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Biomedical subjects

A Hamwi

Publications and source records attributed to A Hamwi.

At least 19 recordsLinked to original sources

Pharmacokinetics of teicoplanin during continuous hemofiltration with a new and a 24-h used highly permeable membrane: rationale for therapeutic drug monitoring-guided dosage.

OBJECTIVE: Continuous venovenous hemofiltration (CVVH) is widely used in the management of critically ill patients, but only few administration guidelines for antimicrobial drugs are available. It is unclear whether the use of a filter for more than 24 hours might lead to less efficient extraction. This study describes the pharmacokinetics of teicoplanin during CVVH using a highly permeable membrane. METHODS: Pharmacokinetics of teicoplanin during continuous hemofiltration with a new (group 1) and a 24-h used (group 2), highly permeable polyamide membrane were assessed in 3 patients. RESULTS: The teicoplanin serum concentrations (44.0 +/- 18.5 mg/l vs 109.5 +/- 34.5 mg/l) and half-life of teicoplanin (4.6 +/- 1.1 h vs 5.2 +/- 0.7 h) differed significantly between the 2 groups indicating a smaller elimination of the drug on the second day. Substantial binding of teicoplanin to filter membranes could explain this observation. CONCLUSION: The results suggest that daily adjustment of the dosage is necessary to achieve sufficient teicoplanin concentrations and a fixed dosage recommendation is not suitable for this drug.

Anti-Bacterial Agents↗

The effect of calisthenic home exercises on postmenopausal fractures--a long-term observational study.

OBJECTIVES: To evaluate the long-term effects of calisthenic home exercises on the incidence of fractures in postmenopausal women. DESIGN: Controlled long-term observational study. METHODS: Postmenopausal women between 45 and 75 years of age who had been randomly assigned to an exercise or control group in the course of a previous study conducted 5-10 years ago, were invited for follow-up. The number of fractures before and during the observation time were recorded by means of a questionnaire. Vertebral deformities due to fractures were diagnosed by X-rays at entry and at follow-up. Walking speed, muscle strength, static posturography, and maximum oxygen uptake were measured in addition. RESULTS: After an average follow-up time of 7.6+/-1.1 years, 73 women of the exercise group and 64 subjects of the control group were investigated. Thirty-three per cent (n=24) of the exercise group reported to have exercised continuously at least three times a week for 20 min. No intergroup differences between the compliant and non-compliant exercisers and the control group were seen in the number of fractures. However, the incidence of fracture was lowest in women with a baseline bone mass less than one standard deviation (SD) below the mean for young adults (high BMC) and highest in those with more than 2.5 SD below the mean for young adults (low BMC) (P<0.001, odds ratio 2.9 [95% CI, 1.59-5.39]). CONCLUSION: This long-term follow-up did not produce any evidence that prescription of a calisthenic home exercise program may prevent fractures in postmenopausal women aged between 61+/-6.4 and 68+/-6.5 years.

Aged↗

Characterization of (123)I-vascular endothelial growth factor-binding sites expressed on human tumour cells: possible implication for tumour scintigraphy.

To explore the possibility of vascular endothelial growth factor (VEGF) receptor scintigraphy of primary tumours and their metastases, we analysed the binding properties of (123)I-labelled VEGF(165) ((123)I-VEGF(165)) and (123)I-VEGF(121) to human umbilical vein endothelial cells (HUVECs), several human tumour cell lines (HMC-1, A431, KU812, U937, HEP-1, HEP-G2, HEP-3B and Raji), a variety of primary human tumours (n = 40) and some adjacent non-neoplastic tissues as well as normal human peripheral blood cells in vitro. Two classes of high-affinity (123)I-VEGF(165)-binding site were found on the cell surface of HUVECs. In contrast, one class of high-affinity binding sites for (123)I-VEGF(165) was found on HMC-1, A431, HEP-1, HEP-G2, HEP-3B and U937 cells as well as many primary tumours. For (123)I-VEGF(121), a single class of high-affinity binding site was found on certain cell lines (HUVEC, HEP-1 and HMC-1) and distinct primary tumours (primary melanomas, ductal breast cancers and ovarian carcinomas as well as meningiomas). Tumour cells expressed significantly higher numbers of VEGF receptors compared with normal peripheral blood cells and adjacent non-neoplastic tissues. Immunohistochemical staining revealed that the VEGF receptor Flk-1 is expressed to a much higher extent within malignant tissues compared with neighbouring non-neoplastic cells. We observed significantly greater specific binding of (123)I-VEGF(165) and (123)I-VEGF(121) to a variety of human tumour cells/tissues compared with the corresponding normal tissues or normal peripheral blood cells. In comparison with (123)I-VEGF(121), (123)I-VEGF(165) bound to a higher number of different tumour cell types with a higher capacity. Thus, (123)I-VEGF(165) may be a potentially useful tracer for in vivo imaging of solid tumours.

Animals↗

Serum calcium in thyroid disease.

Thyroid hormones are believed to influence calcium metabolism. In the present prospective study we investigated the influence of various thryroid diseases on serum calcium levels. In addition to screening for thyroid diseases we measured serum calcium concentrations (S-Ca) in individuals who came to our outpatient service for thyroid diseases from 1992 to 1998. 13,387 persons, among them 9017 patients with thyroid diseases and 4370 persons without thyroid dysfunction, were studied. S-Ca was found to be higher in patients with hyperthyroidism (2.36 +/- 0.11 mmol/L n = 1201, p < 0.05) than in those with subclinical hyperthyroidism (2.33 +/- 0.11 mmol/L, n = 494), with euthyroid goiter (2.32 +/- 0.10 mmol/l, n = 5599), with hypothyroidism (2.31 +/- 0.11 mmol/L, 344), with subclinical hypothyroidism (2.32 +/- 0.10 mmol/L, n = 1290) and in healthy persons (2.31 +/- 0.11 mmol/L, n = 4370). 173/13,387 persons had serum calcium levels < 2.1 mmol/L, among them 31 patients with hypoparathyroidism after strumectomy (31/592) and 2 patients with primary hypoparathyroidism. 106/13,387 persons showed a S-Ca of > 2.6 mmol/L, which in 30 cases was due to primary hyperparathyroidism. Of 55 persons with S-Ca of > 2.6 mmol/L and without any other reason for hypercalcaemia, 31 were found to be in a hyperthyroid state. In conclusion, a clinically not relevant influence on S-Ca was demonstrated in patients with hyperthyroidism as compared with other thyroid diseases and individuals with no thyroid diseases. Measurement of S-Ca in every patient being referred to a thyroid outpatient department is recommended because of the frequent occurrence of postoperative hypoparathyroidism and primary hyperparathyroidism in this setting.

Adolescent↗

The predictive value of MDR1, CYP2C9, and CYP2C19 polymorphisms for phenytoin plasma levels.

Phenytoin, an anticonvulsant, exhibits nonlinear pharmacokinetics with large interindividual differences. Because of its small therapeutic range with the risk of therapeutic failure or adverse drug effects in susceptible persons, therapeutic drug monitoring is frequently applied. The interindividual differences in dose response can partially be explained by known genetic polymorphisms in the metabolic enzyme CYP2C9 but a large deal of individual variability remains still unexplained. Part of this variability might be accounted for by variable uptake of phenytoin, which is a substrate of p-glycoprotein, encoded by the human MDR1 gene. We evaluated, whether phenytoin plasma levels correlate with a polymorphism in the MDR1 gene, C3435T, which is associated with intestinal PGP activity. Genotyping and analyses of plasma levels of phenytoin and metabolites in 96 healthy Turkish volunteers showed that the MDR1C > T3435 polymorphism affects phenytoin plasma levels (P = 0.064) and the metabolic ratio of p-HPPH vs phenytoin (MDR1*TT genotype, P = 0.026). The MDR1*CC genotype is more common in volunteers with low phenytoin levels (P < or = 0.001, chi2 test). A combined analysis of variable alleles of CYP2C9, 2C19 and MDR1 revealed that the number of mutant CYP2C9 alleles is a major determinant, the number of MDR1*T alleles further contributes to the prediction of phenytoin plasma levels and CYP2C19*2 does not explain individual variability. The regression equation that fitted the data best included the number of mutant CYP2C9 and MDR*T alleles as predictory variables and explained 15.4% of the variability of phenytoin data (r2 = 0.154, P = 0.0002). Furthermore, analysis of CYP2C9 and MDR1 genotypes in 35 phenytoin-treated patients recruited from therapeutic drug monitoring showed that combined CYP2C9 and MDR1 analysis has some predictive value not only in the controlled settings of a clinical trial, but also in the daily clinical practice.

Adolescent↗

Markers of bone turnover in postmenopausal women receiving hormone replacement therapy.

We investigated the effects of hormone replacement therapy (n = 27) on biochemical markers of bone turnover in a cross-sectional study of 127 postmenopausal women (according to WHO guidelines 18 patients had normal bone mineral density and 109 suffered from bone loss). Urinary excretion of free deoxypyridinoline and C- or N-telopeptide fragments of type I collagen served as bone resorption markers, serum osteocalcin as a bone formation marker. In women with no hormone replacement therapy, only C- and N-telopeptides correlated significantly with the lumbal T-score as an index for bone mineral density. Patients with bone loss receiving hormone replacement therapy exhibited significantly lower C-telopeptide, N-telopeptide and osteocalcin levels than those with no therapy (mean -45%, -43% and -26%, respectively), while deoxypyridinoline showed no significant differences. Among the markers investigated, C- and N-telopeptides seemed to be more reliable to detect therapeutic effects on bone metabolism. We present a preliminary model to evaluate bone turnover and resorption/formation rate.

Aged↗

Pancreatic elastase 1 in stool: variations within one stool passage and individual changes from day to day.

Concentration of fecal pancreatic elastase 1 has been claimed to be a highly sensitive and specific noninvasive test for exocrine pancreatic function. The aim of our study was to investigate variations in elastase concentration within one stool passage and from day to day. For the analysis of the variation of fecal elastase within one stool passage, we utilized 3 different samples collected from 8 patients. Further, we assessed the individual day to day variation of fecal elastase using stools collected on 3 consecutive days from 40 patients. For the determination of pancreatic elastase 1 in stool we used an ELISA kit. We found a relatively considerable variation of fecal elastase concentration within one stool passage (n = 8, mean CV = 22%, range 4.6-83.1%) and from day to day (n = 40; mean CV = 26%, range 2.4-61.1%). Therefore, we recommend routine analysis of more than 1 stool sample collected on different days for fecal elastase and to use a borderline area of +/- 25% of the recommended cut off of 200 micrograms/g stool for the diagnosis of pancreatic insufficiency.

Enzyme-Linked Immunosorbent Assay↗

Inflammatory response and myocardial injury following coronary artery bypass grafting with or without cardiopulmonary bypass.

OBJECTIVE: In coronary artery bypass grafting (CABG) without cardiopulmonary bypass (CPB) the inflammatory response is suggested to be minimized. Coronary anastomoses are performed during temporary coronary occlusion. Inflammatory response and myocardial ischaemia need to be studied in a randomized study comparing CABG in multivessel disease with versus without CPB. METHODS: Following randomization 30 consecutive patients received CABG either with (n=16) or without CPB (n=14). Primary study endpoints were parameters of the inflammatory response (interleukin (IL)-6, interleukin-10, ICAM-1, P-selectin) and of myocardial injury (myoglobin, creatine kinase-MB (CK-MB), troponin I) (intraoperatively, 4, 8, 16, 24 and 48 h after surgery). The secondary endpoint was clinical outcome. RESULTS: The incidence of major (death: CABG with CPB n=1, not significant (n.s.)) and minor adverse events (wound infection: with CPB n=2, without CPB n=1, n.s. ; atrial fibrillation: with CPB n=3, without CPB n=2, n.s.) was comparable between both groups. The release of IL-6 was comparable during 8 h of observation (n.s.). Immediately postoperatively IL-10 levels were higher in the operated group with CPB (211.7+/-181.9 ng/ml) than in operated patients without CPB (104.6+/-40.3 ng/ml, P=0.0017). Thereafter no differences were found between both groups. A similar pattern of release was observed in serial measures of ICAM-1 and P-selectin, with no difference between both study groups (n.s.). Eight hours postoperatively the cumulative release of myoglobin was lower in operated patients without CPB (1829.7+/-1374. 5 microg/l) than in operated patients with CPB (4469.8+/-4525.7 microg/l, P=0.0152). Troponin I release was 300.7+/-470.5 microg/l (48 h postoperatively) in patients without CPB and 552.9+/-527.8 microg/l (P=0.0213). CK-MB mass release was 323.5+/-221.2 microg/l (24 h postoperatively) in operated patients without CPB and 1030. 4+/-1410.3 microg/l in operated patients with CPB (P=0.0003). CONCLUSIONS: This prospective randomized study suggests that in low-risk patients the impact of surgical access on inflammatory response may mimic the influence of long cross-clamp and perfusion times on inflammatory response. Our findings indicate that multiregional warm ischaemia, caused by snaring of the diseased coronary artery, causes considerably less myocardial injury than global cold ischaemia induced by cardioplegic cardiac arrest.

Adult↗

Cyclosporine metabolism in patients after kidney, bone marrow, heart-lung, and liver transplantation in the early and late posttransplant periods.

Cyclosporine is used in the prevention of allograft rejection. Owing to its narrow therapeutic index, regular monitoring of the whole blood levels of cyclosporine is required. We observed that immunoassays measured significantly higher cyclosporine levels than did high-performance liquid chromatography (HPLC) over time after transplantation. As cyclosporine metabolites cross-react even with immunoassays, this observation might be due to alterations of the cyclosporine metabolism. We analyzed cyclosporine metabolite concentrations in the early and in the late posttransplantation periods in 127 patients after kidney, bone marrow, heart-lung, and liver transplantation by HPLC and determined whole blood levels of cyclosporine by 4 immunoassays (enzyme-multiplied immunoassay [EMIT], cloned enzyme donor immunoassay [CEDIA], AxSYM [Abbott Laboratories, Chicago, IL], and TDx [Abbott Laboratories]). Despite reduced dose, we found significantly higher cyclosporine concentrations measured by the EMIT, AxSYM, and TDx assays in various patient groups. These results are due to the increased metabolite/cyclosporine ratio in the late posttransplantation period. In particular, the metabolites AM1 and AM19 increased significantly over time in bone marrow transplant recipients. Therefore, cyclosporine levels measured by immunoassays should be interpreted with caution.

Bone Marrow Transplantation↗

Evaluation of four automated methods for determination of whole blood cyclosporine concentrations.

Cyclosporine is a widely used and potent immunosuppressant drug with a narrow therapeutic index. Therefore, cyclosporine concentrations should be monitored closely. Various automated immunologic methods for cyclosporine whole blood determinations are available. Two new methods, fluorescence polarization immunoassay (FPIA) for the AxSYM by Abbott Laboratories, Chicago, IL, and the cloned enzyme donor immunoassay (CEDIA) by Boehringer Mannheim, Mannheim, Germany, have been introduced. In addition, Dade Behring improved its enzyme multiplied immunoassay (EMIT) assay. The present study evaluated all 3 new methods in comparison with high-performance liquid chromatography (HPLC) and the FPIA for the TDx analyzer. We measured whole blood cyclosporine concentrations of 179 samples obtained from 127 patients after kidney, bone marrow, heart-lung, and liver transplantation. All 4 automated immunologic methods can be used for routine measurement of cyclosporine whole blood concentrations. Disadvantages, such as higher cross-reactivity (Abbott TDx, CEDIA) or a limited linearity range (EMIT), are accompanied by advantages, such as a high precision (Abbott TDx) or an easy sample handling procedure (CEDIA). Information presented in this article should help to find the most adequate cyclosporine method for each medical laboratory.

Antibodies, Monoclonal↗

Myocardial revascularization without cardiopulmonary bypass in pigs: a comparison between beta-blockers and Ca2+-channel blockers.

The purpose of this study was to develop the surgical technique for internal mammary artery grafting on the beating heart. In 10 pigs, heart rate was reduced with esmolol (n = 5) or verapamil (n = 5). In addition, the anti-ischaemic and anti-arrhythmic potencies of these drugs were investigated. Haemodynamics, mechanical function and ischaemia-sensitive laboratory measurements were assessed perioperatively. There were no differences in pre-ischaemic data including ischaemic clamping time of the left anterior descending artery. At the end of ischaemia haemodynamic parameters were significantly lower in the esmolol-group (P < 0.05). In the verapamil-group, one pig died from ventricular fibrillation during ischaemia, and one showed fibrillation during reperfusion (P < 0.01). There were no differences in cardiac function or enzymes between the groups. Reduction of heart rate was provided by both drugs, but no conclusive evidence was provided with regard to additional anti-ischaemic and anti-arrhythmic protection.

Adrenergic beta-Antagonists↗

Disturbed latex immunoassays for C-reactive protein and ferritin in a renal transplant patient due to polyclonal IgM hypergammaglobulinaemia.

BACKGROUND: C-reactive protein (CRP) and ferritin serum levels represent routine laboratory parameters in the monitoring of renal failure patients. Analysis of CRP, ferritin and other serum proteins can be performed using latex-enhanced or non-latex-enhanced immunoassays. We report on a renal transplant patient with polyclonal IgM hypergammaglobulinaemia having markedly elevated serum CRP and ferritin levels (as detected by latex-enhanced immunoassays) in the absence of clinical signs of an infectious or malignant disorder. METHODS: CRP and ferritin serum levels were determined with various immunoassays with and without latex enhancement. To characterize the causative agent for the elevated CRP and ferritin values, the patient's and a control serum were fractionated by gel filtration on a Sephacryl S-300 column. Serum fractions were subjected to further analysis for reactivity in CRP and ferritin assays. In addition, patient's serum samples were investigated for reactivity with various other latex-based immunoassays (rheumatoid factor, antistreptolysin O, antistreptococcal DNase B). RESULTS: Using latex-enhanced CRP and ferritin immunoassays, markedly elevated serum levels were obtained (CRP 726 mg/l determined by turbidimetry, 398 mg/l determined by nephelometry; ferritin, 20,000 micrograms/l determined by turbidimetry). In contrast, assays without latex enhancement revealed levels within the normal range for both serum proteins (CRP < 5 mg/l, ferritin 52 micrograms/l). The analysis of the patient's serum by gel filtration revealed an interference of the patient's IgM with latex particles used in the CRP and ferritin assays. CONCLUSION: Our study demonstrates that even polyclonal IgM hypergammaglobulinaemia can disturb a large array of latex-enhanced immunoassays used for routine diagnostic procedures. This is of particular interest for the management of allograft recipients in whom monoclonal and polyclonal gammaglobulinaemia are frequently observed. We therefore recommend reanalysis of the respective plasma proteins by latex-free assays in patients with hypergammaglobinaemia showing no clinical signs of an acute infectious disease or malignant disorder.

C-Reactive Protein↗

Comparison of four rapid D-Dimer tests for diagnosis of pulmonary embolism.

Aim of this study was to evaluate rapid D-Dimer tests for their utility in diagnosis of acute pulmonary embolism (PE). Tests were performed in 183 consecutive pats referred for lung scanning because of clinically suspected PE. According to lung scans and the clinical course of disease 19 pats were classified to have PE with high probability and 164 with low probability. An ELISA (Agen) was used as the D-Dimer reference, and results compared with those of a turbidimetric (Behring), an immunofiltration (Nycomed), latex plasma and whole blood agglutination test (both Agen). There was a poor correlation between the turbidimetric test and either the ELISA (R = 0.38) and immunofiltration test (R = 0.49). The correlation between the ELISA and immunofiltration test was better (R = 0.73). The qualitative latex and whole blood agglutination tests were better fitted to ELISA since positive and negative samples were overlapped only in their 1st and 9th percentiles of ELISA values. The whole blood agglutination test was positive at lower ELISA values than the latex test. The highest sensitivity test for PE was the immunofiltration test (95%) (500ng/mL cut-off), followed by the turbidimetric method (89%) (66ng/mL), the ELISA (89%) (300ng/mL), the whole blood test (88%) and the latex test (68%). Specificity was lowest for the immunofiltration test (33%), intermediate (57-65%) for the turbidimetric and whole blood agglutination tests, and highest for the ELISA and the most insensitive latex test (76/77%). The whole blood assay was found to be the fastest and most suitable for bed site testing but weak positives were difficult to read. The immunofiltration test required plasma preparation but allowed objective semiquantitation of results. The less rapid turbidimetric assay was fully quantitative and objective.

Adolescent↗

Elevated liver isoenzymes of alkaline phosphatase and disease activity in patients with Crohn's disease.

Serum alkaline phosphatase (ALP) and its isoenzymes - liver (L-ALP), fast liver (F-ALP; also called high-molecular-weight ALP), bone (B-ALP) and intestinal (I-ALP) - were measured by agarose electrophoresis after pretreatment of sera with neuraminidase in 100 patients with Crohn's disease (CD) and 100 age-matched healthy controls. Total ALP was increased in 25 patients whereas the isoenzymes F-ALP, L-ALP, B-ALP, I-ALP were increased in 64, 84, 16 and 8%, respectively. But also in patients with CD and with normal ALP the isoenzymes were high in 39, 15, 1 and 1%, respectively. Total ALP, L-ALP and F-ALP correlated with gamma-glutamyltransferase (GGT) (tau = 0.22, 0.20 and 0.26, respectively, p < 0.05), but F-ALP also correlated with parameters of disease activity such as Crohn's disease activity index (CDAI), orosomucoid (OM) and erythrocyte sedimentation rate (tau = 0.28, 0.23 and 0.37, respectively, p < 0.001). In 38 patients, ALP and isoenzymes were controlled within 6 months. In these patients there were correlations between changes of total ALP and F-ALP with changes of inflammatory activity such as CDAI (tau = 0.31, p = 0.07 and tau = 0.30, p = 0.01) or OM (tau = 0.26 and 0.25, p < 0.05). Therefore, ALP seems to be influenced by inflammatory activity mainly via F-ALP which could be a marker of disease activity.

Adolescent↗

Quantitative measurement of HbA1c by an immunoturbidimetric assay compared to a standard HPLC method.

Determination of hemoglobin A1c (HbA1c) is one of the most important monitoring procedures for long-term control of diabetes mellitus. Several analytical methods have been developed for the measurement of glycohemoglobin (GHb). Those most frequently used are ion-exchange chromatography for HbA1c and affinity chromatography for total GHb. In this study, a new turbidimetric immunoassay for HbA1c (Boehringer Mannheim, Germany) was evaluated that was performed on a Hitachi 911 clinical chemistry analyzer (Boehringer Mannheim). Good linearity in the range of 5% to 15% HbA1c, within-run and between-run coefficients of variation ranging from 2.4% to 5.9% were obtained. Results of 179 diabetic and nondiabetic patients showed good correlation to those of a routine HPLC method (r = 0.96). In addition, HbA2, HbS, and HbF in samples from nondiabetic patients were not detected by the immunoturbimetric assay and the "labile" HbA1c fraction (Schiff base) did not interfere with the new test.

Chromatography, High Pressure Liquid↗

[Should Doppler echography in the diagnosis of the extra-cardiac sites of atherosclerosis be routine in patients with coronary disease? Apropos of 248 cases].

Doppler ultrasound investigation of cervical and aorto-iliac arteries, performed in 248 patients investigated by coronary angiography (including 80% with coronary heart disease: 23% single-vessel, 23% two-vessel and 34% three-vessel disease) confirmed the frequency of dissemination of the atheromatous process (in the cervical vessels: non-stenotic atheroma: 45%, significant single- or multi-vessel stenoses: 16%, in the aorto-iliac vessels: non-stenotic atheroma: 32.8%, significant stenoses: 17.2%), which has been known for a long time. The unreliability of clinical examination, the reliability, safety and low cost of ultrasound, the discovery of a considerable number of critical, potentially dangerous arterial lesions, some of which may require a surgical procedure or angioplasty (3.4%), the value of assessing, either before coronary angiography or before cardiac surgery, certain specific arterial territories such as the aortic bifurcation and subclavian vessels, justify systematic use of this examination in coronary patients, particularly before coronary angiography and always before coronary surgery.

Adult↗