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Laboratory Parameters (laboratory + parameter)
Selected AbstractsIntravenous Levetiracetam as first-line treatment of status epilepticus in the elderlyACTA NEUROLOGICA SCANDINAVICA, Issue 6 2010J. Fattouch Fattouch J, Di Bonaventura C, Casciato S, Bonini F, Petrucci S, Lapenta L, Manfredi M, Prencipe M, Giallonardo AT. Intravenous Levtiracetam as first-line treatment of status epilepticus in the elderly. Acta Neurol Scand: 2010: 121: 418,421. © 2010 John Wiley & Sons A/S. Background,,, Status epilepticus is a condition of prolonged/repetitive seizures that often occurs in the elderly. Treatment in the elderly can be complicated by serious side effects associated with traditional drugs. Objective,,, The aim of this pilot study was to evaluate the short-term efficacy/safety of intravenously administered LEV (IVLEV) as the treatment of choice for SE in the elderly. Methods,,, We enrolled nine elderly patients (five female/four male; median age 78 years) with SE. Two patients had a previous diagnosis of epilepsy; in the remaining seven, SE was symptomatic. SE was convulsive in five and non-convulsive in four. All the patients presented concomitant medical conditions (arrhythmias/respiratory distress/hepatic diseases). As the traditional therapy for SE was considered unsafe, IVLEV was used as first-line therapy (loading dose of 1500 mg/100 ml/15 min, mean maintenance daily dose of 2500 mg/24 h) administered during video-EEG monitoring. Results/conclusions,,, In all the patients but one, IVLEV was effective in the treatment of SE and determined either the disappearance of (7/8), or significant reduction in (1/8), epileptic activity; no patient relapsed in the subsequent 24 h. No adverse events or changes in the ECG/laboratory parameters were observed. These data suggest that IVLEV may be an effective/safe treatment for SE in the elderly. [source] Endothelial dysfunction in Buerger's disease and its relation to markers of inflammationEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 6 2006M. Joras Abstract Background, Buerger's disease (BD) is a segmental occlusive vascular disease. The aim of this study was to detect functional changes in brachial artery and asymptomatic morphological changes in extra-cranial carotid arteries not affected by the disease process and to assess markers of inflammation and endothelial damage. Materials and methods, Fourteen patients in the remission phase of BD and the same number of age- and sex-matched healthy controls were included in the study. The capability of endothelium-dependent (flow-mediated) and endothelium-independent dilation of the brachial artery and intima-media thickness of the carotid arteries were measured using high-resolution ultrasound. Laboratory parameters of endogenous fibrinolytic activity, inflammation and endothelial dysfunction were also measured. Results, Patients with BD had a diminished capability of endothelium-dependent vasodilation and higher levels of some circulating markers of inflammation, such as leukocytes, C-reactive protein, intercellular adhesion molecule-1 and E-selectin. Intercellular adhesion molecule-1 levels were related to some of the inflammatory markers (sedimentation rate, C-reactive protein, ,2-globulins and fibrinogen), while E-selectin was correlated with decreased endogenous blood fibrinolytic activity. Endothelium-dependent vasodilation was in negative correlation with the relative share of neutrophil granulocytes. There were no significant differences in intima-media thickness between patients with BD and controls. Conclusions, Our study has expressed generalized functional arterial disorder in patients with BD not accompanied by any measurable morphological changes of the carotid arterial wall. Functional deterioration of brachial artery could be related to increased levels of various inflammatory markers , the process which is most probably the basic pathogenetic mechanism of the disease. [source] The prevalence of lipodystrophy in an ambulant HIV-infected population: it all depends on the definitionHIV MEDICINE, Issue 3 2001VM Carter Objectives This study's objective was to determine the prevalence of body shape changes and metabolic abnormalities in an ambulant population with HIV infection. Three different definitions of lipodystrophy were used to assess these changes. Patients' anthropometric measures and dual-energy X-ray absorptiometry (DEXA) scans were compared in order to estimate fat distribution in this population. We sought to evaluate potential predictors for lipodystrophy according to each of the three definitions. Methods We performed a cross-sectional study in the outpatient clinic of a tertiary referral hospital in Melbourne, Australia. We enrolled a total of 167 HIV-infected ambulatory patients over 3 months in mid-1998. Data on 159 males, 149 of whom were receiving triple combination antiretroviral therapy, were evaluated. Anthropometric measures, clinical examination, self-report of body shape changes, biochemical measures and DEXA scan were used to assess lipodystrophy and risk factors for cardiovascular disease. Patients described body shape changes in the face, trunk, arms and legs. Laboratory parameters measured included fasting triglyceride (TG), cholesterol, high-density lipoproteins (HDL), glucose, insulin, CD4 cell count and plasma HIV RNA. Current and past antiretroviral therapies were ascertained. Results According to one proposed Australian national definition of lipodystrophy (LDNC), the prevalence of lipodystrophy in this population was 65%. This definition included an objective assessment with major and minor criteria. Patient-defined lipodystrophy (LDP), which involved a subjective assessment of thinning arms and legs and central adiposity, occurred in 19%. Patient-defined lipoatrophy (LAP), which involved a subjective assessment of thinning arms and legs without central adiposity, occurred in 21.3%. No change in body habitus was noted by 37% of the cohort. Hypercholesterolaemia was recorded in 44%, hypertriglyceridaemia in 52% and elevated insulin levels in 23%. Anthropometry was predictive of the per cent total body fat recorded by DEXA scan, but produced consistently lower values. In multivariate analysis, LDP and LAP were significantly associated with stavudine (d4T) use, while LAP was also associated with zidovudine (ZDV) treatment. There were no treatment associations with LDNC. Protease inhibitor (PI) exposure was associated with metabolic changes but not patient perceived body shape changes, while d4T and ZDV exposure was associated with increased triglycerides and reduced peripheral fat stores. Conclusions The prevalence of body shape changes in a single population varied depending on the definition applied. The LDNC definition overestimated body shape abnormalities in comparison with patient perception. LAP was associated with significantly lower fat stores measured by anthropometry and DEXA scan than those identified under the LDNC definition. In contrast to LDNC, LAP was associated with d4T exposure, nucleoside reverse transcriptase inhibitor (NRTI) and ZDV duration of use, but not PI use. Until a consensus definition for lipodystrophy is developed, including agreement on objective measurement and thresholds for abnormality, careful description of the individual components of the syndrome is required to enable cohort comparisons so that predictors of the syndrome can be assessed more accurately and outcome studies made feasible. [source] Oral findings in three different groups of immunocompromised patientsJOURNAL OF ORAL PATHOLOGY & MEDICINE, Issue 4 2000Ulrich Meyer Abstract: The objective of this study was to determine the frequency of oral, dental and periodontal findings in three different groups of immunocompromised patients and in a healthy control group, to evaluate whether there is a correlation between manifestations of disease and immunologic parameters. The survey included 46 patients with a diagnosis of systemic lupus erythematosus, 48 heart transplant recipients, and 53 adult patients suffering from acute leukemias. Fifty matched healthy subjects were used as a control group. Each patient had to answer questions on medical and dental health and underwent a thorough oral, dental and serological investigation. Oral mucosal lesions were found in nearly half of all immunocompromised patients (49.6%), but in only 26% of control patients. No significant associations were found between different types of oral lesions and the underlying cause of immunosuppression. Leukemia patients showed age-unrelated higher scores in periodontal indices (P<0.05). Laboratory parameters failed to be significant in the assessment of oral health. [source] Topical paricalcitol (19-nor-1,,25-dihydroxyvitamin D2) is a novel, safe and effective treatment for plaque psoriasis: a pilot studyBRITISH JOURNAL OF DERMATOLOGY, Issue 1 2004C. Durakovic Summary Background, There continues to be a need to develop new pharmacological approaches for treating psoriasis. Topical active vitamin D compounds have proven to be both safe and effective for treating psoriasis. Paricalcitol (19-nor-1,,25-dihydroxyvitamin D2) is a novel vitamin D analogue which has been developed for the prevention of secondary hyperparathyroidism in patients with chronic renal failure. Objectives, To investigate the efficacy and safety of 12 weeks' therapy with a once-daily application of paricalcitol ointment (15 ,g g,1) in comparison with placebo ointment. Methods, This pilot double-blinded self-controlled study was initiated in 11 patients with moderate plaque psoriasis. To characterize the biological effects further and to evaluate the efficacy of topical paricalcitol treatment in psoriasis, we have analysed immunohistochemically the expression of one of the markers for epidermal differentiation (transglutaminase K) in paricalcitol-treated skin as compared with placebo treatment. Results, Treatment with paricalcitol was superior to placebo treatment beginning at week 1. The global severity score for erythema, plaque elevation and scaling was improved significantly more by paricalcitol ointment than by placebo (P < 0·001). Similar results were obtained for assessments of scaling, erythema and plaque elevation. No symptoms of local skin irritation were noted. Laboratory parameters including serum calcium, phosphorus, parathyroid hormone and urinary calcium/creatinine ratio did not reveal any changes of clinical relevance during treatment. The immunoreactivity of transglutaminase K changed after 12 weeks of paricalcitol treatment almost completely to the pattern characteristic for nonlesional psoriatic skin. Conclusions, Once-daily application of paricalcitol ointment was safe and effective for the treatment of plaque psoriasis. [source] Adaptation and evaluation of the Randox full-range CRP assay on the Olympus AU2700®JOURNAL OF CLINICAL LABORATORY ANALYSIS, Issue 1 2007A.M. Dupuy Abstract The implementation of a high-sensitivity CRP (hs-CRP) assay as a routine laboratory parameter may be necessary. A single CRP method that could yield reliable results for the whole concentration range (0.1,200 mg/L) would be the most practical solution for the laboratory setting. The aim of this study was to assess the Randox full-range CRP assay on the Olympus AU2700® biochemistry analyzer and evaluate its analytical performance on serum and heparin plasma samples. The Randox CRP turbidimetric assay was compared with the existing CRP assay used routinely on the Olympus AU2700®. The analytical performance of the Randox CRP with both Olympus CRP reagents (CRP for normal application andhs-CRP) was good. We found that the Randox CRP method in the range of 0.5,160 mg/L was closely correlated to the Olympus CRP and hs-CRP for serum samples. According to a Bland-Altman analysis, the serum and heparinized samples showed an excellent agreement in CRP concentrations throughout the entire range (mean difference = ,0.035 ± 1.806 mg/L) as well as in CRP levels <10 mg/L. Our data indicate that Randox full-range CRP measurements using an immunoturbidimetry assay on Olympus systems perform as well for routine diagnostics as other high-sensitivity applications using serum or heparin plasma. J. Clin. Lab. Anal. 21:34,39, 2007. © 2007 Wiley-Liss, Inc. [source] Serum osmolality and outcome in intensive care unit patientsACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 8 2006B. Holtfreter Background:, The aim of the present study was to compare 16 routine clinical and laboratory parameters, acute physiologic and chronic health evaluation (APACHE) and sequential organ failure assessment (SOFA) score for their value in predicting mortality during hospital stay in patients admitted to a general intensive care unit (ICU). Methods:, A retrospective observational clinical study was carried out in a 15-bed ICU in a university hospital. Nine hundred and thirty-three consecutive patients with ICU stay > 24 h (36.2% surgical, 29.1% medical and 34.7% trauma) were observed. Blood sampling, patient surveillance and data collection were performed. The primary outcome was mortality in the hospital. We used receiver operating characteristic (ROC) analyses and logistic regression to compare the 16 relevant parameters, APACHE II and SOFA scores. Results:, Two hundred and thirty-three out of the 933 patients died (mortality 25.0%). One laboratory parameter, serum osmolality [area under the curve (AUC) 0.732] had a predictive value for mortality which lay between that of APACHE II (AUC 0.784) and SOFA (AUC 0.720) scores. When outcome prediction was restricted to long-term patients (ICU stay > 5 days), serum osmolality (AUC 0.711) performed better than either of the standard scores (APACHE AUC 0.655, SOFA AUC 0.636). Using logistic regression analysis, the association of clinical parameters, age and diagnosis group with mortality was determined. Conclusion:, Elevated serum osmolality at ICU admission is associated with an increased mortality risk in critically ill patients. Serum osmolality is cheaper and more rapid to determine than the scoring systems. However, further studies are needed to evaluate the predictive value of serum osmolality in different patient populations. [source] Immature platelet fraction as novel laboratory parameter predicting the course of neonatal thrombocytopeniaBRITISH JOURNAL OF HAEMATOLOGY, Issue 4 2009Malte Cremer No abstract is available for this article. [source] Spontaneous apoptosis in chronic lymphocytic leukemia and its relationship to clinical and cell kinetic parametersCYTOMETRY, Issue 6 2001Gislaine B. Oliveira Abstract Chronic lymphocytic leukemia (CLL) presents considerable variability in clinical presentation as well as in its evolution. In contrast to the inhibition of apoptosis in vivo, spontaneous apoptosis after short-term culture occurs. We studied the degree of this apoptosis in vitro, and its interactions with several clinical and laboratory parameters. Apoptosis was measured by the annexin V technique. Proliferation rate was evaluated by the AgNOR (nucleolar organizer regions) technique. There were inverse correlations between the percentage of annexin V-positive cells and peripheral lymphocyte count (r = - 0.49), Rai stage (r = - 0.40), Binet stage (r = - 0.50), TTM (total tumor mass score; r = - 0.51), and percentage of cells with one AgNOR cluster (r = - 0.45). Direct correlations were found with hemoglobin values ( r = 0.34) and platelet counts (r = 0.52). The number of CD8-positive cells showed a correlation with peripheral lymphocyte count (r = 0.49). When this variable was held constant, a correlation was detected between CD8-positive cells and staging (r = -0.47), TTM (r = - 0.42), and platelet count (r = 0.67). CD4-positive lymphocytes presented a correlation only with CD8-positive lymphocytes. In a cluster analysis, it was possible to create three groups of patients with different apoptosis rates using the TTM and AgNOR values. We conclude that, with the progression of the disease, together with the increase of tumor mass and proliferation rate, there is a decrease in the suceptibility to apoptosis. Cytometry (Comm. Clin. Cytometry) 46:329,335, 2001. © 2001 Wiley-Liss, Inc. [source] THE MOLECULAR FUTURE IN CYTOLOGYCYTOPATHOLOGY, Issue 2006M. Salto-Tellez Molecular diagnosis is the application of molecular biology techniques and knowledge of the molecular mechanisms of disease to diagnosis, prognostication and treatment of diseases. Molecular Diagnosis is, arguably, the fastest growing area of diagnostic medicine. The US market for molecular testing generated $1.3 billion in 2000, which was predicted to increase to about $4.2 billion by 2007.1 We proposed the term Diagnostic Molecular Cytopathology to define the application of molecular diagnosis to cytopathology2. Diagnostic Molecular Cytopathology is essential for the following reasons: (i) Molecular testing is sometimes indispensable to establish an unequivocal diagnosis on cell preparations; (ii) Molecular testing provides extra information on the prognosis or therapy of diseases diagnosed by conventional cytology; (iii) Molecular testing provides genetic information on the inherited nature of diseases that can be directly investigated in cytology samples, by either exfoliation or by fine needle aspiration; (iv) Sometimes the cytopathology sample is the most convenient (or the only available) source of material for molecular testing; (v). Direct molecular interrogation of cells allows for a diagnostic correlation that would otherwise not be possible. Parallel to this direct diagnostic implication, cytopathology is increasing important in the validation of biomarkers for specific diseases, and in therefore of significant importance in the overall translational research strategies. We illustrate its application in some of the main areas of oncology molecular testing, such as molecular fingerprinting of neoplasms,3 lymphoreticular diseases,2 sarcomas4 and lung cancer,5 as well as translational research using diagnostic cytopathology techniques. The next years will see the consolidation of Diagnostic Molecular Cytopathology, a process that will lead to a change of many paradigms. In general, diagnostic pathology departments will have to reorganize molecular testing to pursue a cost-efficient operation. Sample preparation will have to take into account optimal preservation of nuclear acids. The training of technical staff and the level of laboratory quality control and quality assurance would have to follow strict clinical (not research) laboratory parameters. And, most importantly, those pathologists undertaking molecular diagnosis as a discipline would have to develop their professional expertise within the same framework of fellowships and professional credentials that is offered in other sub-specialties. The price to pay if this effort is not undertaken is too important for the future of diagnostic pathology in general. The increasing characterization of molecular biomarkers with diagnostic, prognostic or therapeutic value is making the analysis of tissue and cell samples prior to treatment a more complex exercise. If cytopathologists and histopathologists allow others to take charge of molecular diagnosis, our overall contribution to the diagnostic process will be diminished. We may not become less important, but we may become less relevant. However, those within the discipline of diagnostic pathology who can combine the clinical background of diseases with the morphological, immunocytochemical and molecular diagnostic interpretation will represent bona fide diagnostic specialists. Such ,molecular cytopathologists' would place themselves at the centre of clinical decision-making. Reference:, 1. Liz Fletcher. Roche leads molecular diagnostics charge. Nature Biotechnol 20, 6,7; 2002 2. Salto-Tellez M and Koay ESC. Molecular Diagnostic Cytopathology - Definitions, Scope and Clinical Utility. Cytopathology 2004; 15:252,255 3. Salto-Tellez M, Zhang D, Chiu LL, Wang SC, Nilsson B, and Koay ESC. Immunocytochemistry Versus Molecular Fingerprinting of Metastases. Cytopathology, 2003 Aug; 14(4):186,90. 4. Chiu LL, Koay SCE, Chan NL and Salto-Tellez M. Molecular Cytopathology: Sequencing of the EWS-WT1 Gene Fusion Transcript in the Peritoneal Effusion of a Patient with Desmoplastic Small Round Cell Tumour. Diagnostic Cytopathology, 2003 Dec; 29(6): 341,3. 5. TM Chin, D Anuar, R Soo, M Salto-Tellez, WQ Li, B Ahmad, SC Lee, BC Goh, K Kawakami, A Segal, B Iacopetta, R Soong. Sensitive and Cost-Effective deptection of epidermal growth factor Receptor Mutations in Small Biopsies by denaturing High Performance Liquid Chromatography. (In press). [source] Enhanced Left Ventricular Endocardial Border Delineation with an Intravenous Injection of SonoVue, a New Echocardiography Contrast Agent:ECHOCARDIOGRAPHY, Issue 8 2000A European Multicenter Study The safety and efficacy of SonoVue (also referred to as BR1), a new contrast agent for delineating endocardial border of the left ventricle after intravenous administration, was assessed. Two hundred and eighteen patients with suspected coronary artery disease undergoing fundamental echocardiography for the assessment of left ventricle were enrolled in a prospective multicenter, single blind, cross-over study with random sequence allocation of four different doses of SonoVue. Endocardial border definition in the apical and parasternal views was scored as O = not visible, 1 = barely visible, and 2 = well visualized before and after contrast enhancement. Analysis was performed by two pairs of off-site observers. Safety of SonoVue was also assessed. Results of our study indicated that the mean improvements in the endocardial border visualization score were as follows: 3.1 ± 7.8 (95% CI, 2.5 and 3.7) for 0.5 ml, 3.4 ± 8.0 (95% CI, 2.8 and 4.0) for 1 ml, 3.4 ± 7.9 (95% CI, 2.8 and 4.0) for 2 ml, and 3.7 ± 8.0 (95% CI, 3.1 and 4.3) for 4 ml (P < 0.05 for all doses from baseline). Changes from baseline in endocardial visualization scores were also seen in the apical views (P < 0.05) and they were dose-dependent (P < 0.001). Similar enhancements of endocardial visualization scores were observed in the apical views in patients with suboptimal baseline echocardiographic images. Diagnostic confidence for assigning a score and image quality also were significantly better following contrast enhancement. No significant changes in the laboratory parameters and vital signs were noted following contrast enhancement, and the side effects were minimal. It was concluded that SonoVue is safe and effective in delineating endocardial border, including in patients with suboptimal baseline images. [source] Severe hypertriglyceridaemia in clinically ill horses: diagnosis, treatment and outcomeEQUINE VETERINARY JOURNAL, Issue 6 2003B. DUNKEL Summary Reasons for performing study: Sporadic measurement of serum triglycerides in depressed and inappetant clinically ill horses revealed severe hypertriglyceridaemia without visible evidence of lipaemia on several occasions, leading to the inclusion of serum triglyceride concentrations in the routine serum biochemistry evaluation of our hospital. Since then, more cases have been identified and treated for hypertriglyceridaemia, raising questions about the prevalence, predisposing factors and significance of these findings. Hypotheses: 1) Severe hypertriglyceridaemia without visible opacity of the serum occurs more commonly in clinically ill and inappetant horses than previously described and 2) appropriate treatment using i.v. dextrose and/or partial parenteral nutrition would decrease serum triglycerides to normal limits and might result in improved appetite and attitude of the patient. Methods: The laboratory computer database from 2000 and 2001 was searched for increased serum triglycerides (>5.65 mmol/l) in any horse breed, ponies and miniature breeds excluded. Data analysed included subject details, diagnosis, clinical and laboratory parameters, treatment, response to treatment and outcome. Results: Severe hypertriglyceridaemia was identified in 13 horses, with serum triglyceride concentrations 6.17,18.29 mmol/l, while none showed visible lipaemia. All horses had clinical and laboratory findings consistent with systemic inflammatory response syndrome and all but one had an increased serum creatinine concentration. Treatment with i.v. dextrose and/or partial parenteral nutrition resulted in decrease of the serum triglycerides to normal limits. Conclusions: Severe hypertriglyceridaemia occurs in inappetant and clinically ill horses without evidence of serum opacity more commonly than previously described. The presence of systemic inflammatory response syndrome might predispose horses to hypertriglyceridaemia, while the increased creatinine concentration might be a predisposing factor or result of the condition. Horses identified in our study readily responded to treatment and appetite and attitude improved coincident with decrease of the serum triglycerides to normal limits. Potential relevance: Hypertriglyceridaemia could perpetuate inappetance and depression in clinically ill horses and potentially predispose to fatty infiltration of the liver and other organ systems. [source] CLINICAL STUDY: Effect of saquinavir/ritonavir (1000/100 mg bid) on the pharmacokinetics of methadone in opiate-dependent HIV-negative patients on stable methadone maintenance therapyADDICTION BIOLOGY, Issue 3 2009Candice Jamois ABSTRACT This study was performed to determine the effect of two protease inhibitors, saquinavir (SQV, oral 1000 mg bid) boosted by ritonavir (RTV, oral 100 mg bid), on pharmacokinetics (PK) of methadone in opiate-dependent HIV-negative patients on stable methadone maintenance therapy. This was a two-center, open-label, one-sequence cross-over, multiple-dose study in 13 HIV-negative patients who were on stable methadone therapy (oral, 60,120 mg qd). All patients continued methadone treatment on days 2,15. All patients received SQV/RTV in combination with methadone from days 2,15. PK of methadone was assessed on day 1 (alone) and on day 15 when methadone treatment was combined with SQV/RTV at steady state. Twelve patients completed the study. Median age, body weight and height were 50 years (range: 24,54 years), 80 kg (range: 57,97 kg) and 174 cm (range: 163,189 cm), respectively. All patients were Caucasian, and 11 were smokers. Median methadone dose was 85 mg qd. Geometric mean area under curve of the plasma concentration-time curve over 24 hour dosing interval (AUC0,24 hour) ratio of methadone with and without SQV/RTV was 0.81% (90% confidence interval: 71,91%). There was no significant plasma protein-binding displacement of methadone by SQV/RTV. The combination of SQV/RTV and methadone was well tolerated. There were no clinically significant adverse events or significant changes in laboratory parameters, electrocardiograms or vital signs. The 19% decrease in R-methadone AUC0,24 hour in the presence of SQV/RTV was not clinically relevant. There appears to be no need for methadone dose adjustment when methadone (60,120 mg qd) and SQV/RTV (1000/100 mg bid) are coadministered. [source] Is it possible to identify early predictors of the future cost of chronic arthritis?FUNDAMENTAL & CLINICAL PHARMACOLOGY, Issue 1 2009The VErA project Abstract This study was conducted to identify early predictors of the total cost of inflammatory arthritis (IA). One hundred and eighty patients affected by undifferentiated arthritis (UA) or rheumatoid arthritis (RA) were included in the French Very Early rheumatoid Arthritis (VErA) cohort between 1998 and 2001. Health economic data for 2003 were collected using a patient self-questionnaire. Results were analysed in terms of direct, indirect and total costs in 2003 euros (2003,) for the population as a whole and in diagnostic subgroups. A payor perspective (the French National Health Insurance, in this case) was adopted. Multiple linear regression models were used to identify predictors of total cost from among the criteria assessed on recruitment. Results of the study showed that for the study population as a whole, the mean total cost was ,4700 per patient. The costs attributable to the RA and UA sub-groups were ,5928 and ,2424 per patient, respectively. In a univariate analysis, certain parameters were significantly correlated with a higher cost of illness. In the multivariate analysis, some of these parameters were further identified as being predictive of higher cost. Two strong significant, early predictors of total cost were identified: higher pain (P = 0.002) and the presence of rheumatoid factor (P = 0.004). In the RA sub-group, lower grip strength of the dominant hand (P = 0.039) was another predictor of the illness's subsequent economic impact. In conclusion, our data show that simple clinical and laboratory parameters can be used early in the course of IA to predict the condition's impact on healthcare budgets. [source] A randomized, double-blind trial demonstrating bioequivalence of the current recombinant activated factor VII formulation and a new robust 25°C stable formulationHAEMOPHILIA, Issue 5 2007B. V. BYSTED Summary., Recombinant activated factor VIIa (rFVIIa) is a well-established treatment for bleeding episodes in patients with congenital or acquired haemophilia A or B with inhibitors to factors VIII and IX and patients with FVII deficiency. The aim of this trial was to demonstrate bioequivalence between the currently marketed (rFVIIa/NovoSeven®) and a new rFVIIa formulation (VII25) stable at up to 25°C. Furthermore, short-term safety and tolerability of VII25 and pharmacokinetics of both formulations were investigated. In this single-centre, randomized, double-blind, two-way cross-over trial, healthy male subjects received one intravenous bolus injection of rFVIIa and one of VII25, both at 90 ,g kg,1, in a randomized order 2,3 weeks apart. Mean VII25/rFVIIa ratio for area under the plasma activity-time curve from time 0 to last quantifiable activity (primary bioequivalence endpoint), was 0.93, 90% confidence interval (CI) (0.89,0.96), within the predefined bioequivalence range (0.80,1.25). Secondary pharmacokinetic parameters were comparable between formulations. No serious adverse events were observed. Six mild or moderate treatment-emergent adverse events were reported in five subjects. Coagulation-related parameter profiles were similar between rFVIIa and VII25. No clinically abnormal changes were observed for laboratory parameters and no subjects developed FVIIa antibodies. This trial demonstrated bioequivalence between the currently available rFVIIa and VII25 stable at up to 25°C. VII25's ,user-friendly' formulation removes the inconvenience of storing/transporting at 2,8°C, and as the drug substance is the same, the activity and safety established for rFVIIa is maintained. [source] Structured treatment interruption in patients with alveolar echinococcosisHEPATOLOGY, Issue 2 2004Stefan Reuter In human alveolar echinococcosis (AE), benzimidazoles are given throughout life because they are only parasitostatic. It has been a longstanding goal to limit treatment, and recent reports suggest that, in selected cases, benzimidazoles may be parasitocidal. Previously, we showed that positron ,emission tomography (PET) using [18F]fluoro-deoxyglucose discriminates active from inactive lesions in AE. We have now performed a 3-year prospective study in 23 patients and conducted a structured treatment interruption in those without signs of PET activity. Disease progression was further assessed by ultrasound, computerized tomography, laboratory parameters, and clinical examination. We found PET-negative lesions in 15 of 23 patients and benzimidazoles were discontinued in these patients. After 18 months, patients were reevaluated, and, of the 15 initially PET-negative patients, 8 showed either new activity on PET (n = 6) or signs of clinical progression (n = 2). Reinitiation of benzimidazoles halted parasite growth again. No further progression was detected after 36 months. PET had a sensitivity of 91% for the detection of active lesions. In conclusion, despite successful suppression of metabolic activity, in most cases benzimidazoles do not kill the parasite. PET is a reliable tool for assessing metabolic activity and for timely detection of relapses. Neither duration of treatment, kind of treatment, lesion size, calcifications, or regressive changes reliably indicate parasite death. We discourage the discontinuation of benzimidazoles in inoperable AE even after many years of treatment. However, patients with a poor compliance of benzimidazole intake or patients suffering from side effects to benzimidazoles might be assessed for PET negativity. If permanent discontinuation of benzimidazoles is attempted, the course of disease should be followed by PET. (HEPATOLOGY 2004;39:509,517.) [source] Should we give thromboprophylaxis to patients with liver cirrhosis and coagulopathy?HPB, Issue 6 2009Marco Senzolo Abstract Patients with liver cirrhosis are characterized by decreased synthesis of both pro- and anticoagulant factors, and recently there has been evidence of normal generation of thrombin resulting in a near normal haemostatic balance. Although it is generally recognized that bleeding is the most common clinical manifestation as a result of decreased platelet function and number, diminished clotting factors and excessive fibrinolysis, hypercoagulability may play an under recognized but important role in many aspects of chronic liver disease. In fact, they can encounter thrombotic complications such as portal vein thrombosis, occlusion of small intrahepatic vein branches and deep vein thrombosis (DVT). In particular, patients with cirrhosis appear to have a higher incidence of unprovoked DVT and pulmonary embolism (PE) compared with the general population. In dedicated studies, the incidence of DVT/PE ranges from 0.5% to 1.9%, similar to patients without comorbidities, but lower than patients with other chronic diseases (i.e, renal or heart disease). Surprisingly, standard coagulation laboratory parameters are not associated with a risk of developing DVT/PE; however, with multivariate analysis, serum albumin level was independently associated with the occurrence of thrombosis. Moreover, patients with chronic liver disease share the same risk factors as the general population for DVT/PE, and specifically, liver resection can unbalance the haemostatic equilibrium towards a hypercoagulable state. Current guidelines on antithrombotic prophylaxis do not specifically comment on the cirrhotic population as a result of the perceived risk of bleeding complications but the cirrhotic patient should not be considered as an auto-anticoagulated patient. Therefore, thromboprophylaxis should be recommended in patients with liver cirrhosis at least when exposed to high-risk conditions for thrombotic complications. Low molecular weight heparins (LWMHs) seem to be relatively safe in this group of patients; however, when important risk factors for bleeding are present, graduated compression stockings or intermittent pneumatic compression should be considered. [source] Fracture of the pancreas in two patients after a go-kart accidentHPB, Issue 1 2001M J Govaert Background After blunt abdominal trauma, an isolated injury to the pancreatic duct is uncommon. Physical signs and laboratory parameters are often inaccurate, and missing this diagnosis can cause serious clinical problems. Case outlines Two young women (aged 18 and 20 years) are reported who sustained isolated trauma to the pancreatic duct in go-kart accidents. Each patient sustained a fracture of the pancreas. This injury was diagnosed only after a period of clinical observation with repeated laboratory parameters, ultrasound and CT scan. Pancreatic tissue was conserved by performing a pancreaticojejunostomy. Discussion After any episode of blunt abdominal trauma, isolated injury to the pancreatic duct should be considered. Serum analysis, ultrasonography and CT scanning can be helpful in early diagnosis. Preservation of pancreatic tissue can be achieved with a good clinical outcome. [source] Systemic and local cytokine production in quiescent ulcerative colitis and its relationship to future relapse: A prospective pilot studyINFLAMMATORY BOWEL DISEASES, Issue 6 2005Takayuki Yamamoto MD Abstract Background: The main aim of this prospective study was to examine whether systemic (plasma) and local (mucosal) cytokine production is a predictor of future relapse in patients with quiescent ulcerative colitis (UC). The impact of other clinical and laboratory parameters on relapse was also studied. Methods: Fifty consecutive patients with quiescent UC were included. At enrollment, blood and mucosal (rectal biopsies) samples were collected. All patients were followed up regularly for 1 year after enrollment. Plasma and mucosal cytokine levels were measured by enzyme-linked immunosorbent assay. To identify independent significant predictive factors for relapse, time-dependent analyses using the Kaplan-Meier method and the Cox proportional hazard model were performed. Results: Thirty-four patients remained in remission, and 16 patients relapsed during the 1-year follow-up. Higher interleukin (IL)-8 levels in the rectal mucosa were significantly associated with relapse. In contrast, IL-1,, IL-6, and tumor necrosis factor-, levels in the rectal mucosa were not associated with relapse. Conventional blood markers and plasma cytokines (IL-1,, IL-6, IL-8, and tumor necrosis factor-,) did not correlate with relapse. Among clinical factors, age and number of prior relapses were significantly associated with relapse. In multivariate analysis, a higher rectal mucosal IL-8 level (,160 pg/mg of tissue; hazard ratio, 4.7), younger age (<30 yr; hazard ratio, 7.3), and a greater number of prior relapses (,5; hazard ratio, 4.3) were independent significant risk factors for future relapse. Conclusions: Rectal mucosal IL-8 measurement might be an additional objective diagnostic tool that can predict relapse in patients with quiescent UC. [source] Response of refractory colitis to intravenous or oral tacrolimus (FK506)INFLAMMATORY BOWEL DISEASES, Issue 5 2002Dr. Klaus Fellermann Abstract Intravenous cyclosporine has proven to be an alternative to emergency colectomy in steroid-refractory ulcerative colitis, whereas the experience with FK506 is limited. In this report we compare intravenous to oral FK506 treatment in 38 patients with refractory ulcerative (n = 33) or indeterminate (n = 5) colitis. FK506 was started intravenously in the first group (n = 18) at a dose of 0.01 to 0.02 mg/kg up to 14 days, followed by 0.1 to 0.2 mg/kg orally, or was started orally at this dose in a second group (n = 20). Additional azathioprine/6-mercaptopurine was given and steroids were tapered in responding patients, followed by a dose reduction of FK506. Clinical disease activity and laboratory parameters were assessed to evaluate efficacy and safety. Primary objectives were the induction of remission (Truelove index of mild) and colectomy-free survival. Treatment lasted for a mean of 7.6 months, and the mean observation period was 16.2 months. Eighteen of 38 patients improved within 14 days, and a complete remission was achieved in 13 patients after 1 month. A colectomy within 1 month was performed in 3 of 38 patients. The overall colectomy rate was 34%. One-half of the patients with a minimum follow-up of 2 years required a colectomy. Intravenous and per oral administration were equally safe and effective. The most frequent adverse events included tremor, hyperglycemia, hypertension, and infection, but none were severe. Renal impairment was rare and subsided upon drug withdrawal. In conclusion, FK506 is effective in the treatment of refractory colitis with per oral dosing being equivalent to intravenous administration. [source] Lupus erythematosus associated with erythema multiforme: Rowell's syndromeINTERNATIONAL JOURNAL OF DERMATOLOGY, Issue 2007Nadia H. Shadid MD About 45 years ago, the association of lupus erythematosus with erythema multiforme and specific immunological laboratory changes was described for the first time. Since then, several patients with similar constellations of clinical symptoms and laboratory parameters have been reported. Today, this disease is known as Rowell's syndrome. However, the fact that not all patients described previously fit all clinical and immunological characteristics that had been originally reported raised the question if Rowell's syndrome really is an own entity or if the simultaneous occurrence of these clinical and immunological signs is rather incidental. Here, we describe a patient fulfilling most of the criteria of Rowell's syndrome and discuss what is currently known about this rare condition. [source] Safety of efalizumab in adults with chronic moderate to severe plaque psoriasis: A phase IIIb, randomized, controlled trialINTERNATIONAL JOURNAL OF DERMATOLOGY, Issue 5 2006Kim A. Papp MD Background, To provide safety data for efalizumab, a recombinant humanized monoclonal IgG1 antibody, in adults with chronic plaque psoriasis. Methods, A 12-week, Phase IIIb, randomized, double-blind, parallel-group, placebo-controlled trial. At 58 study sites in the USA and Canada, 686 patients with moderate to severe chronic plaque psoriasis received an initial conditioning dose of efalizumab 0.7 mg/kg subcutaneously (SC) followed by either 11 weekly doses of efalizumab 1 mg/kg SC or matching placebo. Main outcome measures were safety and tolerability outcomes (primary) and efficacy outcomes (secondary). Results, During 12 weeks of therapy with efalizumab or placebo, the incidence of clinical adverse events was 82.2% and 72.9%, respectively; the incidence of serious adverse events was 1.8% and 3.4%, respectively; and the incidence of nonserious adverse events leading to withdrawal was 1.8% and 1.7%, respectively. In the efalizumab group, there were no clinically significant changes in vital signs or laboratory parameters and no evidence of end-organ toxicities. A significantly higher proportion of patients receiving efalizumab than those receiving placebo achieved , 75% improvement in the Psoriasis Area and Severity Index (PASI) (P < 0.001), , 50% improvement in PASI (P < 0.001), and a static Physician's Global Assessment rating of Minimal or Clear (P < 0.001). The mean improvement in the Psoriasis Symptom Assessment was significantly greater in the efalizumab group (P < 0.001). Conclusions, Efalizumab treatment SC for 12 weeks was safe, well tolerated, and effective in patients with moderate to severe chronic plaque psoriasis. [source] Once-daily desloratadine improves the signs and symptoms of chronic idiopathic urticaria: a randomized, double-blind, placebo-controlled studyINTERNATIONAL JOURNAL OF DERMATOLOGY, Issue 1 2001Johannes Ring MD Background Chronic idiopathic urticaria (CIU) is the most common type of chronic urticaria, and pruritus is the most prominent symptom. Antihistamines are the first-line treatment for CIU. Sedation and anticholinergic adverse effects are often experienced with the first-generation antihistamines and there is a risk of cardiovascular adverse effects and drug interactions with some second-generation agents. Hence, new treatment options are needed. Desloratadine is a new, potent, nonsedating antihistamine that has an excellent cardiovascular safety profile. Methods This was a multicenter, randomized, double-blind, placebo-controlled study designed to determine the efficacy and safety of desloratadine in the treatment of moderate-to-severe CIU. A total of 190 patients, aged 12,79 years, with at least a 6-week history of CIU and who were currently experiencing a flare of at least moderate severity, were randomly assigned to therapy with desloratadine 5 mg or placebo once daily for 6 weeks. Twice daily, patients rated the severity of CIU symptoms (pruritus, number of hives, and size of largest hive), as well as the impact of CIU symptoms on sleep and daily activity. Patients and investigators jointly evaluated therapeutic response and overall condition. Safety evaluations included the incidence of treatment-emergent adverse events, discontinuations due to adverse events, and changes from baseline in vital signs, laboratory parameters, and ECG intervals. Results Desloratadine was superior to placebo in controlling pruritus and total symptoms after the first dose and maintained this superiority to the end of the study. Measures of sleep, daily activity, therapeutic response, and global CIU status were also significantly better with desloratadine after the first dose; these clinical benefits were also maintained throughout the 6-week study. No significant adverse events occured. Conclusions Desloratadine 5 mg daily is a safe and effective treatment for CIU with significant benefits within 24 h and maintained through the treatment period. [source] Lack of association of antineutrophil cytoplasmic antibodies with joint failure as indicated by joint surgery in rheumatoid arthritisINTERNATIONAL JOURNAL OF RHEUMATIC DISEASES, Issue 1 2005Andrew BROADFOOT Abstract Aim:, The objective of this study was to investigate a possible association in rheumatoid arthritis (RA) of perinuclear antineutrophil cytoplasmic antibodies (pANCA) and joint failure requiring joint surgery as a well-defined functional end point. Methods:, 188 patients with RA according to the American College of Rheumatology criteria, with a mean duration of disease of 18 years, were enrolled in a cross-sectional study. Patients were assessed for history of joint surgery, previous/current therapies, function according to the modified Health Assessment Questionnaire (mHAQ), rheumatoid factor (RF) and clinical and laboratory parameters of disease activity. ANCA were detected using indirect immunofluorescence. Results:, Overall, 36.7% of patients were pANCA positive (including atypical pANCA) and 35.1% of patients had a history of joint surgery. There was no association between the presence of pANCA and joint surgery. No association was demonstrated between ANCA status and other prognostic markers such as RF, previous or current therapies and disease activity or function. Conclusion:, No association between pANCA and joint surgery was demonstrated in this cohort of RA patients. [source] Infusion of hypertonic saline/starch during cardiopulmonary bypass reduces fluid overload and may impact cardiac functionACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 4 2010V. L. KVALHEIM Objective: Peri-operative fluid accumulation resulting in myocardial and pulmonary tissue edema is one possible mechanism behind post-operative cardiopulmonary dysfunction. This study aimed to confirm an improvement of cardiopulmonary function by reducing fluid loading during an open-heart surgery. Materials and methods: Forty-nine elective CABG patients were randomized to an intraoperative infusion of hypertonic saline/hydroxyethyl starch (HSH group) or Ringer's solution (CT group). Both groups received 1 ml/kg/h of the study solution for 4 h after baseline values were obtained (PICCO® transpulmonary thermodilution technique). Net fluid balance (NFB), hemodynamic and laboratory parameters were measured. Results: NFB was four times higher in the CT group compared with the HSH group during the first 6 h post-operatively. The total fluid gain until the next morning was lower in the HSH group, 2993.9 (938.6) ml, compared with the CT group, 4298.7 (1059.3) ml (P<0.001). Normalized values (i.e., %-changes from the baseline) of the cardiac index and the global end diastolic volume index increased post-operatively in both groups. Both parameters were significantly higher at 6 h in the HSH group compared with CT group (P=0.002 and 0.005, respectively). Normalized values of the intrathoracic blood volume index were lower in the HSH group at 6 h post-operatively when compared with the CT group. The PaO2/FiO2 ratio decreased similarly in both groups early post-operatively, but recovery tended to be more rapid in the HSH group. Although serum-sodium and serum-chloride levels were significantly higher in the HSH group, the acid,base parameters remained similar and within the normal range. Conclusions: An intraoperative infusion of HSH during cardiac surgery contributes to reduced fluid loading and an improvement in the post-operative cardiac performance. No adverse effects of the HSH infusion were observed. [source] Chronic urticaria , which clinical parameters are pathogenetically relevant?JOURNAL DER DEUTSCHEN DERMATOLOGISCHEN GESELLSCHAFT, Issue 1 2007A retrospective investigation of 339 patients Summary Background: Urticaria is a clinical reaction pattern triggered by many factors causing liberation of vasoactive substances such as histamine, prostaglandins and kinins. It presents as transient itching wheals which are either limited to the local stimulus area or more widespread. Urticaria is classified according to its duration into acute (duration , 6 weeks) and chronic (duration 6 weeks) forms. Various clinical investigations may be initiated to diagnose the cause. This study critically evaluates the relevance of frequently performed laboratory investigations and searches for infectious foci, as well as the results of physical provocation testing and oral provocation with food additives. Patients and Methods: The laboratory and clinical data of 339 patients who had been treated for urticaria at the Christian-Albrechts-University in Kiel over a period of four years were collected in a data entry form and statistically evaluated. Nominal values were analyzed by their relative and absolute quantities, quantitative parameters with the help of statistical data such as minimum, maximum, median and 25th and 75th percentiles. Results: Chronic recurrent urticaria was most common, accounting for 52% of cases. Women were affected 1.8 times more often than men. One-third of the patients also had angioedema. The medians of all laboratory parameters evaluated were within normal values. Only rarely were elevated antinuclear antibody titers, abnormal thyroid function tests or active infections such as hepatitis B or borreliosis detected. The search for infectious foci identified tonsillitis or sinusitis in almost 50% of analyzed patients. Positive reactions to physical testing occurred in 30% of patients and in 11% to oral provocation with various food additives. Conclusions: This study of a large patient group stresses the relevance of individually- tailored evaluations in patients affected with urticaria rather than an expensive initial broad diagnostic testing. More specific searches should be based on individual clues. [source] Aldosterone receptor antagonism and heart failure: insights from an outpatient clinicJOURNAL OF CLINICAL PHARMACY & THERAPEUTICS, Issue 4 2008R. Mariotti Summary Objective:, In randomized clinical trials, aldosterone antagonists have been shown to reduce mortality and morbidity in heart failure (HF). The aim of the present study was to examine the risk-benefit profile of aldosterone antagonists in routine clinical practice. Methods:, A retrospective analysis, extending over a 1-year period, of the clinical, instrumental and laboratory data of 264 HF outpatients was performed. All patients were on a ,-blocker and an ACE-inhibitor (or angiotensin-II receptor-blocker) and 151 were taking an aldosterone antagonist. Results:, At baseline, subjects treated with aldosterone antagonists had a higher NYHA class, a larger left-ventricular end-diastolic volume, a worse ejection fraction and a higher systolic pulmonary arterial pressure (sPAP). During follow-up, a greater reduction in sPAP and a tendency towards improved systolic and diastolic function were observed in subjects treated with aldosterone antagonists. Moreover, clinical and laboratory parameters did not deteriorate in patients taking aldosterone antagonists. Mortality rates were similar in the two groups (8·6% vs. 8·8%, P = NS). Conclusions:, The use of aldosterone antagonists in HF is associated with an improvement in cardiac function and is well tolerated. In the present study, patients administered these agents had a comparable clinical outcome to that of the control group, despite important differences in baseline risk. [source] Predicting and monitoring cancer treatment response with diffusion-weighted MRIJOURNAL OF MAGNETIC RESONANCE IMAGING, Issue 1 2010Harriet C. Thoeny MD Abstract An imaging biomarker that would provide for an early quantitative metric of clinical treatment response in cancer patients would provide for a paradigm shift in cancer care. Currently, nonimage based clinical outcome metrics include morphology, clinical, and laboratory parameters, however, these are obtained relatively late following treatment. Diffusion-weighted MRI (DW-MRI) holds promise for use as a cancer treatment response biomarker as it is sensitive to macromolecular and microstructural changes which can occur at the cellular level earlier than anatomical changes during therapy. Studies have shown that successful treatment of many tumor types can be detected using DW-MRI as an early increase in the apparent diffusion coefficient (ADC) values. Additionally, low pretreatment ADC values of various tumors are often predictive of better outcome. These capabilities, once validated, could provide for an important opportunity to individualize therapy thereby minimizing unnecessary systemic toxicity associated with ineffective therapies with the additional advantage of improving overall patient health care and associated costs. In this report, we provide a brief technical overview of DW-MRI acquisition protocols, quantitative image analysis approaches and review studies which have implemented DW-MRI for the purpose of early prediction of cancer treatment response. J. Magn. Reson. Imaging 2010. © 2010 Wiley-Liss, Inc. [source] Cytokine responses in a severe case of glandular fever treated successfully with foscarnet combined with prednisolone and intravenous immunoglobulinJOURNAL OF MEDICAL VIROLOGY, Issue 1 2009Christine Ma Abstract Viral loads and cytokine responses Epstein,Barr virus (EBV) were measured in an 18-year-old boy with severe glandular fever complicated by a mild anaemia, severe thrombocytopaenia and neutropaenia. Hepatosplenomegaly was detected by abdominal ultrasound in the presence of significant hepatitis. Cytokine testing demonstrated elevated cell-mediated Th1 (IFN-,, IL-12, sTNFR1, CXCL10, CXCL9 and CCL3) and humoral Th2 (IL-4) immune responses. Serum antibodies to EBV virus capsid antigen (VCA) IgM and IgG antibodies were detected, together with a raised EBV DNA level (up to about 70,000 DNA copies/mL) in the acute phase of the illness. This EBV DNA load decreased rapidly in response to treatment with a combination of foscarnet, intravenous immunoglobulin and prednisolone, and the boy's symptoms settled eventually after approximately 50 days of illness, following this combined antiviral and immune-modulating therapy. Detailed immunological, virological, haematological and biochemical laboratory parameters are presented to document this patient's severe EBV disease and eventual recovery. J. Med. Virol. 81:99,105, 2009. © 2008 Wiley-Liss, Inc. [source] Experimental hepatitis A virus infection in guinea pigsJOURNAL OF MEDICAL VIROLOGY, Issue 4 2001Britt Hornei Abstract Although many of the properties of hepatitis A virus (HAV) are known, several aspects of HAV pathogenesis are still not understood, such as the mechanism underlying the hepatotropism or HAV replication in extrahepatic sites. Detailed studies of these aspects were hampered mostly by the lack of accessible animal models, since only nonhuman primates are susceptible to experimental infections. An alternative animal model would also be of interest to assess the primary replication site and for the evaluation of the safety and efficacy of vaccines. A study was undertaken to determine whether HAV can infect guinea pigs and whether they are useful as a model for studying aspects of HAV pathogenesis and for the evaluation of vaccines. HAV variants adapted to primate or guinea pig tissue culture were used to inoculate guinea pigs intraperitoneally and by the oral route. The animals were observed for clinical disease, shedding of HAV in stools, viremia, seroconversion, evidence for liver damage by biochemical liver function tests, virus presence in the liver, development of hepatic histopathological changes, and occurrence of HAV in extrahepatic organs. The animals developed an active, clinically inapparent infection with specific histopathological changes in the liver. Although virus replication occurred, as shown by RT-PCR and isolation of infectious virus from feces and serum, it seems unlikely that guinea pigs are suitable for studying the clinical features of hepatitis A, because the clinical and laboratory parameters remained normal. However, guinea pigs appear useful for studying some aspects of HAV pathogenesis and for testing the safety of vaccines. J. Med. Virol. 64:402,409, 2001. © 2001 Wiley-Liss, Inc. [source] | ||||||||||||||||||||||||||||||||||