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Joris Delanghe

Publications and source records attributed to Joris Delanghe.

At least 19 recordsLinked to original sources
PubMed2007

The glomerular filtration rate in an apparently healthy population and its relation with cardiovascular mortality during 10 years.

AIMS: Moderate-to-severe chronic renal failure is an established risk factor for cardiovascular disease and mortality. However, most studies have been performed in selected populations and the impact of very small decrements of renal function on long-term cardiac morbidity and mortality has not yet been established. Also, the cut-off level of glomerular filtration rate (GFR) from which cardiovascular risk increases has not exactly been established. This study wants to address these questions. METHODS AND RESULTS: Ten year follow-up of a representative population-based cohort comprised 8913 randomly selected, apparently healthy participants. Participants were randomly drawn from Belgian voting lists. Cardiovascular risk factors were noted. Serum creatinine values were corrected to isotope dilution mass spectrometry standard, and GFR was calculated using the recently modified 'modification of diet in renal disease' equation. Participants were followed for 10 years, and cause-specific death was registered by analysis of death certificates. The probability to die from all causes or from cardiovascular causes during the 10 year follow-up period increased in each quartile of GFR, even after correction for different other comorbid conditions. CONCLUSION: Even mild renal failure is an independent risk factor for cardiovascular mortality within 10 years in an apparently healthy unselected population. This detrimental effect starts already at a relatively high GFR of 90 mL/min/1.73 m2 and remains present after correction for other established cardiovascular risk factors.

Cardiovascular Diseases↗
PubMed2006

Soluble N-cadherin in human biological fluids.

Classical cadherins such as E-, P- and N-cadherin are transmembrane proteins that mediate cell-cell adhesion, and are important in embryogenesis, maintenance of tissue integrity and cancer. Proteolytic shedding of the extracellular domain results in the generation of soluble E-, P- or N-cadherin ectodomains. Circulating soluble E- and P-cadherin have been described in the serum, and elevated levels were detected in cancer patients when compared with healthy persons. Here we report the presence of soluble N-cadherin, a 90-kD protein fragment, in the serum of both healthy persons and cancer patients, using a direct ELISA and immunoprecipitation. A correlation was found between prostate specific antigen and soluble N-cadherin, and significantly elevated levels were detected in prostate cancer follow-up patients. The N-cadherin protein is neo-expressed by carcinomas of the prostate, and is responsible for epithelial to fibroblastic transition. This is reflected by the higher concentrations of soluble N-cadherin in prostate cancer patients than in healthy persons.

Breast Neoplasms↗
PubMed2006

Monoclonal immunoglobulin with antitransferrin activity: A rare cause of hypersideremia with increased transferrin saturation.

Two unusual but similar cases of very high serum iron, extremely high transferrin concentrations (5.4 to 6.5 g/L), and increased transferrin saturation are reported. No anemia or microcytosis was observed. The ferritin concentration remained within the normal range, and no iron overload was observed. In one case, the in vivo half-life of 59Fe-labeled transferrin was shown to be prolonged (206 minutes versus 75 minutes for controls). In both patients, a monoclonal IgG was observed in the serum. The association between serum transferrin and monoclonal IgG was demonstrated by Western blot analysis and affinity chromatography. We suggest that the transferrin bound to the monoclonal IgG molecule has a prolonged half-life in the circulation, leading to high transferrin concentrations, and that the increased serum iron values prevent the onset of anemia. The antitransferrin activity of monoclonal antibody should be added to the list of situations accounting for elevated serum iron with elevated transferrin saturation.

Antibodies, Monoclonal↗
PubMed2006

Epidemiological evidence for an association between habitual tea consumption and markers of chronic inflammation.

BACKGROUND: Tea consumption has been inversely related to the risk of cardiovascular disease, but the mechanism behind this cardioprotective role is not fully understood. In vitro and animal model studies suggest an anti-oxidative and/or anti-inflammatory role. We aimed at investigating the association between tea drinking and indicators of low-grade inflammation in humans. METHODS: We used observational data from 1031 healthy men participating in a larger cross-sectional study (BELSTRESS). Tea consumption was determined according to a semi-quantitative food frequency questionnaire. Blood samples were analysed for C-reactive protein (CRP), serum amyloid A (SAA), serum haptoglobin and plasma fibrinogen. RESULTS: Of all participants, 22% consumed tea regularly while 10% drank more than two cups per day. Tea drinkers were less obese, smoked less and drank less alcohol and coffee. CRP, SAA and haptoglobin were significantly associated with tea consumption, the effect being graded for SAA. Multivariate analysis did confirm the independence of the observed beneficial role of tea drinking. Fibrinogen levels were however not different between habitual tea consumers and non-consumers. Coffee drinking proved unrelated to chronic inflammation. CONCLUSION: Tea drinking might be of interest in reducing the inflammatory process underlying cardiovascular disease. In light of the fact that tea is the most consumed beverage in the world after water, our findings might be of importance from a public health perspective.

Adult↗
PubMed2006

Comparison of triglyceride concentration with lipemic index in disorders of triglyceride and glycerol metabolism.

BACKGROUND: In plasma, triglycerides (TG) are transported in lipoprotein particles (mainly chylomicrons, very low-density and low-density lipoprotein). Turbidimetry (bichromatically at 660 and 700 nm) allows measurement of the lipemic (L) index. We explored the use of this index, in combination with a TG assay, to detect errors due to non-fasting, to assess abnormalities in TG metabolism and to detect patients with glycerol kinase deficiency (GKD). METHODS: We collected 2441 patient samples. Normolipidemic (n=2347), type IV hyperlipidemic (n=80), postprandial samples (n=22) and serial dilutions of Intralipid with saline (n=6) were selected. One patient presenting with GKD was included, as well as two patients with type I and type V hyperlipoproteinemia, respectively. RESULTS: We introduced the use of the ratio between the logarithm of serum triglycerides and that of the L-index (TG/L ratio). CONCLUSION: Although the proposed TG/L-index ratio cannot be regarded as an alternative for the accurate diagnosis of lipid disorders, it provides additional information about TG-containing particles.

Glycerol Kinase↗
PubMed2006

Rheumatoid factor interference in the determination of carbohydrate antigen 19-9 (CA 19-9).

BACKGROUND: Investigation of a 61-year-old Caucasian male suffering from fatigue and weight loss led to the finding of a carbohydrate antigen 19-9 (CA 19-9) concentration of 80 kU/L using an ADVIA Centaur analyser. Determination of CA 19-9 on Vidas, AxSYM and Architect i2000 systems gave normal results. His rheumatoid factor concentration was very high (900 kIU/L) and assay interference was suspected. METHODS: Besides using several laboratory procedures to show the cause of the interference, we tried to estimate the frequency of the suspected interference. Therefore, two studies were performed. The first was carried out in a multicentre setting using four different CA 19-9 methods on 51 randomly selected samples with high rheumatoid factor concentrations and ten samples containing no or very low rheumatoid factor. In the second study we used heterophilic blocking tubes for 68 routinely analysed samples with CA 19-9 concentrations ranging between 37 and 250 kU/L using an ADVIA Centaur analyser. RESULTS: In the multicentre study we found eight discrepant CA 19-9 results, but only one was clearly due to interference. We showed that the interference detected, just as in the index case, was caused by rheumatoid factor. The other discrepancies could not be explained, but are probably related to method-dependent differences. In the 68 routinely analysed samples, no interference could be shown using the heterophilic blocking tubes. CONCLUSIONS: Although interferences in the CA 19-9 assay are not frequent, the ADVIA Centaur system appears to be more sensitive to rheumatoid factor interference. The lack of standardisation remains an important issue for this assay. The determination of CA 19-9 during the follow-up of patients should be performed using a single method. If, however, there is any clinical doubt about a result, CA 19-9 should be determined using another method to exclude possible interferences.

Artifacts↗
PubMed2005

The importance of standardization of creatinine in the implementation of guidelines and recommendations for CKD: implications for CKD management programmes.

BACKGROUND: In an attempt to reduce late referral and to improve the care of patients with chronic kidney disease (CKD), different organizations have issued guidelines on when to refer patients to the nephrologist. Most suggest referral of patients with a GFR below 60 ml/min/1.73 m2, and demand referral if the GFR is below 30 ml/min/1.73 m2. It is recommended to use the abbreviated MDRD equation to estimate GFR. This formula is, however, sensitive to the creatinine assay methodology. In addition, the impact of the implementation of such guidelines on the nephrology practice has never been evaluated. This study (i) identifies the true burden of CKD in a population and simulates the effects of a 100% implementation of the guidelines on the nephrology work load, and (ii) evaluates the validity of the estimated GFR using the abbreviated MDRD formula when routinely provided. METHODS: Different laboratories (both hospital and private) in our region were asked to report on all the serum creatinine values performed during the first week of December 2004. If patients had more than one determination, only the lowest serum creatinine value was retained. Patients already known to a nephrology unit were not included. GFR was calculated using the abbreviated MDRD, using the serum creatinine as reported by these laboratories, or after correction to the MDRD-standard using different published equations. RESULTS: 20,108 patients, with a mean age of 53.4+/-16.2 years, 48% females, had at least one serum creatinine determination in the observation period. According to the K/DOQI CKD classification, 20.2, 1.6 and 0.8% of females and 13.3, 1.6 and 0.6% of males were in stage 3, 4 and 5, respectively, when the abbreviated MDRD formula was used with the serum creatinine value as reported by the laboratories. Important differences in classifications were obtained when the different correction formulae for creatinine were applied. According to the current recommendations, this would lead to a mandatory referral of 1650-2400 CKD stage 4 patients per 100 000 inhabitants and a suggested referral of another 4100-15 360 CKD stage 3 patients per 100,000 inhabitants to a nephrology unit. CONCLUSION: Implementation of the current guidelines for referral of CKD patients to nephrologists would lead to an overload of the nephrology care capacities. Large differences in estimated GFRs with different corrections for serum creatinine are observed, resulting in important CKD classification differences. Standardization of serum creatinine assays is mandatory before guidelines, and especially the routine provision of the estimated GFR by the abbreviated MDRD formula, can be implemented in clinical practice.

Adult↗
PubMed2005

Plasma N-terminal pro-brain natriuretic peptide concentration predicts coronary events in men at work: a report from the BELSTRESS study.

AIMS: Increased levels of neurohormonal markers, including the N-terminal fragment of pro-brain natriuretic peptide (NT-pro-BNP), have been shown to be of prognostic significance in patients with heart failure or coronary heart disease (CHD). The aim of this study was to study the predictive value of NT-pro-BNP for coronary events in a middle-aged population of men at work. METHODS AND RESULTS: A nested case-control study was performed in a large cohort of over 10 000 men at work (aged 35-59) after a median follow-up of 2.66 years. In total, 66 individuals who developed coronary events were matched on a 3-to-1 basis to 198 controls free of coronary events during follow-up. Besides clinical characteristics and conventional cardiac risk factors, NT-pro-BNP (electrochemiluminiscence assay, Roche diagnostics) and serum creatinine levels were determined. In univariable analysis, cases were more frequently current smokers and diabetics, had more frequently a history of CHD, and had higher levels of total cholesterol and systolic blood pressure (SBP), and lower levels of HDL cholesterol. A highly significant difference (P < 0.0001) was noted for NT-pro-BNP levels between cases (median 48.5 pg/mL, interquartile range 26.4-116.6 pg/mL) and controls (30.0 pg/mL, 19.5-47.6 pg/mL). In multivariable conditional logistic regression analysis, NT-pro-BNP remained strongly associated with risk for coronary events [third vs. first tertile, odds ratio (95% CI) 3.24 (1.18-8.85)], independent of body mass index, smoking, diabetes, SBP, total and HDL cholesterol, creatinine, and previous CHD. CONCLUSION: NT-pro-BNP is a strong predictor of coronary events in men at work after a relatively short period, even after adjustment for conventional risk factors.

Adult↗
PubMed2005

Subclinical iron deficiency is a strong predictor of bacterial vaginosis in early pregnancy.

BACKGROUND: Bacterial vaginosis (BV) is the single most common vaginal infection in women of childbearing age and associated with a sizeable infectious disease burden among both non-pregnant and pregnant women, including a significantly elevated risk of adverse pregnancy outcome. Overall, little progress has been made in identifying causal factors involved in BV acquisition and persistence. We sought to evaluate maternal iron status in early pregnancy as a putative risk factor for BV, considering that micronutrients, and iron deficiency in particular, affect the host response against bacterial colonization, even in the setting of mild micronutrient deficiencies. METHODS: In a nested case-control study, we compared maternal iron status at entry to prenatal care (mean gestational age 9.2 +/- 2.6 weeks) between eighty women with healthy vaginal microflora and eighteen women with vaginosis-like microflora. Vaginal microflora status was assessed by assigning a modified Nugent score to a Gram-stained vaginal smear. Maternal iron status was assayed by an array of conventional erythrocyte and serum indicators for iron status assessment, but also by more sensitive and more specific indicators of iron deficiency, including soluble transferrin receptors (sTfR) as an accurate measure of cellular and tissue iron deficiency and the iron deficiency log10[sTfR/ferritin] index as the presently most accurate measure of body storage iron available. RESULTS: We found no statistically significant correlation between vaginal microflora status and routinely assessed iron parameters. In contrast, a highly significant difference between the healthy and vaginosis-like microflora groups of women was shown in mean values of sTfR concentrations (1.15 +/- 0.30 mg/L versus 1.37 +/- 0.38 mg/L, p = 0.008) and in mean iron deficiency log10[sTfR/ferritin] index values (1.57 +/- 0.30 versus 1.08 +/- 0.56, p = 0.003), indicating a strong association between iron deficiency and vaginosis-like microflora. An sTfR concentration > 1.45 mg/L was associated with a 3-fold increased risk (95%CI: 1.4-6.7) of vaginosis-like microflora and after controlling for maternal age, gestational length, body mass, parity, and smoking habits with an adjusted odds ratio of 4.5 (95%CI: 1.4-14.2). CONCLUSION: We conclude that subclinical iron deficiency, presumably resulting from inadequate preconceptional iron supplies, is strongly and independently associated with vaginosis-like microflora during early pregnancy.

Adult↗
PubMed2005

Inflammatory markers in depressed post-myocardial infarction patients.

BACKGROUND: Depressive disorder in the post-myocardial infarction (MI) period has been associated with increased cardiac morbidity and mortality. Possible pathophysiological mechanisms behind this association are not clear. Major depression in physically healthy subjects has been related to immune abnormalities including increased plasma levels of interleukin-6 (IL-6), tumor necrosis factor alfa (TNF-alpha) and C-reactive protein (CRP). In patients with MI, increased inflammatory markers, such as CRP and TNF-alpha, have been associated with increased cardiovascular events. It was the aim of this study to test the hypothesis that depression in post-MI patients is associated with increased inflammation as compared to non-depressed post-MI patients. METHODS: The cytokines IL-6 and TNF-alpha ; the soluble cytokine receptors sIL-6R, sTNF-RI and sTNF-RII; neopterin; and the inflammation-sensitive plasma proteins (ISPs) CRP and haptoglobin were assessed in a group of 57 patients with a diagnosis of depression post-MI and in a control group of 46 non-depressed post-MI patients, matched for age, gender and time elapsed since MI. RESULTS: Cytokine, neopterin and ISP levels were not statistically different in the depressed post-MI group as compared to the non-depressed post-MI group. Several inflammatory markers were however elevated in both cohorts when compared with levels reported in healthy subjects, indicating persistent inflammation several months after MI. CONCLUSIONS: There was no indication of increased inflammation in depressed post-MI patients as compared to non-depressed post-MI patients.

Adult↗
PubMed2005

Associations between dimensions of job stress and biomarkers of inflammation and infection.

OBJECTIVE: The objective of this study was to examine associations between dimensions of job stress and indicators of chronic inflammation and infection. METHODS: Within a subsample from the BELSTRESS study of 892 male subjects free of cardiovascular disease, dimensions of job stress from the job demand-control-support model were related to biomarkers of inflammation (plasma fibrinogen concentrations, high-sensitivity C-reactive protein, and serum amyloid A) and infection (titers against Chlamydia pneumoniae, cytomegalovirus, and Helicobacter pylori). RESULTS: A negative association was found between job control and plasma fibrinogen concentration, independent from age, education, occupation, body mass index, smoking, alcohol consumption, and use of lipid-lowering and antihypertensive medication. Higher social support at work was independently related to an increased risk of positive titers against cytomegalovirus. CONCLUSIONS: Results confirm previous findings regarding elevated plasma fibrinogen and low job control.

Adult↗
PubMed2004

Cloning of 16S rRNA genes amplified from normal and disturbed vaginal microflora suggests a strong association between Atopobium vaginae, Gardnerella vaginalis and bacterial vaginosis.

BACKGROUND: The pathogenesis of bacterial vaginosis remains largely elusive, although some microorganisms, including Gardnerella vaginalis, are suspected of playing a role in the etiology of this disorder. Recently culture-independent analysis of microbial ecosystems has proven its efficacy in characterizing the diversity of bacterial populations. Here, we report on the results obtained by combining culture and PCR-based methods to characterize the normal and disturbed vaginal microflora. RESULTS: A total of 150 vaginal swab samples from healthy women (115 pregnant and 35 non-pregnant) were categorized on the basis of Gram stain of direct smear as grade I (n = 112), grade II (n = 26), grade III (n = 9) or grade IV (n = 3). The composition of the vaginal microbial community of eight of these vaginal swabs (three grade I, two grade II and three grade III), all from non-pregnant women, were studied by culture and by cloning of the 16S rRNA genes obtained after direct amplification. Forty-six cultured isolates were identified by tDNA-PCR, 854 cloned 16S rRNA gene fragments were analysed of which 156 by sequencing, yielding a total of 38 species, including 9 presumptively novel species with at least five species that have not been isolated previously from vaginal samples. Interestingly, cloning revealed that Atopobium vaginae was abundant in four out of the five non-grade I specimens. Finally, species specific PCR for A. vaginae and Gardnerella vaginalis pointed to a statistically significant co-occurrence of both species in the bacterial vaginosis samples. CONCLUSIONS: Although historically the literature regarding bacterial vaginosis has largely focused on G. vaginalis in particular, several findings of this study--like the abundance of A. vaginae in disturbed vaginal microflora and the presence of several novel species--indicate that much is to be learned about the composition of the vaginal microflora and its relation to the etiology of BV.

Actinobacteria↗
PubMed2004

Association of CD163+ macrophages and local production of soluble CD163 with decreased lymphocyte activation in spondylarthropathy synovitis.

OBJECTIVE: Since CD163+ macrophages are selectively increased in spondylarthropathy (SpA) synovitis, we investigated the role of CD163+ macrophages in synovial inflammation. METHODS: Synovial biopsy samples from 26 SpA and 23 rheumatoid arthritis (RA) patients were analyzed for macrophage and lymphocyte subsets. Synovial fluid (SF) samples were analyzed by Western blotting and enzyme-linked immunosorbent assay for soluble CD163 (sCD163) and by flow cytometry for lymphocyte activation. We also analyzed sCD163 in sera from 100 SpA patients, 23 RA patients, 20 healthy controls, and 20 SpA patients treated with infliximab. Polymorphism of haptoglobin (Hp), the CD163 ligand, was determined in 130 SpA and 23 RA patients. RESULTS: CD163+ macrophages, but not CD68+ macrophages, were significantly increased in SpA versus RA synovium and in HLA-B27+ versus HLA-B27- SpA. Despite similar lymphocyte numbers, activated lymphocytes (CD69+) were significantly decreased in SpA versus RA patients, with an inverse correlation between CD163 and CD69 levels. Local production of sCD163 was evidenced by a 5-7-fold higher level of sCD163 in SF than in serum and by the correlation with synovial lining CD163+ macrophages in SpA. SF sCD163 levels correlated directly with global inflammation but correlated inversely with CD69+ SF T lymphocytes in the synovium. In contrast, serum sCD163 levels were only moderately increased, did not correlate with SF sCD163 levels or parameters of inflammation, and were unaffected by infliximab therapy. The distribution of Hp polymorphism was not altered in SpA and was not related to CD163 expression. CONCLUSION: Increased numbers of CD163+ macrophages in SpA synovium and local production of sCD163 are associated with global inflammation as well as impairment of T cell activation, suggesting a dual role for CD163+ macrophages in SpA synovitis.

Adult↗
PubMed2004

Oxidized low-density lipoprotein, iron stores, and haptoglobin polymorphism.

BACKGROUND: In vitro experimental studies demonstrated that iron promotes free radical-induced low-density lipoprotein (LDL) oxidation. OBJECTIVE: To test the hypothesis that circulating oxidized LDL (oxLDL) levels might be associated with body iron stores (serum ferritin) and iron-related genetic markers (hemochromatosis gene C282Y mutation, haptoglobin polymorphism). METHODS: We investigated 381 (176 males, 205 females, age 45 +/- 6 years) healthy Caucasians. Serum oxLDL, assayed by a mAb-4E6-based enzyme-linked immunosorbent assay (ELISA), was expressed as oxLDL/LDL ratio to adjust for serum LDL-cholesterol concentration. Hemochromatosis gene C282Y mutation analysis was performed by a Taqman-based polymerase chain reaction (PCR) assay. Haptoglobin (Hp) phenotypes (Hp 1-1, Hp 2-1, Hp 2-2) were determined by starch gel electrophoresis. RESULTS: In stepwise multivariate regression analysis, gender (P < 0.0001), current smoking (P < 0.0001), HDL-cholesterol (P = 0.0001), ferritin (P = 0.0051), body mass index (BMI) (P = 0.0063), and Hp phenotype (P = 0.0331) independently predicted oxLDL/LDL ratio in the total group. In men, smoking (P < 0.0001), ferritin (P = 0.0052), Hp phenotype (P = 0.0063), and HDL-cholesterol (P = 0.0127) were independent determinants of oxLDL/LDL ratio. In women, only body mass index (P < 0.0001), HDL-cholesterol (P = 0.0005), and smoking (P = 0.0025) were significantly associated with oxLDL/LDL ratio. The C282Y mutation (wild-type versus C282Y heterozygotes) was not associated with oxLDL/LDL ratio in both sexes. CONCLUSION: Serum ferritin concentration and Hp polymorphism are independently associated with circulating oxLDL levels in males.

Adult↗
PubMed2004

Noninvasive diagnosis of liver cirrhosis using DNA sequencer-based total serum protein glycomics.

We applied our 'clinical glycomics' technology, based on DNA sequencer/fragment analyzers, to generate profiles of serum protein N-glycans of liver disease patients. This technology yielded a biomarker that distinguished compensated cirrhotic from noncirrhotic chronic liver disease patients, with 79% sensitivity and 86% specificity (100% sensitivity and specificity for decompensated cirrhosis). In combination with the clinical chemistry-based Fibrotest biomarker, compensated cirrhosis was detected with 100% specificity and 75% sensitivity. The current 'gold standard' for liver cirrhosis detection is an invasive, costly, often painful liver biopsy. Consequently, the highly specific set of biomarkers presented could obviate biopsy in many cirrhosis patients. This biomarker combination could eventually be used in follow-up examinations of chronic liver disease patients, to yield a warning that cirrhosis has developed and that the risk of complications (such as hepatocellular carcinoma) has increased considerably. Our clinical glycomics technique can easily be implemented in existing molecular diagnostics laboratories.

Blood Proteins↗
PubMed2004

What exactly was wrong with the Trilucent breast implants? A unifying hypothesis.

Trilucent soybean oil-filled breast implants were initially announced as the ultimate prostheses for breast augmentation. However, after an increasing number of reports of local complications and hazardous metabolites attributable to lipid oxidation, first the United Kingdom Medical Devices Agency and later the Belgian National Ministry of Health urged all plastic surgeons to contact their patients and advise them to have the implants removed and, if desired, replaced with another type of prosthesis. In our plastic surgery department, 13 patients received bilateral implants with triglyceride-filled prostheses between February and July of 1996, for primary breast augmentation or replacement of previously implanted prostheses. For 12 of those 13 patients, the prostheses have been explanted, because of unilateral breast enlargement attributable to a ruptured prosthesis for five patients and following the recommendation of the Belgian National Ministry of Health for the other seven patients. Before explantation, all patients underwent standard clinical examinations, with assessments of breast shape, volume, and firmness. Blood analyses were performed, with a special focus on liver enzymes, as were urinalyses. Magnetic resonance imaging scans were obtained before explantation; for two patients, the scans revealed a fluid level separating two liquid layers in an intact prosthesis. This is the first report of such a finding. The removed implants were examined for any damage or shell deterioration and for changes in color and viscosity, the weights and volumes were measured and compared with the initial values for the implanted prostheses, and complete biochemical analyses of the accumulated fluid in cases of ruptured prostheses and of the filler material in cases of intact prostheses were performed. This small but well-documented series illustrates the multitude of problems associated with triglyceride-filled implants, including bleeding of the triglyceride filler; shell deterioration, as indicated by a loss of texture and extreme fragility of the implant (with rupture or delamination with a simple finger touch); an increase in osmotic pressure exerted by the degraded filler material; progressive weakening of the outer silicone shell, with influx of plasma proteins of up to 750 kDa, eventually resulting in rupture of the prosthesis; a lack of oxidative stability and the formation of toxic oxidation products; a lack of biocompatibility, with the formation of insoluble organic soap-like material; and a pronounced inflammatory reaction. It is concluded that the sequential and/or simultaneous occurrence of (1) implant bleeding, (2) lipid infiltration of the silicone elastomer, and (3) inflammation attributable to oxidation products provides an overall explanation or unifying hypothesis for the wide variety of adverse events related to soybean oil-filled implants.

Biocompatible Materials↗
PubMed2003

Improvement of cyclosporin A determination in whole blood by reversed-phase high-performance liquid chromatography.

A chromatographic method was developed for the determination of cyclosporin A in human whole blood using reversed-phase HPLC at room temperature. Most previous reports carried out this liquid chromatographic separation at temperatures above 70 degrees C. The present procedure greatly improves the detection limit by controlling peak broadening effects, as well as the lifetime of the column at room temperature. Under optimal conditions and using ketoconazole as an internal standard, the calibration graph was linear in the range of 16-1000 microg/L with a relative standard deviation of 3.72% at 150 microg/L and 2.45% at 300 microg/L (n = 11) of cyclosporin A. The detection limit was of 5.0 microg/L cyclosporin A. By this procedure, cyclosporin A pharmacokinetic parameters in healthy Chinese subjects were studied. The developed method could be applied to the quantification of cyclosporin A in human blood samples and allows the study of its pharmacokinetics in routine laboratories.

Chromatography, High Pressure Liquid↗