Search PubMed⌕ Search

Biomedical subjects

R Schepers

Publications and source records attributed to R Schepers.

17 recordsLinked to original sources
PubMed2001

Correlation of mycophenolic acid pharmacokinetic parameters with side effects in kidney transplant patients treated with mycophenolate mofetil.

BACKGROUND: Mycophenolate mofetil (MMF) is widely used in organ transplantation to prevent acute rejection. Because MMF can produce hematologic and/or gastrointestinal toxicity, therapeutic monitoring is becoming mandatory. This study was designed to investigate the relationship between the clinical events and the pharmacokinetics of mycophenolic acid (MPA) in adult renal transplantation. METHODS: Thirty-one adult kidney recipients were prospectively included in the study. MPA pharmacokinetic profiles (blood sampling at 0, 0.5, 1, 2, 4, 6, and 12 h after MMF oral dose) were obtained after transplantation (desired creatinine clearance, 40 mL/min), at 3 months after grafting, and at every clinical event (e.g., side effect or rejection). All patients received a 10-day course of anti-thymocyte globulin, cyclosporine, MMF (1 g twice daily), and steroids. RESULTS: We divided the 31 patients into two groups (groups 1 and 2). Ten patients (32%; group 1) had uneventful outcomes, and 21 patients (68%; group 2) presented with MPA-related side effects. For groups 1 and 2, the MPA trough concentrations (C(min)) were 1.63 +/- 1.07 and 2.29 +/- 1.16 mg/L, respectively (P = 0.06), and the areas under the curve (AUCs) for MPA from t(0) to t(12 h) (MPA-AUC(0-12h)) were 39.80 +/- 15.29 and 62.10 +/- 21.07 mg. h/L, respectively (P = 0.0005, two-sample t-test). Three patients experienced acute graft rejection after the oral MMF dose was reduced because of side effects. In this group, the MPA-C(min) and MPA-AUC were significantly lower by the time acute rejection occurred (1.00 +/- 0.45 mg/L and 25.00 +/- 6.20 mg. h/L, respectively). At a fixed dose (1 g twice per day), we compared the pharmacokinetic parameters of MPA [C(min), the MPA concentration 30 min after the oral dose of MMF (C(30)), and AUC] according to the presence or absence of side effects in the two groups. C:(min) and AUC did not differ between the two groups [C(min) = 2.22 +/- 1.13 vs 2.17 +/- 1.13 mg/L (P = 0.9); AUC = 66.82 +/- 29.87 vs 55.70 +/- 11.74 mg. h/L (P = 0.11)]; and C(30) was significantly higher in group 2 than in group 1 (C(30) = 32.99 +/- 12.59 vs 7.45 +/- 5.40 mg/L; P <0.0001). CONCLUSIONS: Our results demonstrate a pharmacokinetic/pharmacodynamic relationship between MPA and clinical events. At a fixed dose of 2 g/day, a high C(30) is associated with increased risk for side effects. This study suggests that dividing the MMF daily oral dose into more than two divided doses might prevent early MPA toxicity.

Adolescent↗
PubMed2001

Pharmacokinetic basis for the efficient and safe use of low-dose mycophenolate mofetil in combination with tacrolimus in kidney transplantation.

BACKGROUND: Mycophenolate mofetil (MMF) is an effective posttransplantation immunosuppressive agent used in combination with cyclosporin A (CsA) or tacrolimus (Tc). An increase in plasma mycophenolic acid (MPA) has been shown in patients receiving Tc-MMF combination therapy compared with CsA-MMF combination therapy at the same dose of MMF. The aim of this prospective study was to assess the pharmacokinetic/pharmacodynamic (PK/PD) relationship for MPA in kidney transplant patients receiving low-dose MMF (500 mg twice a day) in combination with Tc. METHODS: Adult kidney transplant recipients (n = 51) were included. MPA-PK profiles (blood sampling at 0, 0.5, 1, 2, 4, 6, and 12 h after MMF oral dose) were obtained within the first 2 weeks after transplantation, 3 months after grafting, and at every adverse clinical event [side effect or acute rejection (AR)]. All patients received Tc, MMF (500 mg twice a day), and steroids. RESULTS: Thirty patients (59%) had uneventful outcomes, and 21 patients had 33 episodes of MPA-related side effects; only 3 patients had AR. A total of 78 MPA-PK profiles were obtained. The following PK parameters were increased in the side-effects group compared with the non-side effects group: mean MPA c(min), 2.63 +/- 1.58 vs 1.75 +/- 0.82 mg/L (P = 0.016); mean c(30), 10.47 +/- 6.27 vs 7.66 +/- 8.95 mg/L (P = 0.009); mean c(60), 9.67 +/- 5.42 vs 5.83 +/- 2.6 mg/L (P = 0.0002); mean area under the MPA time-concentration curve from 0 to 12 h [MPA-AUC((0-12))], 48.38 +/- 18.5 vs 36.04 +/- 10.82 mg. h/L (P = 0.0006); mean dose-normalized MPA-AUC, 0.16 +/- 0.05 vs 0.12 +/- 0.04 (mg. h/L)/(mg/m(2)) (P = 0.0015). For the three AR patients, MPA concentrations obtained at the time of AR revealed MPA c(min) values of 1.86, 1.76, and 3.83 mg/L, respectively, and MPA-AUC((0-12)) values of 37.7, 24.9, and 104.9 mg. h/L. The threshold of toxicity was 3 mg/L (sensitivity, 38.7%; specificity, 91.5%) for c(min), 8.09 mg/L for maximum MPA concentration during the first hour (sensitivity, 77.8%; specificity, 67.4%), and 37.6 mg. h/L for MPA-AUC((0-12)) (sensitivity, 83.3%; specificity, 59.6%). CONCLUSIONS: These results demonstrate the relationship between plasma MPA concentrations and toxicity. High c(min), c(30), and c(60) values as well as AUC((0-12)) are associated with increased risk for side effects. These values may have an importance in a routine monitoring program.

Adult↗
PubMed2000

Psychosomatic symptoms and breathing pattern.

OBJECTIVE: Study of the links between breathing pattern, negative affectivity, and psychosomatic complaints at rest and following hyperventilation. METHODS: In 819 patients with anxiety and somatoform disorders and 159 healthy subjects, self-reported symptoms, breathing pattern, and end-tidal CO(2) concentration (FetCO(2)) were recorded during rest and following a hyperventilation provocation test (HVPT). The relationship between disorder category, symptoms, age, and score of STAI-trait (as a measure of negative affectivity) on the one hand, and breathing pattern on the other was investigated, separately in men and women. RESULTS: Anxiety disorders, and to a lesser extent, somatoform disorders, were characterized by breathing instability (progressive decrease of FetCO(2) at rest during mouthpiece breathing, delayed recovery of FetCO(2) following HVPT), the mean values of respiratory frequency, and FetCO(2) being modulated by STAI-trait. After grouping the symptoms into independent factors, links were observed between symptoms and breathing pattern, independently from the presence of an anxiety or somatoform disorder. CONCLUSION: Some symptom factors appeared to be related to a lower FetCO(2) during hyperventilation, others likely directly influenced the breathing pattern. Among those, mainly respiratory symptoms were accompanied by a reduction of FetCO(2) at rest, with slower recovery of FetCO(2) following HVPT. The latter was observed also in the presence of marked anxiety. In contrast, subjects complaining of dizziness, fainting, and paresthesias in daily life presented higher values of FetCO(2) following HVPT, probably due to a voluntary braking of ventilation during HVPT.

Adult↗
PubMed1999

Physical performance of patients with numerous psychosomatic complaints suggestive of hyperventilation.

In some patients exercise induces numerous complaints which cannot be attributed to an organic disorder, and which are suggestive of hyperventilation. The study was designed to investigate in this type of patient: 1) exercise capacity and muscle force; 2) breathing pattern and symptoms during maximal exercise and recovery; 3) relationships between symptoms and breathing pattern. Twenty-four patients were compared with 20 healthy subjects. They performed a maximal incremental cycle ergometer test and peripheral and respiratory muscle strength were measured. Patients tended to have a decreased exercise capacity and presented with moderately reduced muscle strength. At comparable minute ventilation, breathing frequency was higher (mean: 24 versus 21 per minute) and tidal volume smaller (mean: 1.42 versus 1.67 L). End-tidal partial pressure of carbon dioxide (PET,CO2) was not significantly different. A significant relation was observed between PET,CO2 and respiratory frequency during recovery in patients, suggesting a reduced flexibility of the ventilatory response to exercise. In patients respiratory complaints and paresthesias were weakly correlated to PET,CO2 at moderate exercise. It is suggested that the physical deconditioning observed in those patients is rather a consequence than a cause of the response to exercise. The link between symptoms and breathing pattern might be explained by a psychological conditioning process.

Adult↗
PubMed1998

Subjective symptoms and breathing pattern at rest and following hyperventilation in anxiety and somatoform disorders.

The purpose of the present study was to investigate the diagnostic specificity of bodily symptoms and respiratory behavior at rest and after a hyperventilation provocation test (HVPT) in patients that were either grouped according to the DSM classification or diagnosed as suffering from hyperventilation syndrome. Nine hundred three anxiety and somatoform patients, showing symptoms supposedly caused by psychogenic hyperventilation, and 170 healthy subjects, were studied. Breathing pattern and end-tidal CO2 concentration were recorded during breathing at rest and following a HVPT. Subjective symptoms in daily life and after HVPT were measured. A principal-components analysis was performed on both the symptoms and breathing variables and their specificity levels were compared in the two classifications of patients. Some symptoms in daily life were grouped together with the same symptoms after the HVPT, other symptoms were not. This suggests that the HVPT elicited partly specific symptoms, and partly reproduced the symptoms experienced in daily life. Similar findings were observed with respect to the breathing variables. Patients with panic differed from other patients with anxiety disorders by an increased level of symptoms and a FETCO2 decline at rest. The HVPT may be informative for diagnosis because it provokes some of the typical somatic and psychological symptoms, and it identifies the breathing instability that is characteristic of both patients with HVS and with anxiety. The same symptoms and breathing variables characterized the patients, whatever their classification. Overall, the specificity of breathing variables is rather low.

Adult↗
PubMed1998

Comparative perspectives on doctors in management in the UK and The Netherlands.

The role of doctors in hospitals continues to change due to both external (policy) and internal (organisational change) pressures. Comparisons between The Netherlands and the UK highlight that several models of medical management are formulated and exist alongside each other, leading to more flexibility in the roles of both doctors and managers. In particular, the agendas concerning the quality of clinical care and cost-effectiveness are converging, emphasising the increasingly important role of medical managers.

Decision Making, Organizational↗
PubMed1997

Liquid chromatographic analysis of a formulation containing polymyxin, gramicidin and neomycin.

The development of a liquid chromatographic essay system for the stability study of a formulation containing polymyxin, gramicidin and neomycin is described. For the determination of each group of antibiotics, poly(styrenedivinylbenzene) is used as the stationary phase. The mobile phase for the determination of polymyxin consists of an aqueous solution containing 7 g l-1 of sodium sulfate, 50 ml l-1 of 1 M phosphoric acid and 160 ml l-1 of acetonitrile. UV detection is performed at 215 nm. An aqueous solution containing 70 g l-1 of sodium sulfate, 1.4 g l-1 of sodium octanesulfonate and 50 ml l-1 of 0.2 M phosphate buffer pH 3.0 is used as the mobile phase for the determination of neomycin. Since neomycin has no UV-absorbing chromophore, pulsed electrochemical detection is chosen to determine neomycin. For each method, the influence of the different chromatographic parameters on the separation, the selectivity towards the other active compounds and the excipients, the repeatability and the linearity were investigated. The stability of the formulation was examined at 0, 6 and 12 months.

Anti-Bacterial Agents↗
PubMed1997

Unsteadiness of breathing in patients with hyperventilation syndrome and anxiety disorders.

The breathing pattern of 399 patients with hyperventilation syndrome (HVS) and/or with anxiety disorders and that of 347 normal controls was investigated during a 5 min period of quiet breathing and after a 3 min period of voluntary hyperventilation. The diagnosis of HVS was based on the presence of several suggestive complaints occurring in the context of stress, and reproduced by voluntary hyperventilation. Organic diseases as a cause of the symptoms were excluded. The anxiety disorders were diagnosed by means of an abbreviated version of the Anxiety Disorders Interview Schedule (ADIS). There was a large overlap between the two diagnoses. Simply breathing via a mouthpiece and pneumotachograph made end-tidal CO2 fractional concentration (FET,CO2) decrease progressively both in hyperventilators and in patients with anxiety disorders, but not in normals. At the start of the measurement the FET,CO2 was not different between patients and healthy subjects. In patients < or = 28 yrs, the decrease of FET,CO2 resulted from a higher tidal volume, and in patients > or = 29 years from an increase in frequency. After voluntary hyperventilation, the recovery of FET,CO2, was delayed in patients, due to a slower normalization of respiratory frequency in females and in older males, and of tidal volume in younger males, and also due to less frequent end-expiratory pauses. When breathing was recorded first by means of inductive plethysmography (Respitrace), the progressive decline of FET,CO2 seen in patients was not observed: from the onset of the recording, FET,CO2 was reduced in patients. It did not change further when, immediately afterwards, the subject switched to mouthpiece breathing. The finding that breathing through a mouthpiece induces hyperventilation in patients and that recovery of FET,CO2 is delayed after voluntary hyperventilation, suggests that the respiratory control system is less resistant to challenges (mouthpiece or voluntary hyperventilation) in those patients. On the other hand, the lower values of FET,CO2 measured during recording by means of a Respitrace probably result from a challenge, prior to the recordings, induced by the fitting of the measuring device to the patient. This unsteadiness of breathing characterizes patients with hyperventilation syndrome and those with anxiety disorders, but is not sufficiently sensitive to be used for individual diagnosis.

Adult↗
PubMed1996

Determination of neomycin sulfate by liquid chromatography with pulsed electrochemical detection.

The determination of neomycin sulfate by liquid chromatography using a column packed with a poly(styrenedivinylbenzene) co-polymer and pulsed electrochemical detection on a gold electrode is described. The mobile phase consisted of an aqueous solution containing 70 g/l of sodium sulfate, 1.4 g/l of sodium 1-octanesulfonate and 50 ml/l of a 0.2 M phosphate buffer (pH 3.0). Sodium hydroxide was added post-column. The influence of the different chromatographic parameters on the separation was investigated. The method shows good linearity and repeatability and is stability indicating. A number of commercial samples was analyzed using this method and the results were compared with results obtained with the European Pharmacopoeia method and a previously described thin-layer chromatographic method.

Anti-Bacterial Agents↗
PubMed1996

Total respiratory impedance measured by means of the forced oscillation technique in subjects with and without respiratory complaints.

The purpose of this study was to determine whether the forced oscillation technique is more sensitive than spirometry to detect lung function alterations in subjects with respiratory complaints. The input impedance of the respiratory system (between 2 and 24 Hz) and maximal expiratory flows and volumes were measured in 1,255 subjects referred for routine spirometry. A questionnaire concerning respiratory complaints was administered. A discriminant analysis was performed between subgroups of subjects without (137 males and 140 females), with moderate (115 males and 109 females) and with marked respiratory complaints (149 males and 132 females). A clear-cut separation was achieved by this analysis only between those subjects without and with marked complaints. Both lung volumes and flows as well as impedance parameters (mean value and frequency dependence of resistance in females, mean resistance in males) contributed to the discrimination of subjects without and with marked respiratory complaints, although there was only a moderate decrease of discriminative power when the impedance parameters were excluded. The contribution of the forced oscillation parameters to discriminative power was larger in females than in males (40 vs 19%), which may be related to the higher prevalence of asthma in our population of females. Excluding the subjects with marked functional impairment improved the share of forced oscillation parameters only slightly with respect to lung volumes and flows (females 54 vs males 23%). Considered separately, however, the sensitivity of spirometry and forced oscillation technique to detect symptomatic people appeared to be similar. We conclude that impedance measurements by forced oscillation technique and routine spirometry are both associated with respiratory complaints. Our results indicate that the information provided by impedance measurements can be complimentary to that obtained by spirometric indices.

Adult↗
PubMed1985

[Not Available].

Explore the source record for details and available documents.

Academies and Institutes↗
PubMed1985

[Not Available].

Explore the source record for details and available documents.

Academies and Institutes↗
PubMed1984

Pulmonary resistance and compliance by auto- and cross-correlation functions of transpulmonary pressure and flow.

A technique is described on how to calculate the pulmonary resistance and compliance from the higher order harmonics present in mouth flow and transpulmonary pressure signals during spontaneous breathing. The estimates of resistance and compliance (or rather reactance) obtained from these harmonics following a conventional Fourier transform are not reliable because of a lack of reproducibility. This is obviated by a preliminary smoothing of the signals by means of auto- and cross-correlation functions. Both the conventional and the modified technique yield identical results for the fundamental component of breathing.

Adolescent↗
PubMed1976

Respiratory failure: correlation between encephalopathy, blood gases and blood ammonia.

In 59 patients with respiratory insufficiency due to chronic obstructive pulmonary disease (COPD) the relationship between the state of consciousness, the blood gases and blood ammonia were studied. Interindividually, a significant correlation was found between the encephalopathy and SaO2, PaCO2 or ammonia, and also between the blood gases and ammonia. On the other hand, an intraindividual study, performed on patients with minor cerebral dysfunction, showed that only PaCO2 was significantly correlated with the stage of consciousness. Ammonia did not appear to have a neurotoxic influence. The ammonia level seemed to be influenced primarily by other factors than the blood gases, although there was a borderline influence of SaO2 on aterial ammonia and a significant influence of PaCO2-HCO3 and pH on venous ammonia.

Adult↗