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Biomedical subjects

M Jäger

Publications and source records attributed to M Jäger.

At least 19 recordsLinked to original sources

Intravenous iloprost: a new therapeutic option for patients with post-transplant distal limb syndrome (PTDLS).

The purpose of this study was to investigate the application of intravenous iloprost as a novel therapy for the treatment of post-transplant distal limb syndrome (PTDLS). PTDLS is a benign but disabling complication in the first year after renal transplantation. It is characterized by bilateral, often incapacitating pain in the feet and or knees on motion and a significant rise in alkaline phosphatase levels on laboratory evaluation. On MRI, bone marrow edema of the affected bone regions can be demonstrated. PTDLS differs from steroid induced osteonecrosis of the hip in terms of localization, an average cumulative steroid dosage within expected limits, and a benign outcome, as PTDLS does not progress to overt cell necrosis. From August 2003 to April 2005 we treated 10 patients with MRI-proven diagnosis of PTDLS following a standardized regimen of intravenous iloprost over 5 days. Iloprost led to prompt pain relief measured on a visual analogous scale (VAS) ranging from 1 to 10 (5.6 +/- 1.5 before vs. 2.1 +/- 1.3 after treatment, p = 0.0004). PTDLS represents a benign but disabling complication following renal transplantation. Intravenous iloprost might be a promising therapeutic concept leading to a quick relief of symptoms without relevant side effects.

Adult↗

[CERAD and NOSGER. Comparing predictive scales for dementia in a Swiss gerontopsychiatric patient population].

BACKGROUND: The Consortium to Establish a Registry for Alzheimer's Disease (CERAD) is an established screening instrument for the diagnosis of Alzheimer's disease. The Nurses Observation Scale for Geriatric Patients (NOSGER), actually developed for rating the frequency of behavioral disturbances, appears suitable for dementia screening as well. MATERIAL AND METHOD: In this retrospective study we analyze the neuropsychological data of 400 consecutive patients at our hospital with several psychiatric diagnoses and cognitive deficits. By means of logistic calculation in single and multivariable models, the predictive value of CERAD and NOSGER for dementia diagnosis was studied. RESULTS: All CERAD subtests were significant single predictors for dementia. The multivariable model with the highest prediction for probability of dementia diagnosis contained the subtests Verbal Fluency Test, Word List Recall, Constructional Practice Recall, and the Mini-Mental State Examination. However, NOSGER could not differentiate between demented and nondemented patients. CONCLUSION: In our gerontopsychiatric population, CERAD separates demented patients from nondemented ones with high predictive potency. The NOSGER does not reveal any predictive value for the diagnosis of dementia.

Aged↗

[Acute and transient psychotic disorders (ICD-10: F23). Empirical data and implications for therapy].

The defining clinical features of acute and transient psychotic disorders (ICD-10: F23) are an acute onset and a duration of psychotic symptoms not exceeding 1-3 months. Previous empirical investigations show that patients with this diagnosis have a favourable prognosis, but also a high risk of relapses (58-77%). The diagnostic stability in the further course of illness seems to be low (34-73%) with a frequent diagnostic change to schizophrenia and affective disorders being observed. As yet, data from controlled clinical trials regarding therapy do not exist. The implications for the treatment of acute and transient psychotic disorders are discussed with this background.

Evidence-Based Medicine↗

Ultrasonic standing wave manipulation technology integrated into a dielectrophoretic chip.

Several cell-based biological applications in microfluidic systems require simultaneous high-throughput and individual handling of cells or other bioparticles. Available chip-based tools for contactless manipulation are designed for either high-precision handling of individual particles, or high-throughput handling of ensembles of particles. In order to simultaneously perform both, we have combined two manipulation technologies based on ultrasonic standing waves (USWs) and dielectrophoresis (DEP) in a microfluidic chip. The principle is based on the competition between long-range ultrasonic forces, short-range dielectrophoretic forces and viscous drag forces from the fluid flow. The ultrasound is coupled into the microchannel resonator by an external transducer with a refractive element placed on top of the chip, thereby allowing transmission light microscopy to continuously monitor the biological process. The DEP manipulation is generated by an electric field between co-planar microelectrodes placed on the bottom surface of the fluid channel. We demonstrate flexible and gentle elementary manipulation functions by the use of USWs and linear or curved DEP deflector elements that can be used in high-throughput biotechnology applications of individual cells.

Electrophoresis, Microchip↗

Extensive H(+) release by bone substitutes affects biocompatibility in vitro testing.

Bone substitutes are widespread in orthopedic and trauma surgery to restore critical bony defects and/or promote local bone healing. Cell culture systems have been used for many years to screen biomaterials for their toxicity and biocompatibility. This study applies a human bone marrow cell culture system to evaluate the toxic in vitro effects of soluble components of different bone substitutes, which are already in clinical use. Different specimens of tricalcium phosphates (TCP) (Vitoss, Cerasorb), nondecalcified bovine bone (Lubboc), demineralized human bone matrices (DBM) (Grafton Flex/Putty), and collagen I/III matrix (ACI-Maix) were tested in Dulbecco's modified Eagle's medium (DMEM) and MesenCult culture solution and compared with a biomaterial-free cell culture. Biocompatibility parameters were cell viability evaluated by phase-contrast microscopy and laser flow cytometry, morphology, and the local H(+) release by bone substitutes. There were significant differences (p < 0.05) between the tested biomaterials and culture solutions. Collagen I/III, non-demineralized bovine bone, and TCP materials showed advantages for cell survival over other tested biomaterials (average values of vital cells/mL MesenCult/DMEM: Collagen I/III: 1090/1083; Vitoss: 893/483; Cerasorb: 471/523; Lubboc: 815/410; Grafton Putty: 61/44; Grafton Flex: 149/57). Especially the DBM materials lead to a significant decrease of pH, which is considered to be a major factor for cell death. DMEM culture solution supports cell survival for those bone substitutes that induce an alkaline reaction, whereas MesenCult media promotes cell vitality in biomaterials, which leads to an acidification of culture solution.

Animals↗

[Treatment of vitally endangered anorexia nervosa patients based on guardianship laws].

Anorexia nervosa is a psychiatric disorder occurring primarily in young women. Especially when chronic or the body mass index is less than 12 kg/m(2), it has a mortality of up to 20%. Often these patients are admitted to emergency units and treated internistically. If they accept psychiatric treatment, they are normally transferred to specialized psychosomatic units for further therapy. If patients are not able to accept necessary further therapy to overcome the danger to health and life, the question arises in terms of guardianship law of whether they are able to handle their personal concerns alone. After several vitally endangered anorexia nervosa patients had been admitted to our closed psychiatric ward, we developed a therapeutic concept for this subgroup of patients, taking the possibilities of guardianship law into account. This concept aims at restoring the body weight continuously and finally enable the patients to be transferred to less restrictive psychosomatic units. The chosen treatment is shown with the therapy courses of 25 patients treated according to this concept.

Adolescent↗

Avascular osteonecrosis after hyperthermia in children and adolescents with pelvic malignancies: a retrospective analysis of potential risk factors.

PURPOSE: In children with locally advanced or recurrent malignant tumours, prognosis can be improved by regional deep hyperthermia (RHT) in combination with platin-based chemotherapy. However, because of the increasing number of patients that achieve long-time remission with this therapy, it is necessary to evaluate long-term sequelae of thermochemotherapy. During the years 1993-2004 one has observed avascular osteonecrosis (AON) of the femoral head after RHT in seven children with pelvic germ cell tumours or rhabdomyosarcomas. METHODS: Although AON may develop in patients with malignancies treated with chemo- or radiotherapy alone, RHT might nevertheless contribute to the occurrence of AON. In order to determine potential risk factors for AON after RHT, this study analysed the relationship of AON to the patient's age, medical history and treatment parameters such as thermal dose equivalent and power output. RESULTS AND CONCLUSIONS: In the present study AON was associated with young age as well as intensity of hyperthermia indicated by high power levels that exceed 20 W per kg body weight and/or application of eight or more heat sessions as well as additional radiotherapy. Based on this observation, it was assumed that an optimized three dimensional thermal field modelling may be helpful to avoid hazardous temperatures in the femoral heads during RHT treatment and to reduce AON of the femoral heads.

Adolescent↗

Specific induction of pp125 focal adhesion kinase in human breast cancer.

The pp125 focal adhesion kinase (FAK) is involved in integrin-mediated cell signalling and overexpressed in a variety of solid tumours. Focal adhesion kinase expression has been correlated to invasion and metastasis, but the data on breast cancer are inconclusive. We analysed FAK mRNA, protein levels and expression patterns in primary breast cancer and normal breast tissue. FAK expression on the functional protein level and mRNA was determined in 55 matched pairs of breast cancer and corresponding normal tissue by Western blot, immunohistochemistry and RT-PCR. Using a score ranging from 0 to +5 for Western blots, we determined in normal breast tissue a score of 1.51+/-0.84 (mean+/-standard deviation), which was strongly induced to 2.91 (+/-1.22) in breast cancers (P<0.001). Overall, 45 out of 55 tissue pairs (81.8%) showed this upregulation of FAK protein in tumours in comparison to normal tissue. Immunohistochemistry confirmed these findings with a significant higher score for tumours vs physiological tissue (1.0+/-0.63 vs 2.27+/-0.91; P=0.001). Interestingly, no overall significant difference in the mRNA levels (P=0.359) was observed. In conclusion, expression levels of the FAK protein are specifically upregulated in breast cancer in comparison to matched normal breast tissue supporting its pivotal role in neoplastic signal transduction and representing a potential marker for malignant transformation.

Biomarkers, Tumor↗

Thalamic volume in first-episode and chronic schizophrenic subjects: a volumetric MRI study.

OBJECTIVE: The thalamus, as a composite of several functionally very different nuclei, is a major relay and filter station in the CNS and is significantly involved in information processing and gating. The aim of our study is to investigate first-episode and chronic patients and controls to shed light on the potential pathogenetic role of the thalamus in schizophrenia and to assess the relationship between thalamic volumes and psychopathology ratings. METHODS: Forty-three male right-handed chronic and 25 male right-handed first-episode schizophrenic patients treated at the psychiatric hospital of the Ludwig-Maximilians University in Munich and 50 male control subjects were enrolled into the study. Demographic information and current symptom profile of all schizophrenic subjects were assessed using a semistructured interview, including a variety of measures relevant to the study. Volumetry of the thalamic gray and white matter was obtained with 1.5 T MRI, using the BRAINS software application. RESULTS: No significant differences regarding thalamic volumes were detected across groups. However, negative symptoms were significantly correlated with thalamic volumes in first-episode patients, whereas duration of illness and extrapyramidal symptoms were related to thalamic volumes in chronic patients. SUMMARY: Our findings indicate that, while the thalamus might be involved in the pathogenesis of negative symptoms, thalamic volume reduction is not a required element in the pathophysiology of the schizophrenic phenotype.

Adult↗

[Bone harvesting from the iliac crest].

BACKGROUND: Autogenous bone grafts from the iliac crest are frequently harvested for autologous bone transplantation. Although an autologous bone transplant does improve the local bone healing potency, significant donor site morbidity must be considered. METHODS: In this study we elucidate special bone harvesting techniques from the iliac crest and review the literature related to clinical significance of donor site morbidity. Furthermore, our own experiences are compared and discussed critically with relevant data of other investigators. RESULTS: The increasing number of scientific publications which focus on bone harvesting techniques and related complications in recent years indicate the high interest and relevance of this issue. There is a tendency to alternatives such as biomaterials as bone substitutes, whereas the role of growth factors and cell therapeutics in the treatment of bony defects are still being evaluated in clinical studies. CONCLUSION: Although autologous, heterotopic bone transplantation is still the gold standard in the treatment of bony defects, there is a tendency towards the application of biomaterials, stem cells, and growth factors. Conscientious observation of relevant anatomic considerations during bone harvesting procedures may help to avoid complications.

Adolescent↗

Proliferation and osteogenic differentiation of mesenchymal stem cells cultured onto three different polymers in vitro.

In this study, the osteoinductive and cell-binding properties of three different resorbable polymers were evaluated by human mesenchymal stem cells (MSCs). MSCs were isolated, expanded, and cultivated onto resorbable D,D,L,L-polylactide (PLLA), collagen I/III, and polygalactin-910/polydioxanone (PGPD) scaffolds in vitro. To evaluate the influence of dexamethasone, ascorbic acid, and beta-glycerolphosphate (DAG) on osteoblast differentiation, MSCs were incubated in a DAG-enriched medium. After a 28-day period in vitro, the cellular loaded polymers were digested enzymatically by papain and HCl. The Ca(2+) content of the biomembranes was evaluated by an o-kresolphthalein-complexon reaction via photometer. A PicoGreen assay was performed for dsDNA quantification. Significant differences between the number of adherent MSCs were documented (collagen > PLLA > PGPD). Compared to the initial number of adherent cells, all biomaterials induced a significant decrease in cellular adherence after 28 days in vitro. The presence of DAG-enriched culture medium stimulated the cellular proliferation for PLLA and slightly for PGPD, whereas cell proliferation was inhibited when MSCs were cultivated onto collagen I/III. In comparison with the control groups, all biomaterials (PLLA, PGPD, and collagen I/III) showed a significant increase in local Ca(2+) accumulation under DAG stimulation after 28 days in vitro. Furthermore, collagen I/III and PLLA scaffolds showed osteoinductive properties without DAG stimulation. These results were verified by immunocytochemical stainings against osteoblast-typical markers (osteopontin and alkaline phosphatase) and completed by calcified matrix detection (von Kossa staining). MSCs were identified by CD105 and CD13 antigen expression. Corresponding to an absence of CD34, CD45, and collagen II expression, we found no chondrogenic or hematopoietic cell differentiation. The results indicate significant differences for the proliferation, differentiation, adherence, and Ca(2+) accumulation between the tested polymers in a MSC culture.

Biocompatible Materials↗

The critical size bony defect in a small animal for bone healing studies (I): Comparative anatomical study on rats' femur.

Laboratory rats are small animal models which are often used for scientific investigations in medicine. So far there are only few scientific data about the meaning of these small animal models for in vivo bone healing studies available in literature. Although the rat's femur with its cyclic loadings during gait is an appropriate model for investigations in the field of experimental orthopaedics and traumatology there is a lack of morphometric information with respect to its anatomy. The aim of this study is to evaluate the anatomy of rat femurs in two species, which are often performed in animal experimental medicine. These morphometric data should contribute to develope an appropriated osseous fragment fixation system in the rat's femur. The femurs of Wistar (WR) and Sprague Dawley (SDR) cadavers were prepared and analysed by x-rays in two standard planes. The results were compared with the corresponding data for humans by literature. It could be demonstrated that SDR showed a higher caput-collum-diaphyseal and antetorsion angle, but a lower transcondylar femur valgus angle compared to WR. Cortical thickness, bone marrow cavity diameter and femur length were higher in WR. Wistar rat's femur anatomy shows more similarities to human anatomy than Sprague Dawley rats.

Animals↗

The critical size bony defect in a small animal for bone healing studies (II): implant evolution and surgical technique on a rat's femur.

In the preclinical field of orthopaedic and trauma surgery critical size bony defects (CDS) were used to evaluate the biocompatibility and allow to investigate the osteoinductivity and -conductivity of bone substitutes. Concerning the anatomical size the laboratory rat indicates a lower limit in small animals which are appropriate for experiments on bone. The aim of this study was to define a CSD, to develop a suitable fixation system to stabilize bony fragments in CSD and to point out the specialities of the surgical technique. These informations should help for to design and practice studies concerning bone healing on rat's femur. Based on previously acquired anatomical data of rat's femur, the technical challenges and anatomical specialities of different osteosynthesis techniques in rat's femur surgery are demonstrated. Our experiences with different fixation systems and techniques lead to the development of an external fixator, which guarantees for a stable bone fragment fixation, prevents severe soft tissue damage, allows of a roentgenologic evaluation of the defect zone and prevents from undesired direct biomaterial-implant interactions. Neither the proximal nor the distal femoral nailing technique is appropriate for a stable fixation in CSD of rat's femur. To evaluate the reliability of an own developed external fixator 42 nude rats with a 4.0 mm CSD were investigated clinically and roentgenologically over 10 weeks. The external fixator showed only a small implant failure rate. A solid fusion of the bone fragments was not observed within the 10 weeks follow-up period.

Animals↗

[In vivo and in vitro bone regeneration from cord blood derived mesenchymal stem cells].

BACKGROUND: Mesenchymal stem cells with an osteoblastic differentiating potency are investigated in regard of probable tissue engineering for further clinical application. The following report describes the use of cord blood derived stem cells as an alternative to other stem cell populations for bone regenerating tissue engineering. METHODS: To demonstrate the multipotency of cord blood derived mesenchymal stem cells, unrestringated somatic stem cells (USSC) were isolated from cord blood and underwent an osteo-, chondro- and adipoblastic in vitro stimulation. To evaluate the osteoinductive potency of a porcine collagen I/III cell carrier USSC were incubated on this matrix. To investigate the in vivo effects of human USSC an athymic rat model was developed. These cells were transplanted into a femoral defect. RESULTS: Cord blood derived mesenchymal stem cells (USSC) have an in vitro multipotency and show adipo-, chondro- and osteogenic differentiation. The porcine collagen I/III carrier promoted an osteoblastic differentiation. USSC survived after xenotransplantation in an athymic rat and differentiated into osteoblasts filling the bony defect zone. CONCLUSION: Human USSC are a mesenchymal multipotent stem cell population that shows osteoblastic differentiation onto a collagen I/III carrier in vitro as well as in an athymic rat in vivo.

Adipocytes↗

[Pain management in non-juvenile, aseptic osteonecrosis].

BACKGROUND: Adult aseptic osteonecrosis (ON) represents a clinical picture with unexplained etiology. Since curative treatment of this disease often succeeds only in the early stage, pain therapy plays an important role in the treatment process. METHOD: We compared established and novel treatment options for ON as well as our own results after i.v. administration of the prostacyclin analogue iloprost with corresponding studies in the literature. RESULTS: In addition to treatment with nonsteroidal antirheumatic agents and opioids, surgical "core decompression," vasoactive medications, and hyperbaric oxygenation are effective. Treatment with iloprost for 5 days resulted in highly significant pain reduction. CONCLUSION: Symptomatic treatment is indicated in all stages of ON and curative treatment in stage I and early stage II. In cases of disease progression in the large joints, early endoprosthetic replacement is indicated to avoid secondary damage. In addition to employing vasoactive substances, a further curative treatment approach could be the use of mesenchymal stem cells.

Adult↗

[The classification of functional psychoses: the impact of ICD-10 diagnoses (research diagnostic criteria) for the prediction of the long-term course].

One major objective of Emil Kraepelin's system of the functional psychoses was to establish a prognostically relevant diagnostic classification. Following this idea, 197 first admitted inpatients from the years 1980 - 1982 were examined 15 years later in order to determine the impact of ICD-10 diagnoses (derived from first hospitalisation) for the long-term course. The long-term course was divided into the three course types single episode, episodic-remitting course and chronic course. The results showed that 57 % of the patients with schizophrenia, 50 % of the patients with persistent delusional disorders, 20 % of the patients with acute and transient psychotic disorders, 10 % of the patients with schizoaffective disorders and only 3 % of those with affective disorders developed a chronic course type. Using a logistic regression analysis, the predictive validity of the ICD-10 diagnoses was compared with those of a dimensional model based on psychopathological and demographic data. The results revealed that the predictive validity of the dimensional model (77 %) does not exceed the predictive validity of ICD-10 diagnoses (78 %).

Adult↗

[Variations of superficial nerves at the pelvis considering orthopaedic surgical approaches].

PROBLEM: Intraoperative injuries of vessels and nerves are common risks and repeatedly described in orthopaedic pelvic surgery. Especially in pelvic osteotomies or bone harvesting procedures subcutaneous nerves are at risk for damage. In this study we elucidated the variations of subcutaneous nerves by anatomic preparation exposure with regard to the anterior and posterior spines. METHODS: To investigate the different anatomic variations the iliohypogastrical, lateral cutaneous, subcostal and the cluneal nerves of 10 human cadavers were prepared and exposed bilaterally at the anterior, lateral and posterior pelvic region. For determination of anatomically important reference points the distance of these structures to the anterior superior spine was measured and compared with present datas in literature with respect to the ilioinguinal (Letournel) and iliofemoral (Smith- Petersen) approach. RESULTS: We found a high variability of superficial pelvic nerves. Our findings differ somehow with datas of recent papers. CONCLUSION: The findings of our study stress the importance of basic knowledge and thorough preparation in surgical procedures at the pelvis including harvesting bone grafts to minimize donor site morbidity.

Bone Transplantation↗

Fifteen-year follow-up of ICD-10 schizoaffective disorders compared with schizophrenia and affective disorders.

OBJECTIVE: The nosological status of schizoaffective disorders is still unclear. The aim of the present study was to compare ICD-10 schizoaffective disorders to schizophrenia and affective disorders with respect to the clinical picture and the long-term outcome. METHOD: Two hundred and forty-one first-admitted inpatients from the years 1980-1982 who fulfilled the ICD-10 criteria for schizophrenia, schizoaffective or affective disorders were included. Patients were examined at the time of first hospitalization and then followed-up after 15 years. RESULTS: With respect to the clinical picture at the time of first hospitalization ICD-10 schizoaffective disorders were distinguishable from both schizophrenia and affective disorders. However, with respect to the long-term outcome ICD-10 schizoaffective disorders had a prognosis similar to that of affective disorders. CONCLUSION: Differing prognosis implies that schizoaffective disorders should be distinguished from schizophrenia and suggests their subcategorization under affective disorders.

Adult↗