg) was administered im at 1 min after the onset of convulsions (CVs). Typically, within 5 min after soman the ECoG profile changed to a full-blown, spike-and-dome epileptiform (SDE) pattern followed by CVs and increased amplitude of EMG activity. Treatment with SCP restored ECoG and EMG profiles by 30 min. At 2 hr after exposure only 1 animal demonstrated a slight abnormality in ECoG activity which was normal at 24 hr. Similarly, DZ and MDZ restored EcoG and EMG profiles by 30 min; however, in contrast to SCP, 83% of the animals demonstrated reappearance of SDE 2 hrs after soman. SCP therapy also enabled rats to move about in their cages by 30 min post treatment. In contrast, DZ- and MDZ-treated rats remained incapacitated as late as 2 hr post-exposure. Animals were euthanized at 24 hr, and the extent of soman-induced brain lesions was determined by light microscopic analysis. When present, brain lesions were minimal in SCP-treated rats. The mean brain lesion scores across all experimental conditions ranked as follows: soman control > MDZ > DZ > or = SCP = saline control. These observations suggest that SCP may be highly effective in severe soman intoxication.
Animals↗
Effect of CO2 on intracellular pH and contraction of retinal capillary pericytes.
PURPOSE: To test the potential participation of pericytes in the regulation of capillary blood flow according to metabolic needs. METHODS: The authors measured the change in extracellular pH (pHo), intracellular pH (pHi), and contractile tone of cultured bovine retinal pericytes when the ambient carbon dioxide (CO2) level was changed. RESULTS: Raising the partial pressure of CO2 (PCO2) from 5% to 10% or 20% acidified the medium, decreased the pHi, and relaxed the pericytes. Lowering the PCO2 from 5% to 0% or 2% alkalized the medium, raised the pHi, and contracted the pericytes. The reactions of pericytes in both cases were dose dependent. When the pHo was kept at approximately 7.4 as the PCO2 was changed by adjusting the ratio of NaHCO3 and NaCl in the medium (or by using HEPES buffer when PCO2 was zero), both elevating and lowering the PCO2 caused intracellular acidification but did not change the contractile tone of the retinal pericytes significantly. CONCLUSIONS: The effect of CO2 on the pHi and the contractility of pericytes is mediated primarily by its influence on the pHo. Elevation of CO2 causes pericytes to relax, whereas dispersion of CO2 causes pericytes to contract under the condition that allows pHo to be affected by PCO2. Therefore, pericytes may contribute to the regulation of local blood flow by their response to the change in local metabolic conditions.
Animals↗
Suppression of CO2-induced relaxation of bovine retinal pericytes by angiotensin II.
PURPOSE: To determine whether angiotensin II (Ang II), a vasoconstrictive peptide, changes the relaxation effect of elevated partial pressure of carbon dioxide (PCO2) on pericytes. METHODS: The contractile tone of cultured bovine retinal pericytes was measured when the ambient PCO2 was elevated in the absence or the presence of Ang II. All experiments were performed in the bicarbonate-buffered solution at 37 degrees C. RESULTS: Ang II (10(-6) M) by itself did not increase the baseline tone of the pericytes. Raising the PCO2 from 5% to 20% acidified the solution (pH dropped 0.51 +/- 0.02 U) and caused a sustained and statistically significant 22.9% +/- 4.6% relaxation of pericytes within 5 minutes (n = 8). In the presence of Ang II (10(-6) M), the maximum relaxation induced by 20% PCO2 was only 12.6% +/- 4.5% (n = 6) at 3 minutes, and the relaxation was not sustained. The effect of Ang II was statistically significant. Pretreatment with the competitive Ang II receptor antagonist saralasin (10(-6) M) for 10 minutes completely abolished the effect of Ang II (10(-6) M) on the response of pericytes to 20% PCO2. Saralasin by itself had no effect. CONCLUSIONS: Ang II attenuated the relaxing response of pericytes to elevated PCO2 through saralasin-sensitive Ang II receptors. Results suggest that some vasoactive agents, such as Ang II, could affect the pericyte responses to metabolic needs as signaled by local PCO2. This experimental design may permit further investigation of the altered physiology of local blood flow regulation.
Angiotensin II↗