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Biomedical subjects

J Bauer

Publications and source records attributed to J Bauer.

At least 91 records · Page 5Linked to original sources
PubMed2001

[Cardiac troponin I after heart surgery corrective operation in infancy and childhood].

BACKGROUND: Perioperative myocardial damage is an important determinant for postoperative cardiac function and recovery. Cardiac troponin I (cTNI) is a specific marker for myocardial damage. The aim of our study was to evaluate pre- and postoperative cTNI levels, the pattern of elevation in the first four postoperative days and the prognostic value after pediatric cardiac operation. METHODS: Cardiac troponin I levels were measured in 115 children mean age 36 +/- 45 months (range 4 days to 189 months) undergoing elective operation of a congenital heart defect. Routine measurements were made preoperatively, immediately after cardiopulmonary bypass and serially 8, 18, 42, 90, 138 hours thereafter. Data from 13 patients undergoing surgery without cardiopulmonary bypass served as controls. Postoperative cTNI levels were correlated with intra- and postoperative parameters (such as duration of aortic crossclamping, cardiopulmonary bypass time and need for postoperative inotropic support). RESULTS: All preoperative cTNI levels were in the normal range. Postoperatively, the highest median cTNI levels were found in patients after repair of tetralogy of Fallot (TOF), atrioventricular septal defect (AVSD) and implantation of a homo- or xenograft. Postoperative cTNI levels correlated significantly with duration of cardiopulmonary bypass and aortic crossclamping, operative approach (ventriculotomy versus atriotomy) and inotropic support (p < 0.0001). Peak cTNI levels were found immediately after surgery in 77.4% of our patients, 8 hours postoperative in 13.9% and at 18 hours after the surgery in 5.2% of the patients. In three children cTNI continued to increase; a secondary increase was found in one patient. Two of these children died, two had a prolonged postoperative recovery. CONCLUSION: The postoperative level of cardiac troponin I could be used as a marker of perioperative myocardial injury caused by ischemia and operative trauma. Peak levels usually could be obtained immediately after surgery, but a further increase of cTNI during the following 18 hours may occur and is not necessarily related to impaired recovery. However still increasing cTNI levels after 18 hours postoperatively and a secondary increase as well may be used as indicators of poor outcome.

Adolescent↗
PubMed2001

Transgenic mice with cardiac-specific expression of activating transcription factor 3, a stress-inducible gene, have conduction abnormalities and contractile dysfunction.

Activating transcription factor 3 (ATF3) is a member of the CREB/ATF family of transcription factors. Previously, we demonstrated that the expression of the ATF3 gene is induced by many stress signals. In this report, we demonstrate that expression of ATF3 is induced by cardiac ischemia coupled with reperfusion (ischemia-reperfusion) in both cultured cells and an animal model. Transgenic mice expressing ATF3 under the control of the alpha-myosin heavy chain promoter have atrial enlargement, and atrial and ventricular hypertrophy. Microscopic examination showed myocyte degeneration and fibrosis. Functionally, the transgenic heart has reduced contractility and aberrant conduction. Interestingly, expression of sorcin, a gene whose product inhibits the release of calcium from sarcoplasmic reticulum, is increased in these transgenic hearts. Taken together, our results indicate that expression of ATF3, a stress-inducible gene, in the heart leads to altered gene expression and impaired cardiac function.

Activating Transcription Factor 3↗
PubMed2001

Hippocampal apoptosis in major depression is a minor event and absent from subareas at risk for glucocorticoid overexposure.

Glucocorticoid (GC) overexposure in animals has been implicated in hippocampal dysfunctioning and neuronal loss. In major depression, hypercortisolemia, hypothalamic-pituitary-adrenocortical-axis alterations, and reduced hippocampal volumes are commonly observed; hence, hippocampal neurodegeneration is also expected. To study possible GC-related pathology, we investigated hippocampal tissue of 15 major-depressed patients, 16 matched controls, and 9 steroid-treated patients, using in situ-end-labeling for DNA fragmentation and apoptosis, and heat-shock protein 70 and nuclear transcription factor kappaB immunocytochemistry for damage-related responses. No obvious massive cell loss was observed in any group. In 11 of 15 depressed patients, rare, but convincing apoptosis was found in entorhinal cortex, subiculum, dentate gyrus, CA1, and CA4. Also in three steroid-treated patients, apoptosis was found. Except for several steroid-treated patients, heat-shock protein 70 staining was generally absent, nor was nuclear transcription factor-kappaB activation found. The detection in 11 of 15 depressed patients, in three steroid-treated, and in one control patient, demonstrates for the first time that apoptosis is involved in steroid-related changes in the human hippocampus. However, in absence of major pyramidal loss, its rare occurrence, that notably was absent from areas at risk for GC damage such as CA3, indicates that apoptosis probably only contributes to a minor extent to the volume changes in depression.

Adolescent↗
PubMed2001

Validation of an AAS method for the determination of platinum in biological fluids from patients receiving the oral platinum derivative JM216.

A flameless atomic absorption spectrometric (AAS) method has been developed and validated for the determination of platinum (Pt) in human plasma, plasma ultrafitrate and urines from cancer patients receiving the orally available platinum derivative, JM216. Sample pretreatment is minimal for urine, which is diluted with 10% HCl prior to AAS analysis. Pt analysis in plasma requires the application of the matrix modifier 5% Triton X-100 directly onto the integrated L'vov platform of the graphite furnace prior to the addition of plasma samples. For Pt in ultrafiltrates, enhanced sensitivity is achieved by pre-concentrating ultrafiltrate samples onto the platform prior to the ashing/atomisation step. The AAS program was set specifically for each considered matrix enabling to achieve limit of quantitations as low as 50, 10 and 5 ng Pt ml(-1) for urine, plasma and plasma ultrafiltrate, respectively. The calibration was linear (r(2)>0.993) over the working range 5-150 ng Pt ml(-1). The method has been validated according to the Recommendations on Bioanalytical Methods Validation. The stability of Pt in samples has been explored, as well as the specificity of the method. In the urine intra-assay precision of control samples at 60, 90 and 140 ng Pt ml(-1) is always lower than 3.0, 1.3 and 4.7%, respectively, with concentrations not deviating more than -5.5 to -1.0% from their nominal values, while inter-assay precision is within 5.7-7.7% and inter-assay deviation within the -1.9 to +4.3% range. Intra-assay precision of plasma control samples at 20, 70 and 140 ng Pt ml(-1) is always lower than 8% and concentrations never deviating more than 7.1% from their nominal values. Inter-assay precision of plasma control samples is always lower than 9% with inter-assay deviation from their nominal concentrations within the -3.9 to +1.8% range. In plasma ultrafiltrate, intra-assay CVs of control samples at 12, 25 and 45 ng Pt ml(-1) are always lower than 2.6, 1.7 and 6.8%, respectively, with concentrations not deviating more than -2.6 to -0.2% from their nominal values, while inter-assay CVs are within 5.1-9.5% and inter-assay deviation within the -1.6 to +5.3% range. The proposed method has, therefore, the required performance to measure Pt in biological samples and has been successfully applied to the determination of Pt in samples from cancer patients receiving JM216 in a phase I (daily administration for 14 days, dose escalation 10-50 mg m(-2)) and a phase II (fixed dose 120 mg m(-2) over 5 days) clinical study. In phase I study, both total and ultrafiltrable Pt accumulated upon repetitive dosings, showed long elimination half-lives (t(1/2)) and were measurable 2 weeks after the end of JM216 administration.

Administration, Oral↗
PubMed2001

Neuroactive steroids and seizure susceptibility.

There is increasing clinical and experimental evidence that hormones, in particular sex steroid hormones, influence neuronal excitability and other brain functions. The term 'neuroactive steroids' has been coined for steroids that interact with neurotransmitter receptors. One of the best characterized actions of neuroactive steroids is the allosteric modulation of GABA(A)-receptor function via binding to a putative steroid-binding site. Since neuroactive steroids may interact with a variety of other membrane receptors, excitatory as well as inhibitory, they may have an impact on the excitability of specific brain regions. Neuronal excitability is enhanced by estrogen, whereas progesterone and its metabolites exert anticonvulsant effects. Testosterone and corticosteroids have less consistent effects on seizure susceptibility. Apart from these particular properties, neuroactive steroids may regulate gene expression via progesterone receptors. Based on their molecular properties, these compounds appear to have a promising therapeutical profile for the treatment of different neuropsychiatric diseases including epilepsy. This review focuses on the effects of neuroactive steroids on neuronal excitability and their putative impact on the physiology of epileptic disorders.

Adrenal Cortex Hormones↗
PubMed2001

Ritonavir: an extraordinary example of conformational polymorphism.

PURPOSE: In the summer of 1998, Norvir semi-solid capsules supplies were threatened as a result of a new much less soluble crystal form of ritonavir. This report provides characterization of the two polymorphs and the structures and hydrogen bonding network for each form. METHODS: Ritonavir polymorphism was investigated using solid state spectroscopy and microscopy techniques including solid state NMR, Near Infrared Spectroscopy, powder X-ray Diffraction and Single crystal X-ray. A sensitive seed detection test was developed. RESULTS: Ritonavir polymorphs were thoroughly characterized and the structures determined. An unusual conformation was found for form II that results in a strong hydrogen bonding network A possible mechanism for heterogeneous nucleation of form II was investigated. CONCLUSIONS: Ritonavir was found to exhibit conformational polymorphism with two unique crystal lattices having significantly different solubility properties. Although the polymorph (form II) corresponding to the "cis" conformation is a more stable packing arrangement, nucleation, even in the presence of form II seeds, is energetically unfavored except in highly supersaturated solutions. The coincidence of a highly supersaturated solution and a probable heterogeneous nucleation by a degradation product resulted in the sudden appearance of the more stable form II polymorph.

Calorimetry, Differential Scanning↗
PubMed2001

High incidence of central nervous system involvement in patients with metastatic or locally advanced breast cancer treated with epirubicin and docetaxel.

BACKGROUND: Clinically overt central nervous system (CNS) involvement occurs in 10%-15% of patients with advanced breast cancer. PATIENTS AND METHODS: The International Breast Cancer Study Group (IBCSG) conducted a dose-finding phase I trial of epirubicin (E) and docetaxel (D) as first-line therapy in advanced breast cancer patients. The study was expanded into a phase II at the recommended doses of E 90 mg/m2 and D 75 mg/m2 every three weeks. From July 1996 to May 1998, a total of 92 patients (median age 50 years) entered the two studies. RESULTS: Twenty-eight out of ninety-two patients treated with the combination of E and D (30%) developed CNS metastases (95% confidence limits, 26%-35%), which were cerebral in twenty-five patients, leptomeningeal in two, and both in one. Of these 28 patients, 19 (68%) had an objective response. Median time for the development of CNS metastases from the start of chemotherapy was 15 months (range 5-42), if excluding the 6 patients presenting CNS progression within 3 months from start of treatment. It is notable that 11 patients (39%) had progression in the CNS only. Median survival from appearance of brain metastases in the whole group was only three months (range 1-22). C-erbB-2 overexpression was found in 14 out of 16 patients (87%) in whom the assay was performed (3+ in 10, 2+ in 1 and 1+ in 3 cases). CONCLUSIONS: As anthracycline- and taxane-containing regimens are increasingly used both in the metastatic and in the adjuvant setting, a careful monitoring of any neurological symptom is advisable. Our preliminary observation on the possible increase of incidence of CNS involvement in patients with advanced breast cancer receiving this effective drug combination requires further evaluation.

Adult↗
PubMed2001

Heart transplantation in children and infants: short-term outcome and long-term follow-up.

Since 1988, 82 heart transplants have been performed in 80 infants and children. Diagnoses pretransplant were: hypoplastic left heart syndrome (HLHS) (n = 43); cardiomyopathy (n = 19); endocardial fibroelastosis (n = 6); and other complex congenital heart diseases (n = 12). Age at transplantation was < 1 yr in 61 patients. Overall survival rate was 79% at 1 yr and 73% at 5 and 10 yr. To date, 20 patients have died after transplantation. Causes of death were: rejection (eight patients); right ventricular failure (four patients); transplant coronary artery disease (TCAD) (two patients); and other causes (six patients). In the majority of patients somatic growth is not impaired, and renal function is reduced (but stable) in all patients. Two patients developed post-transplant lymphoproliferative disease, which was treated successfully. Major long-term morbidity is neurologic deficit - severe in three patients and minor in six. TCAD was present or suspected in six surviving patients. We conclude that heart transplantation in infants and children can be performed with good early and late results. Quality of life is excellent in most patients. TCAD, however, will become an increasing problem in the long term.

Child↗
PubMed2001

Non-human primate models of multiple sclerosis.

The phylogenetic proximity between non-human primate species and humans is reflected by a high degree of immunological similarity. Non-human primates therefore provide important experimental models for disorders in the human population that are caused by the immune system, such as autoimmune diseases. In this paper we describe non-human primate models of multiple sclerosis, a chronic inflammatory and demyelinating disease of the human central nervous system. While reviewing data from the literature and our own research we will discuss the unique role of such models in the research of basic disease mechanisms and the development of new therapies.

Animals↗
PubMed2001

Dermcidin: a novel human antibiotic peptide secreted by sweat glands.

Antimicrobial peptides are an important component of the innate response in many species. Here we describe the isolation of the gene Dermcidin, which encodes an antimicrobial peptide that has a broad spectrum of activity and no homology to other known antimicrobial peptides. This protein was specifically and constitutively expressed in the sweat glands, secreted into the sweat and transported to the epidermal surface. In sweat, a proteolytically processed 47-amino acid peptide was generated that showed antimicrobial activity in response to a variety of pathogenic microorganisms. The activity of the peptide was maintained over a broad pH range and in high salt concentrations that resembled the conditions in human sweat. This indicated that sweat plays a role in the regulation of human skin flora through the presence of an antimicrobial peptide. This peptide may help limit infection by potential pathogens in the first few hours following bacterial colonization.

Amino Acid Sequence↗
PubMed2001

Metabolites of Monascus ruber in silages.

A total of 233 silages were examined and found that Monascus ruber was present in 43 samples with counts between 1 x 10(3) and 9 x 10(6) colony-forming units (CFU)/g (mean: 2 x 10(5) CFU/g). Monacolin K(L) and the hydroxy acid monacolin K(A) were detected by liquid chromatography-mass spectrometry in 45 and 50 of 233 samples at levels ranging from 25-15 600 and 28-65 400 microg/kg, respectively. Citrinin was found with high-performance liquid chromatography-fluorescence detection (FLD) in 14 (6%) samples, the concentrations varied between 2.4 and 64.2 microg/kg. The concentrations of citrinin were low and toxic effects are not anticipated. Monacolin K(A) and monacolin K(L) occur frequently and in considerable amounts in silages. These metabolites are believed to influence the metabolic activity of rumen anaerobic fungi resulting in a poorer digestion of crude fibre.

Animals↗
PubMed2001

A strikingly constant ratio exists between Langerhans cells and other epidermal cells in human skin. A stereologic study using the optical disector method and the confocal laser scanning microscope.

Langerhans cells play an important part in the immune surveillance of the human epidermis. Therefore, a certain distribution and numerical relationship to other epidermal cells can be expected. To quantify epidermal Langerhans cells population extensive studies have been performed using two-dimensional quantification methods on vertical sections or epidermal sheet preparations. Whereas methods using vertical sections were complicated considerably by the sampling procedure, the dendritic shape, and the suprabasal, nonrandom distribution of Langerhans cells, epidermal sheet preparations have their limitations regarding the numerical relationship of Langerhans cells to total epidermal cells and the epidermal morphology as such. In order to improve the validity of data the three-dimensional dissector method combined with confocal laser scanning microscopy has been applied to quantify the number of Langerhans cells and other epidermal cell nuclei per volume unit in cryosections of 24 punch biopsies of normal breast skin of eight women. Furthermore, the ratio of Langerhans cells to other epidermal cells, their number per biopsy, and per skin surface area were calculated. To minimize the bias by shrinkage the reference volume was estimated using Cavalieri's principle. A constant ratio of one Langerhans cells to 53 other epidermal cells was identified in breast skin (interindividual correlation coefficient: 0.952, p < 0.0001). Thus, Langerhans cells represent 1.86% of all epidermal cells; however, a wide interindividual range was found for the number of Langerhans cells per mm2 (912-1806; mean +/- SD 1394 +/- 321) and other epidermal cells per mm2 (47,315-104,588; mean +/- SD 73,952 +/- 19,426). This explains the conflicting results achieved by conventional morphometric assessments relating cell numbers to skin surface area, ignoring the varying thickness of the epidermis. The surprisingly constant relationship of Langerhans cells to other epidermal cells stresses the hypothesis of an epidermal Langerhans cells unit where one Langerhans cells seems to be responsible for the immune surveillance of 53 epidermal cells.

Adult↗
PubMed2001

Interactions between hormones and epilepsy in female patients.

Epilepsy and epileptic seizures may influence the release of hormones from the hypothalamus and the pituitary. After complex-partial seizures or generalized tonic-clonic seizures, serum prolactin increases in about two thirds of cases. Apart from this transient effect, interictal epileptic discharges from the temporal lobe may exert a prolonged influence on hormone release. Changes in luteinizing hormone (LH) pulse frequency and increased prolactin levels have been reported. As a consequence, menstrual cycles may be disturbed. The cyclic change of sex serum hormones during the ovulatory menstrual cycle may have an impact on seizure occurrence during the days of ovulation and/or menstruation (e.g., catamenial seizures). By a supplementation of progesterone during the second half of anovulatory cycles, a decrease of seizure frequency can be achieved.

Epilepsy↗
PubMed2001

On the association between valproate and polycystic ovary syndrome.

Recent studies by Isojärvi et al. have raised the issue of an increased incidence of polycystic ovary syndrome (PCOS) in women with epilepsy treated with valproate (VPA) and have proposed replacement with lamotrigine (LTG). Polycystic ovaries (PCO) are a common finding, with a prevalence >20% in the general population, and are easily detected by pelvic or vaginal ultrasonography, whereas PCOS is comparatively rare: few women with PCO have fully developed PCOS, which includes hirsutism, acne, obesity, hypofertility. hyperandrogenemia, and menstrual disorders. From an extensive review of the current literature, it appears that there are no reliable data on the actual prevalence of PCOS in normal women and in women with epilepsy. The pathogenesis of PCO is multifactorial, including genetic predisposition and the intervention of environmental factors, among which weight gain and hyperinsulinism with insulin resistance may play a part. The roles of central (hypothalamic/pituitary), peripheral, and local ovarian factors are still debated. PCO and PCOS appear to be more frequent in women with epilepsy, but there are no reliable data showing a greater prevalence after VPA. The recent studies by Isojärvi et al. may have been biased by the retrospective selection of patients. To date, there is no reason to contraindicate the use of VPA in women with epilepsy. However, patients should be informed about the risk of weight gain and its consequences.

Adolescent↗
PubMed2001

Psychogenic seizures mimicking juvenile myoclonic epilepsy: case reports.

We describe two patients with psychogenic seizures of rare semiology. Both patients (a 23-year-old man and a 26-year-old woman) attended the emergency department because status epilepticus with myoclonic seizures had been diagnosed. Seizures were documented with video-electroencephalography. Semiology of seizures were brief myoclonia of both arms resulting in a short elevation of both arms without impairment of consciousness. Ictal EEG registration was without abnormal finding. Psychiatric diagnostic assessment suggested a dissociative disorder and mild depression, respectively. During psychiatric treatment seizures occurred only rarely within a 3-5 months follow-up. One should be aware that juvenile myoclonic epilepsy may be mimicked by psychogenic seizures

Adult↗
PubMed2001

Course of chronic focal epilepsy resistant to anticonvulsant treatment.

Sixty-three patients (32 women, 31 men), chronically treated with carbamazepine, phenytoin, valproate and/or phenobarbital, were investigated. Mean age at manifestation of epilepsy was 16.4 years; mean age at onset of documentation of seizure frequency was 33.7 years; mean duration of follow-up was 104.8 months; mean number of documented seizures per patient was 313.2. A statistical analysis of seizure diaries was performed. For each day the entries were the number of seizures per day. Linear trends, the amount of variance of the seizure frequency compared to randomly distributed events, were computed with the resulting coefficients fitting a general linear regression model. Non-random aggregations (clusters) were searched for as well as gaps of seizure manifestation. A similar number of patients exhibited a decrease (30%) or increase (29%) of seizure frequency during the course of epilepsy. The variance of the daily seizure frequency was in most patients (78%) significantly higher or lower (5%) than corresponding random distributions. The coupling coefficient to the day before was significantly larger than zero (indicating seizure clustering) in 57% of patients. Significant rhythmic components in seizure profiles (quasi-weekly or quasi-monthly) were found in 31 patients (both male and female). Periods of increased seizure frequency (clusters) manifested in 62% of patients; seizure gaps of at least 1 year occurred in 29 patients followed by seizure relapses in 20 patients. In conclusion, there is no evidence for a unique type of course in chronic focal epilepsy in patients on antiepileptic drugs.

Adult↗
PubMed2001

Remote percutaneous renal access using a new automated telesurgical robotic system.

Previous clinical application of remote telesurgery has been the use of a novel system of video teleconferencing equipment along with remote control of a laparoscopic camera at distances over 11,000 miles. Recently, a robotic system has been developed to assist with percutaneous renal surgery. This robot has been incorporated into the telesurgical system to allow remote needle placement into the renal collecting system under radiological guidance. The main component of the telesurgical system is a low degree of freedom robot called "PAKY" (percutaneous access of the kidney). It is custom designed for fluoroscopic guided percutaneous needle insertion into the renal collecting system. The robot is a six-degrees of freedom device. However, when the skin entry site is fixed and held in position, only two degrees of freedom are required to orient the needle in the correct plane for accurate insertion. Remote control of the robot was accomplished over a plain old telephone system (POTS) line. On June 17, 1998, the first remote telerobotic percutaneous renal access procedure was performed between the Johns Hopkins Hospital, Baltimore, Maryland, and Tor Vergata University, Rome, Italy. This new telesurgical robot was successful in term of obtaining percutaneous access within 20 min, with two attempts to obtain entry into the collecting system. This robot represents the first system for performing remote telesurgical interventions in the kidney and demonstrates the feasibility and safety of assisting accurate and rapid needle access to the kidney during percutaneous procedures.

Aged↗