Biomedical subjects

M Kraemer

Publications and source records attributed to M Kraemer.

At least 19 recordsLinked to original sources

PubMed2006

A new model for the determination of fluid status and body composition from bioimpedance measurements.

In patients with end stage renal failure, control of the fluid status of the body is lost and fluid accumulates continuously. By dialysis therapy, excess fluid can be removed, but there are no reliable methods to establish the amount of excess fluid to be removed. Severe and even lethal complications may be the consequence of longer term deviations from a normal fluid status in dialysis patients, but also in other patient groups. Therefore, a large medical need exists for a precise and pragmatic method to determine fluid status. Bioimpedance measurement, today mainly used for nutrition status assessment, is regarded as an interesting candidate method for fluid status determination. This paper presents a four-compartment model of the human body, developed to derive information on fluid status from extra- and intracellular volumes measured by bioimpedance spectroscopy. The model allows us to determine weights of each of four compartments (overhydration, fat, muscle and remaining 'basic' components) by analyzing extra- and intracellular water volumes in different tissues of the body. Thereby fluid status (overhydration volume, normohydrated weight of the patient) as well as nutrition and fitness status (lean body, fat and muscle mass) can be determined quantitatively from a single measurement. A preliminary evaluation of the performance of a system consisting of a bioimpedance spectrum analyzer and the four-compartment model is also provided.

Adult↗

PubMed2006

Detection limit of methods to assess fluid status changes in dialysis patients.

Technical systems for an accurate and practicable fluid management of dialysis patients are urgently needed, since current clinical methods are partially subjective, imprecise, and time consuming. Such new systems should not only allow the determination of the target normohydration weight, but also must be able to detect clinically relevant changes in fluid volume ( approximately 1 l). This study focuses on the systematic analysis of the detection limit of several candidate methods for fluid management. In a cohort of 16 new dialysis patients, several candidate methods were applied in parallel during each treatment of the initial weight reduction phase: the measurement of vena cava diameter (VCD), vena cava collapsibility index (CI), the blood volume drop during an ultrafiltration (UF) bolus (Deltarelative blood volume (RBV)-), the rebound after the UF bolus (DeltaRBV+), and the extracellular fluid volume determined with whole body bioimpedance spectroscopy (BIS). A clinical reference method was used to manage the fluid status of patients. All methods showed significant correlations with predialysis weight. The detection limits W(lim) of candidate methods for changes in fluid status were assessed as W(lim)=0.87 kg+/-0.64 kg (BIS), 1.74 kg+/-1.56 kg (VCD), 2.3 kg+/-1.0 kg (DeltaRBV-), 7.4 kg+/-8.5 kg (CI), 40 kg+/-108 kg (DeltaRBV+). Only BIS shows a satisfactorily low detection limit W(lim), whereas W(lim) was rated as critical for the VCD and DeltaRBV- methods, and as unacceptable for the CI and DeltaRBV+ methods. Bioimpedance spectroscopy appears to be the most promising method for a practical fluid management system in dialysis.

Adult↗

PubMed2005

Suppression of MR gradient artefacts on electrophysiological signals based on an adaptive real-time filter with LMS coefficient updates.

Electrocardiogram (ECG) acquisition is still a challenge as gradient artefacts superimposed on the electrophysiological signal can only be partially removed. The signal shape of theses artefacts can be similar to the QRS-complex, causing possible misinterpretation during patient monitoring and false triggering/gating of the MRI. For their real-time suppression, an adaptive filter is proposed. The adaptive filter is based on the noise-canceller configuration with LMS coefficient updates. The references of the noise canceller are the three gradient signals that are acquired simultaneously with the noisy ECG. Tests were done on patients, on volunteers and using an MR-safe ECG simulator. The noise canceller's performance was measured offline, simulating real-time processing by point-by-point operations. To create worst-case scenarios, clinical sequences with strong- and fast-switching gradients have been chosen. The noise-cancelling filter reduces the gradient artefacts' peak amplitudes by 80-99% after adaptation, without changing the desired ECG signal shape. The estimated reduction of total average power of the MR gradient artefacts is 62-98%. The proposed filter is capable of reducing artefacts due to strong- and fast-switching gradients in real-time applications and worst-case situations. The quality of the ECG is sufficiently high that a standard one-lead QRS-detector can be used for gating/triggering the MRI. For permanent patient monitoring, further improvements are needed.

Algorithms↗

PubMed2004

Subnormal visual acuity (SVAS) and albinism in Mexican 12-13-year-old children.

BACKGROUND: In a previous study the vision of 1046 12-13-year-olds in Sweden was examined. Of those 67 had some kind of visual disturbances and in 20 no obvious cause was found. In this group, defined as children with subnormal visual acuity syndromes (SVAS), albinism was shown to be a major cause to the visual dysfunction giving a prevalence of about 1%. This is about 100 times higher than previous figures. Albinism can therefore be the cause in many cases of unexplained low visual acuity, at least in Sweden. Subnormal visual acuity is usually found in 2-4% in a pediatric population and is often called 'amblyopia'. The Swedish study showed that in many cases 'amblyopia' should be replaced by 'SVAS' and further investigation. The present Mexican study was designed identically to the Swedish study. The objective was to describe the distribution of visual acuity and the prevalence of ocular disorders, including incidence of subnormal visual acuity (SVAS) and the occurrence of albinism in a Mexican population of 12-13-year-olds. SUBJECTS AND METHODS: Altogether 1035 children, 12-13 years of age, were examined. A total number of 344 children were referred to the university pediatric eye clinic for further examination. 272 of these had simple refractive errors, 59 were diagnosed with an ophthalmological disorder and 13 children could not be pathologically classified. These were referred to a second ophthalmological examination, including VEP (Visual Evoked Potential) recordings. VEP reveals an asymmetric (right vs. left) cortical response after monocular stimulation in albinism. RESULTS: No child showed iris translucency or any other typical albinoic sign. VEP was recorded from 11 children. Three children showed an asymmetric VEP and were classified as albinos. The VEP response was normal in 8 of the children. CONCLUSIONS: The results indicate that albinism is common in Mexico, although not as common as in a similar Swedish population. A prevalence of albinism of approximately 0.3% was found in the Mexican population, compared to approximately 1% in the Swedish study group. The number of albinos was much higher in both study groups than to be expected from previous estimates. The difference between the Swedish and the Mexican figures may be explained by the general difference in pigmentation between Sweden and Mexico and thus probably by the subsequent lower number of commonly occurring albino foci in the Mexican heritage. It is emphasised that in investigations of children with SVAS, also in countries with a generally high pigmentation level, electro-physiological examinations are important, to be able to reveal albinism, but also to exclude or verify other conditions in the SVAS group, for example neurometabolic conditions.

Adolescent↗

PubMed2004

Growth inhibition of MCF-7 tumor cell line by phenylacetate linked to functionalized dextran.

We investigated the antiproliferative effect of phenylacetate covalently linked to dextran derivatives (DMCBPA conjugates) on human breast cancer MCF-7 cells. We show that free sodium phenylacetate (NaPA) inhibits the cell growth (IC50 = 14 mM), while an important inhibitory effect is observed for DMCBPA conjugates. The IC50 dose of these conjugates is as low as 1.0 mg/ml, corresponding to 1.3 mM of phenylacetate. The precursors, dextran substituted with methylcarboxylate and benzylamide groups, did not affect the growth of MCF-7 tumor cells. We have observed that MCF-7 cell growth inhibition depends on amount of phenylacetate linked to the conjugate. The data indicated that an optimum antiproliferative effect is more significant when the amount of phenylacetate groups present on the dextran backbone is high. Analysis of doubling time by growth kinetics study shows that conjugates have more time-sustained effect than free NaPA. It is noteworthy that the inhibitory effect is observed at non-toxic concentration. Theses conjugates could be considered as acceptable derivatives to prevent tumor progression.

Antimetabolites, Antineoplastic↗

PubMed2003

Carboxymethyl benzylamide dextran inhibits angiogenesis and growth of VEGF-overexpressing human epidermoid carcinoma xenograft in nude mice.

Vascular endothelial growth factor (VEGF) expression is elevated in a wide variety of solid tumours. Inhibition of VEGF activities is able to reduce angiogenesis and tumour growth. We have recently shown in vitro that carboxymethyl dextran benzylamide (CMDB7) prevents the binding of VEGF(165) to its cell surface receptors and thus inhibits VEGF activities on endothelial cells. In the present study, we explored the effects of CMDB7 on highly aggressive human epidermoid carcinoma A431 cells known to overexpress epidermal growth factor receptors (EGFRs) and produce a high amount of VEGF and a minor quantity of bFGF. In vitro, CMDB7 blocked the mitogenic activity of A431-conditioned medium on endothelial cells. Concerning A431 cells, CMDB7 inhibited their proliferation and the VEGF(165) binding to them. In vivo, administration of CMDB7 (10 mg kg(-1)) three times per week for 2 weeks inhibited the growth of A431 xenografts in nude mice by 73% as compared to the control group. Immunostaining of endothelial cells with mouse-specific GSL-1 lectin in tumour sections revealed that CMDB7 also inhibited the density of intratumour endothelial cells by 66%. These findings demonstrate that CMDB7 has an efficient antiangiogenic and antitumour action in vivo even when tumour cells produce a high level of VEGF and EGFRs.

Animals↗

PubMed2003

Inhibition of epidermoid carcinoma A431 cell growth and angiogenesis in nude mice by early and late treatment with a novel dextran derivative.

We investigated the effect of a new dextran derivative, phenylacetate carboxymethyl benzylamide dextran (NaPaC), on epidermoid carcinoma A431 cells secreting a large quantity of angiogenic factor, vascular endothelial growth factor (VEGF). In vitro, NaPaC inhibited the proliferation of A431 cells (IC(50)=5 micro M). Also, NaPaC decreased the binding of radiolabelled VEGF(165) to endothelial cells (IC(50)=0.2 micro M). In vivo, we explored the effects of NaPaC (15 mg kg(-1)) on A431 xenograft growth starting the drug administration at the time of tumour cell inoculation (early treatment) and 1 week later, when tumours were well established (late treatment). Early treatment was more efficient on tumour inhibition (70% vs control) than late treatment (50% vs control). Early and late NaPaC-treatment increased the aponecrosis in tumour by 70 and 30%, respectively. Whatever treatment, NaPaC inhibited the intratumour endothelial cell density in the same manner. In contrast, vessel area was decreased only when NaPaC was injected early (35%). These results show that NaPaC has a potent inhibitory effect, dependent on treatment outset, on epidermoid carcinoma growth associated with an intratumour microvascular network diminution and an aponecrosis increase. As this drug is nontoxic at efficient dose, it offers interesting perspectives for the therapy of malignant lesions.

Animals↗

PubMed2003

Transfer into a mesothelioma cell line of tumor suppressor gene p16 by cholesterol-based cationic lipids.

In this work, the tumor suppressor gene p16 was efficiently transferred into FR cells isolated from a patient with malignant mesothelioma using cationic liposomes prepared from trimethyl aminoethane carbamoyl cholesterol (TMAEC-Chol) and triethyl aminopropane carbamoyl cholesterol (TEAPC-Chol). This transfer was performed after preliminary assays were undertaken to find the optimal transfection conditions. Results showed that an efficient transfer of plasmids containing the reporter gene pCMV-beta galactosidase vectorized by TMAEC-Chol/DOPE and TEAPC-Chol/DOPE liposomes into mesothelioma FR cells was obtained as assessed by luminometric measurements of beta-galactosidase activity. Cytotoxicity studied by MTT test showed that at concentrations used for this study, the cationic liposomes have no effect on cell growth. Transfer into mesothelioma FR cells of a plasmid construct containing the tumor suppressor gene p16 was carried out with these liposomes. Western blotting and immunofluorescence showed the presence of p16 in treated cells. An inhibition of cell growth was observed, indicating that efficient tumor suppressor gene transfer can be performed by using cationic liposomes.

Cell Division↗

PubMed2003

Spatial organization of three-dimensional cocultures of adriamycin-sensitive and -resistant human breast cancer MCF-7 cells.

Genetic and cellular heterogeneity is one of mechanisms involved in increasing tumour aggressiveness during neoplastic progression. Development of drug-resistant tumour cell subpopulations is a major problem in clinical oncology. Multi-drug resistant tumour cells survive when exposed to cytotoxic agents. Here, we studied in a three-dimensional (3D) coculture system, called "ex vivo nodules", how drug-resistant and sensitive tumour cells settle down in a 3D space. For this, we cocultured adriamycin-sensitive (MCF-7S) and -resistant (MCF-7R) human breast cancer cells in long term nodules. We showed that both types of cells are able to grow separately or in coculture until five weeks in spheroidal forms. MCF-7R cells did not loose their multi-drug resistance when cultured in nodules as measured by RT-PCR. Curiously, the exterior aspects of mixed (MCF-7S/ MCF-7R) nodules and MCF-7R nodules were similar whereas MCF-7S nodules were completely different. Nevertheless, morphologically these three nodule types were distinct, in particular in their density. Immunostaining showed that in mixed nodules, MCF-7R cells were arranged at the periphery, whereas the MCF-7S cells are in the central part of the nodules. Even if the mechanism of this arrangement remained unclear, this work shows that three-dimensional cell culture is well adapted to the study of the relationships between adhesion mechanisms and drug-resistance.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed2003

Clinical extracorporeal hybrid liver support--phase I study with primary porcine liver cells.

The objective of this study was to evaluate the feasibility and safety of a hybrid liver support system with extracorporeal plasma separation and bioreactor perfusion in patients with acute liver failure (ALF) who had already fulfilled the criteria for high urgency liver transplantation (LTx). Eight patients (one male, seven female) were treated in terms of bridging to transplantation. The mean age was 36.5 yr (range 20 to 58). Etiology of liver failure was drug-related in two patients, hepatitis B infection in three patients, and unknown for three patients. The bioreactors were charged with primary liver cells from specific pathogen-free pigs. Cell viability varied between 91 and 98%. Continuous liver support treatment over a period of 8 to 46 h (mean 27.3 h) was safely performed and well-tolerated by all patients. No complications associated with the therapy were observed during the follow-up period. Thrombocytopenia was considered to be an effect of the plasma separation. Subsequently, all patients were transplanted successfully and were observed over at least 3 yr with an organ and patient survival rate of 100%. Screening of patient's sera for antibodies specific for porcine endogenous retroviruses (PERVs) showed no reactivity--either prior to application of the system, or after extracorporeal treatment. The results encourage us to continue the development of the technology, and further studies appear to be justified. The bioreactor technology has been integrated into a modular extracorporeal liver support (MELS) system, combining biologic liver support with artificial detoxification technology.

Adolescent↗

PubMed2003

[Which functional diagnostic tools do German coloproctologists favour?].

AIM: We tried to evaluate the role of anorectal functional diagnostic tools according to the judgement of German coloproctologists. METHOD: Questionnaires concerning accuracy of different diagnostic tests were sent to 585 physicians specialized in coloproctology. RESULTS: 261 (44.6 %) completed forms were returned. An analysis of the answers revealed that endorectal sonography is widely (73 %) regarded as useful and reliable diagnostic tool. Though manometry is still frequently used, only 50.5 % of the coloproctologists made their decision concerning the further treatment depending on the results of this method. Other radiologic methods as defecography and colon transit time are still regularly performed, though video-defecography is not accepted by most coloproctologists. Neurological investigations as pudendal nerve terminal latency, surface-EMG and needle-EMG are exclusively applied in specialized departments. DISCUSSION: Regarding the variety of diagnostic tools and its different appraisal a consensus should be defined. The usefulness of neurological examination techniques needs to be clarified before their performance can be recommended for a wide-spread routine work up.

Colonic Diseases↗

PubMed2002

Aseptic necrosis of both femoral heads as first symptom of chronic myelogenous leukemia.

Chronic myelogenous leukemia (CML) is a disease of the elderly; in rare cases it occurs in childhood or adolescence. One complication at primary diagnosis is leukostasis, which usually causes respiratory, retinal, or central nervous symptoms. In this report we describe the case of a 24-year-old woman who developed aseptic necrosis of both femoral heads, which was successfully treated by bore holes in the femoral heads. This is a very rare complication of severe leukostasis, leading to the diagnosis of CML in this case. To our knowledge, this is the first case of an adult patient showing aseptic necrosis of femoral heads caused by leukostasis.

Adult↗

PubMed2002

[Status report on epidemiology of acute appendicitis].

The current incidence of appendicitis is about 100 per 100,000 person-years in Europe/America. Whereas the appendectomy rate is still decreasing, the incidence of appendicitis is now nearly stable. During the last 30 years the incidence of perforated appendicitis has not changed (approximately 20 per 100,000 person-years). Established risk factors for acute appendicitis are age (peak: 10-19 years), sex, and ethnic group/race. Classical theories (diet, hygiene) present illuminating models to explain the rise and fall of incidence in the last century; however, from a contemporary perspective the evidence is insufficient. The study of the epidemiology of appendicitis is complicated by the influence of referral, infrastructure, and surgical treatment strategy on the incidence of acute appendicitis. Therefore, there is a strong need for good prospective studies with high-quality data (e.g., studies directed by a central pathology department).

Acute Disease↗

PubMed2002

Extracorporeal pressure monitoring and the detection of vascular access stenosis.

Prospective monitoring of static venous pressure is an established tool to detect outflow stenoses in a vascular access. However, with this method it is not possible to identify vascular stenoses which are localized between the arterial and venous dialysis needle. We describe a new approach based on both static arterial and venous extracorporeal pressures. Pressure data of 9 dialysis patients with normal vascular access function and 9 patients with stenotic access were analyzed. Extracorporeal pressure was found to depend on the position of the heart relative to the extracorporeal blood circuit. All patients with venous outflow stenoses had an elevated ratio of arterial and venous intra-access pressure to mean arterial pressure. In case of access stenosis between arterial and venous needle the ratio of venous pressure to mean arterial pressure was normal, and only the arterial pressure ratio was elevated. We conclude that combined arterial and venous intraaccess pressure measurement normalized by mean blood pressure detects venous stenosis as well as stenosis between the arterial and venous dialysis needle. To minimize the rate of access thrombosis both arterial and venous intra-access pressure should be monitored.

Arteriovenous Shunt, Surgical↗

PubMed2001

Evaluation of a photoacoustic detector for water vapor measurements under simulated tropospheric/lower stratospheric conditions.

Although water vapor is one of the most important and certainly the most variable minor constituent of the atmosphere, accurate measurements of p(H20) with high time resolution are difficult, particularly in the cold upper troposphere/lower stratosphere. This work demonstrates that a diode laser-based photoacoustic (PA) water vapor detector is a viable alternative to current water vapor sensors for airborne measurements. The PA system was compared with a high-quality frost point hygrometer (FPH) and with a Lyman-alpha hygrometer in the pressure range of 1000-100 hPa at frost point temperatures between 202 and 216 K. These conditions were simulated in a large environmental chamberfor 14 h. Simultaneous measurements with the three instruments agreed within 6%. Nitric acid vapor interferes with the FPH measurements at low frost point temperatures but does not affect the other instruments. The sensitivity of the PA system is already sufficient for measurements in the upper troposphere, and straightforward improvements can extend its useful range above the tropopause. Rugged construction, extreme simplicity, small size, and potential for long-term automatic operation make the PA system potentially suitable for airborne measurements.

Acoustics↗

PubMed2001

Sodium phenylacetate enhances the inhibitory effect of dextran derivative on breast cancer cell growth in vitro and in nude mice.

Sodium phenylacetate (NaPa) and carboxymethyl benzylamide dextran derivative (CMDB(LS4)) are able to inhibit growth of breast tumour cells. In this study, we explored whether the combination of NaPa and CMDB(LS4)may enhance their respective inhibitory effects on the MCF-7ras cell growth in vitro and in vivo. NaPa inhibited MCF-7ras cell proliferation by reducing the DNA replication concomitantly with a recruitment of cells in G0/G1 phase and by inducing apoptosis in a dose- and time-dependent manner. The addition of CMDB(LS4)potentiated the NaPa antiproliferative effect in the manner dependent on the ratio of CMDB(LS4)and NaPa concentrations. In nude mice, CMDB(LS4)(150 mg kg(-1)) or NaPa (40 mg kg(-1)) administrated twice a week, for 7 weeks inhibited MCF-7ras xenograft growth by 40% and 60%, respectively. The treatment by both, CMDB(LS4)and NaPa, decreased tumour growth by 83% without any toxicity. To better understand the mechanism of NaPa and CMDB(LS4)action we assessed their effect on mitogenic activity of MCF-7ras conditioned medium (CM) on BALBC/3T3 fibroblasts. CMDB(LS4)added to the CM, inhibited its mitogenic activity whereas NaPa had an anti-mitogenic effect when CM was prepared from MCF-7ras cells pretreated with NaPa. Thus, the antiproliferative effects of NaPa and CMDB(LS4)involve 2 different mechanisms explaining, at least in part, the possible synergism between them. Overall, this study points to the potential use of a combination of dextran derivatives with NaPa to inhibit the breast tumour growth.

3T3 Cells↗

PubMed2001

Metabolic and electrophysiological alterations in an animal model of neocortical neuronal migration disorder.

Cortical migration disorders are a major cause for intractable epilepsy syndromes. High resolution MRI and PET are increasingly capable to identify cortical dysgenesis. In this study we used the rat freeze lesion model to investigate cortical morphological and functional changes in adult rats after induction of a cortical freeze lesion at postnatal day (p) 0. Autoradiographic measurements of basic cortical [14C]deoxyglucose metabolism showed a significant reduction up to 1 mm lateral to the lesion but no remote changes. Electrophysiological in vitro recordings revealed a significant reduction in the amplitude of stimulus-evoked field potential responses recorded lateral to the lesion as compared to medial recording sites. Our data provide further evidence that spatially restricted developmental alterations of cortical morphology cause functional changes in surrounding and histologically normal areas that need to be considered for a better understanding of the resulting pathophysiology.

Animals↗

PubMed2001

High preoperative serum carcinoembryonic antigen predicts metastatic recurrence in potentially curative colonic cancer: results of a five-year study.

INTRODUCTION: Serum carcinoembryonic antigen is used mainly for tumor follow-up to detect recurrence of colonic cancer. However, raised preoperative carcinoembryonic antigen levels may be helpful for the identification of understaged cases and of patients meriting more intensive preoperative and postoperative diagnostic workup. METHODS: From a prospectively collected database, the data on 261 patients who had curative colonic carcinoma with a minimal follow-up of five years and who had preoperative carcinoembryonic antigen levels assessed were retrieved and analyzed. Outcome parameters were local and/or distant recurrence and time to recurrence. These parameters were correlated with Dukes staging and preoperative carcinoembryonic antigen levels. RESULTS: The cumulative disease-free survival of patients with a preoperative carcinoembryonic antigen level within the normal range was significantly better than that of those whose carcinoembryonic antigen was 5 ng/ml or more (P = 0.001). No patient with carcinoembryonic antigen levels less than 1 ng/ml developed metastatic recurrence. Twenty-three percent of all patients with a raised carcinoembryonic antigen above 5 ng/ml compared with 2.1 percent of patients with carcinoembryonic antigen below 5 ng/ml developed a metastasis at two years. At five years, these figures were 37.2 percent and 7.5 percent, respectively. Dukes staging and carcinoembryonic antigen levels were found to be directly correlated (P < 0.001) when all patients were included. Carcinoembryonic antigen of more of 15 ng/ml was found to be a significant adverse prognostic indicator for disease-free survival irrespective of Dukes staging (P < 0.02). Raised carcinoembryonic antigen levels predicted distant metastatic recurrence (P < 0.001) but did not predict local recurrence (P = 0.72). CONCLUSIONS: High preoperative carcinoembryonic antigen levels above 15 ng/ml predicted an increased risk of metastatic recurrence in potentially curative colonic cancer and may indicate undetectable disseminated disease. Preoperative carcinoembryonic antigen levels predict understaging and the possibility of distant recurrence. Such patients may therefore be selected for adjuvant therapy where indicated. Therefore, carcinoembryonic antigen is complementary to conventional Dukes staging for the prediction of recurrence and survival.

Aged↗