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J Bauer

Publications and source records attributed to J Bauer.

At least 37 records · Page 2Linked to original sources
PubMed1998

[Significance of hepatic cytochrome P450 enzymes for psychopharmacology].

Nearly all psychotropic drugs are metabolized by hepatic cytochrome P450-enzymes. In humans, there are 5 isoenzymes involved in this process. The activity of these enzymes can be modulated by a number of commonly used drugs, yielding potentially hazardous interactions. Most of the recently introduced selective serotonin reuptake inhibitors are potent inhibitors of cytochrome P450 enzymes. Thus, the plasma concentrations of tricyclic antidepressants or clozapine might be elevated into toxic levels. In contrast, carbamazepine induces most of the isoenzymes. This potentiates the elimination of tricyclics and antipsychotics and might cause a serious risk for the recurrence of depressive or psychotic symptoms. Moreover, 5-10% of the population are slow metabolizers of CYP2D6. This group is prone to increased adverse effects of moderately dosed medication. This review systematically points out the reported or predicted pharmacokinetic drug interactions in psychopharmacology focussing on clinical significance.

Cytochrome P-450 Enzyme Inhibitors↗
PubMed1998

Physiological and genetic characterisation of osmosensitive mutants of Saccharomyes cerevisiae.

The screening of 20,000 Saccharomyces cerevisiae random mutants to identify genes involved in the osmotic stress response yielded 14 mutants whose growth was poor in the presence of elevated concentrations of NaCl and glucose. Most of the mutant strains were more sensitive to NaCl than to glucose at the equivalent water activity (aw) and were classified as salt-sensitive rather than osmosensitive. These mutants fell into 11 genetic complementation groups and were designated osr1-osr11 (osmotic stress response). All mutations were recessive and showed a clear 2(+) : 2(-) segregation of the salt-stress phenotype upon tetrad analysis when crossed to a wild-type strain. The complementation groups osr1, osr5 and osr11 were allelic to the genes PBS2, GPD1 and KAR3, respectively. Whereas intracellular and extracellular levels of glycerol increased in the wild-type strains when exposed to NaCl, all mutants demonstrated some increase in extracellular glycerol production upon salt stress, but a number of the mutants showed little or no increase in intracellular glycerol concentrations. The mutants had levels of glycerol-3-phosphate dehydrogenase, an enzyme induced by osmotic stress, either lower than or similar to those of the parent wild-type strain in the absence of osmotic stress. In the presence of NaCl, the increase in glycerol-3-phosphate dehydrogenase activity in the mutants did not match that of the parent wild-type strain. None of the mutants had defective ATPases or were sensitive to heat stress. It is evident from this study and from others that a wide spectrum of genes is involved in the osmotic stress response in S. cerevisiae.

Cell Division↗
PubMed1998

Pharmacokinetics of temozolomide in association with fotemustine in malignant melanoma and malignant glioma patients: comparison of oral, intravenous, and hepatic intra-arterial administration.

PURPOSE: Depletion of the DNA repair enzyme O6-alkylguanine-DNA alkyltransferase (AT) has been shown to increase tumor sensitivity to chloroethylnitrosoureas. Temozolomide (TMZ), an analogue of dacarbazine, can deplete AT, suggesting that it may be used to sensitize tumors to chloroethylnitrosoureas. However, the influence of nitrosoureas on the pharmacokinetics of TMZ is unknown, and a pilot study was performed to assess the pharmacokinetics of TMZ given via, various routes to 29 patients (27 malignant melanomas, 2 gliomas) with or without sequential administration of i.v. fotemustine. METHODS: On day 1, TMZ was given intravenously (i.v.), orally (p.o.), or by intra-hepatic arterial infusion (h.i.a.) at four ascending dose levels (150 to 350 mg/m2 per day). On day 2 the same dose of TMZ was given by the same route (or by another route in six patients for determination of its bioavailability), followed 4 h later by fotemustine infusion at 100 mg/m2. Plasma and urinary levels of TMZ were determined on days 1 and 2 by high-performance liquid chromatography after solid-phase extraction. RESULTS: The pharmacokinetics of i.v. TMZ appeared linear, with the area under the curve (AUC) increasing in proportion to the dose expressed in milligrams per square meter (r = 0.86 and 0.91 for days 1 and 2, respectively). The clearance after i.v. administration was 220 +/- 48 and 241 +/- 39 ml/min on days 1 and 2, respectively. The apparent clearance after p.o. and h.i.a. administration was 290 +/- 86 and 344 +/- 77 ml/min, respectively. The volume of distribution of TMZ after i.v., p.o., and h.i.a. administration was 0.4, 0.6, and 0.6 l/kg on day 1 and 0.5, 0.5, and 0.6 l/kg on day 2, respectively. The absolute bioavailability of TMZ was 0.96 +/- 0.1, regardless of the sequence of the i.v.-p.o. or p.o.-i.v. administration, confirming that TMZ is not subject to a marked first-pass effect. A comparison of TMZ pharmacokinetics after i.v. and h.i.a. treatment at the same infusion rate revealed little evidence of hepatic extraction of TMZ. However, the systemic exposure to TMZ (AUC) appeared to decrease at a lower infusion rate. TMZ excreted unchanged in the urine accounted for 5.9 +/- 3.4% of the dose, with low within-patient and high interpatient variability. TMZ crosses the blood-brain barrier and the concentration detected in CSF amounted to 9%, 28%, and 29% of the corresponding plasma levels (three patients). The equilibrium between plasma and ascitic fluid was reached after 2 h (assessed in one patient). CONCLUSION: The sequential administration of fotemustine at 4 h after TMZ treatment had no clinically relevant influence on the pharmacokinetics of TMZ. The potential clinical effect of TMZ given by h.i.a. or by locoregional administration has yet to be established, as has the impact of the infusion duration on patients' tolerance and response rate.

Administration, Oral↗
PubMed1998

[Heart transplantation in infancy: experiences at the Giessen Pediatric Heart Center].

From June 1988 to December 1996 heart transplantations were performed in 36 newborns and infants below one year of age. Diagnosis were hypoplastic left heart syndrome (n = 26), endocardial fibroelastosis (n = 4), cardiomyopathy (n = 3), and other complex congenital heart defects (n = 3). Mean waiting time for transplantation was 52 days, the mean donor-recipient bodyweight ratio was 1.8. Seven patients (19%) died after transplantation mainly within the first month after transplantation. The cumulative probability of survival is 79% in all patients. The influence of increasing experience is indicated when patients transplanted from 1988-1993 (n = 15) are compared with transplants from 1994-1996 (n = 21). The overall survival in the first group was 50%, whereas patients transplanted from 1994 showed a probability of survival of 92%. The 1-year survival rate in the later group was 100%. In 20 patients a total of 31 rejection episodes were observed. 2 infants died due to rejection. 71% of all rejections occurred during the first month after transplantation. Renal function was slightly impaired one year after transplantation in all patients without tendency for deterioration in the sequel. The somatic development is normal in nearly all infants and the quality of life is excellent. All infants live at home without any restrictions. Two patients, however, suffer from a neurologic deficit. Until now there is no evidence of coronary vascular disease or malignancy. Heart transplantation is in our opinion a reconsiderable alternative in the treatment of complex cardiac disease and cardiomyopathy in infants.

Cause of Death↗
PubMed1998

Early-onset Alzheimer's disease due to mutations of the presenilin-1 gene on chromosome 14: a 7-year follow-up of a patient with a mutation at codon 139.

Mutations in the presenilin-1 gene (PS-1 gene) on chromosome 14 have recently been identified as a cause of familial early-onset Alzheimer's disease (EOAD). To our knowledge, only two German EOAD patients with mutations in the PS-1 gene have been identified thus far. Herein we report the case of a German EOAD patient with a family history of dementia and a missense mutation at codon 139 (M139V) of the PS-1 gene. The patient came to our clinic for the first time when he was 44 years old. During the following 7 years, his Mini-Mental State Examination (MMSE) score dropped from 24 to 0. Myocloni were an early neurological symptom that was already present during the first consultation. We could demonstrate that myoclonic activity was of cortical origin using a back-averaging method. Magnetic resonance imaging (MRI) revealed only slight changes in the early stage of the disease. Follow-up MRI studies showed progression of bitemporal ventricular enlargement and progressive frontal and temporal cortical atrophy. Although the majority of EOAD patients belong to the sporadic (non-genetic) type of AD, early-onset dementia, early myocloni and a familial history of AD should direct attention to the possibility of a genetic form of AD.

Adult↗
PubMed1998

The Family System Test (FAST). A pilot study in families with a young adult member with cancer.

The impact of a cancer diagnosis upon a family has become a focus of clinical interest, but few scientific studies have been completed in this area. The objectives of this pilot study were twofold: first, to test the applicability of the Family System Test (FAST) in families (n = 5) with a young adult member with cancer and secondly to evaluate patterns of interactions within these families. Results show that the FAST is applicable and useful to evaluate the different perceptions of hierarchy and cohesion--two essential variables--within these families. The great majority of family members represented their relationships as balanced (i.e., cohesive and moderately hierarchical). However, contrary to nonclinical families, fathers had a less positive view than mothers and patients: fathers more often perceived family and parenteral relations as unbalanced, and also more often perceived a reversal of hierarchy and a cross-generational coalition within the family. Implications for future research and clinical care are discussed.

Adaptation, Psychological↗
PubMed1998

Histopathological characterization of magnetic resonance imaging-detectable brain white matter lesions in a primate model of multiple sclerosis: a correlative study in the experimental autoimmune encephalomyelitis model in common marmosets (Callithrix jacchus).

Experimental autoimmune encephalomyelitis in the common marmoset, a nonhuman primate species (Callithrix jacchus), is a new model for multiple sclerosis. Given the close immunological relationship between marmosets and humans, it is an attractive model for investigating immunopathological pathways relevant to multiple sclerosis and to evaluate new treatments for the disease. Unlike in the originally documented model, experimental autoimmune encephalomyelitis induced without the use of Bordetella pertussis led to a chronic disease of moderate severity. The clinical course of experimental autoimmune encephalomyelitis in the present model was mainly chronic and progressive, but periods of incomplete remission did occur. At the chronic stage of the disease, actively demyelinating lesions were found together with inactive demyelinated and remyelinated (shadow) plaques. Before immunization and during clinically active experimental autoimmune encephalomyelitis, T1- and T2-weighted magnetic resonance brain images were obtained. Correlation of the data from the magnetic resonance images and the neuropathology analysis revealed that the hyperintense regions in T2-weighted images represented both active and inactive remyelinating lesions. Quantification showed that the number of lesions in T2-weighted magnetic resonance images equalled those found by pathological examination, and thus T2-weighted magnetic resonance imaging can be used to discern the total lesion load. Extravasation of gadolinium-diethylenetriamine-penta-acetic acid (triple dose) was found only in lesions, which by histopathology were shown to be engaged in the process of active demyelination.

Animals↗
PubMed1998

T-cell apoptosis in inflammatory brain lesions: destruction of T cells does not depend on antigen recognition.

Elimination of inflammatory T cells by apoptosis appears to play an important role in the down-regulation of inflammation in the central nervous system. Here we report that apoptosis of T lymphocytes occurs to a similar extent in different models of autoimmune encephalomyelitis. Apoptosis is restricted to cells located in the neuroectodermal parenchyma, thereby leaving T cells present in the brain's connective tissue compartments unharmed. Death of T cells in the parenchyma does not depend on antigen presentation by resident microglial cells or astrocytes. Adoptive transfer experiments with T lymphocytes carrying a specific genetic marker revealed that in the central nervous system these cells are destroyed regardless of their antigen specificity or state of activation. Although many of both antigen-dependent and -independent mechanisms in the induction of T-cell apoptosis may act simultaneously, our results suggest that the nervous system harbors a specific, currently undefined, mechanism that effectively eliminates infiltrating T lymphocytes.

Animals↗
PubMed1998

Oligodendrocyte apoptosis and primary demyelination induced by local TNF/p55TNF receptor signaling in the central nervous system of transgenic mice: models for multiple sclerosis with primary oligodendrogliopathy.

The scientific dogma that multiple sclerosis (MS) is a disease caused by a single pathogenic mechanism has been challenged recently by the heterogeneity observed in MS lesions and the realization that not all patterns of demyelination can be modeled by autoimmune-triggered mechanisms. To evaluate the contribution of local tumor necrosis factor (TNF) ligand/receptor signaling pathways to MS immunopathogenesis we have analyzed disease pathology in central nervous system-expressing TNF transgenic mice, with or without p55 or p75TNF receptors, using combined in situ terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling and cell identification techniques. We demonstrate that local production of TNF by central nervous system glia potently and selectively induces oligodendrocyte apoptosis and myelin vacuolation in the context of an intact blood-brain barrier and absence of immune cell infiltration into the central nervous system parenchyma. Interestingly, primary demyelination then develops in a classical manner in the presence of large numbers of recruited phagocytic macrophages, possibly the result of concomitant pro-inflammatory effects of TNF in the central nervous system, and lesions progress into acute or chronic MS-type plaques with axonal damage, focal blood-brain barrier disruption, and considerable oligodendrocyte loss. Both the cytotoxic and inflammatory effects of TNF were abrogated in mice genetically deficient for the p55TNF receptor demonstrating a dominant role for p55TNF receptor-signaling pathways in TNF-mediated pathology. These results demonstrate that aberrant local TNF/p55TNF receptor signaling in the central nervous system can have a potentially major role in the aetiopathogenesis of MS demyelination, particularly in MS subtypes in which oligodendrocyte death is a primary pathological feature, and provide new models for studying the basic mechanisms underlying oligodendrocyte and myelin loss.

Animals↗
PubMed1998

Cardiorespiratory stability of premature boys and girls during kangaroo care.

The objective of the investigation was to study the stability of the cardiorespiratory system of 20 premature boys and girls during maternal kangaroo care (KC) and in the incubator. Stability of heart rate, respiration and oxygen saturation was compared in a pretest-test-posttest design by means of a stability score. The three stability items and the total stability did not change significantly during the three conditions. In some individuals the stability either increased or decreased markedly during Kangaroo Care. The boys showed significantly less cardiorespiratory stability both during kangaroo care and in the incubator compared to the girls.

Female↗
PubMed1998

Clinical experience with heart transplantation in infants.

OBJECTIVE: Orthotopic heart transplantation has become an accepted therapeutic concept for adult patients with endstage heart disease. In newborns and infants this procedure is still a matter of discussion because of unknown long-term results and the lack of donor organs. METHODS: Since March 1988 we have performed 40 orthotopic heart transplantation in 39 infants who were from 1 to 280 days of age. Indications for transplantation included hypoplastic left-heart syndrome (n = 28), dilative cardiomyopathy (n = 4), endocardial fibroelastosis (n = 4) and other complex structural anomalies (n = 3). The mean waiting period for transplantation was 53 days. A donor-recipient weight ratio up to 4.0 was accepted. Profound hypothermic circulatory arrest was used for graft implantation in all those patients who required extensive aortic arch reconstruction (71%). The initial immunomodulation was based on Cyclosporine, Azathioprine and Prednisolone. Patients who underwent transplantation during the first 6 weeks of life received a chronic single-drug therapy with Cyclosporine after 1 year. RESULTS: There were six peri-operative deaths caused by drug-resistant right-heart failure in three cases, humoral rejection (n = 1), CMV infection (n = 1) and multi organ failure (n = 1). One infant died late, due to rejection. The actuarial survival rate for the entire group is now 82%. There is a remarkable influence of increasing experience. Whereas six of 15 infants who had heart transplantation between 1988 and 1993 died early post-operatively (survival rate: 60%), only one late death occurred among 24 recipients in the period from 1994 to April 1997 (survival rate: 96%). Episodes of rejection occurred once or several times in about half of the patients in this series (48%). All surviving children are living at home in excellent condition. CONCLUSIONS: Heart transplantation during early infancy is a rational and durable therapy for heart diseases with irreversible myocardial failure or severe structural anomalies. The intermediate-term results have been encouraging in many centers, but more data must be accumulated to determine the sequelae of chronic immunosuppression. The lack of donor organs remains one of the major problems in pediatric heart transplantation.

Body Height↗
PubMed1998

Intricate journey: the path of a manuscript from submission to publication.

This article traces the path of a manuscript that is submitted for publication consideration from the time of its receipt to its ultimate appearance in print. The peer review process is explained in detail. Though the process is similar for most journals, this article describes the process specific to the Journal of PeriAnesthesia Nursing.

Humans↗
PubMed1998

Superior caval venous syndrome after atrial switch procedure: relief of complete venous obstruction by gradual angioplasty and placement of stents.

Superior caval venous syndrome is one of the late problems known to occur after Mustard repair of complete transposition. Reoperation may leave residual stenosis, and carries substantial risk for the patient. It is now feasible to use intravascular stents to overcome systemic venous baffle obstructions, and such an approach is probably more effective. The purpose of our study therefore, was to assess immediate and medium term results of inserting stents subsequent to gradual balloon enlargement of acquired atresia of the intraatrial baffle in patients who had undergone an atrial switch operation. We investigated five patients with complete obstruction of the superior caval venous pathway at perforation of the atretic segment was achieved using a guide wire technique. The procedure was successful in all patients. Gradual angioplasty was performed and intravascular stents were implanted. The pressure in the superior caval vein dropped to normal values, symptoms improved, and the patency of the newly created venoatrial communication was proven at mid-term follow-up. Thus critical obstructions at the superior caval venous pathway after the Mustard procedure can be reopened by interventional catheterization. Implantation of balloon-expandable intravascular stents is safe and effective in the acute relief of the obstructions, but careful long-term follow-up is mandatory.

Adolescent↗
PubMed1998

Physiological characterisation of a pyruvate-carboxylase-negative Saccharomyces cerevisiae mutant in batch and chemostat cultures.

A prototrophic pyruvate-carboxylase-negative (Pyc-) mutant was constructed by deleting the PYC1 and PYC2 genes in a CEN.PK strain of Saccharomyces cerevisiae. Its maximum specific growth rate on ethanol was identical to that of the isogenic wild type but it was unable to grow in batch cultures in glucose-ammonia media. Consistent with earlier reports, growth on glucose could be restored by supplying aspartate as a sole nitrogen source. Ethanol could not replace aspartate as a source of oxaloacetate in batch cultures. To investigate whether alleviation of glucose repression allowed expression of alternative pathways for oxaloacetate synthesis, the Pyc- strain and an isogenic wild-type strain were grown in aerobic carbon-limited chemostat cultures at a dilution rate of 0.10 h-1 on mixtures of glucose and ethanol. In such mixed-substrate chemostat cultures of the Pyc- strain, steady-state growth could only be obtained when ethanol contributed 30% or more of the substrate carbon in the feed. Attempts to further decrease the ethanol content of the feed invariably resulted in washout. In Pyc- as well as in wild-type cultures, levels of isocitrate lyase, malate synthase and phospho-enol-pyruvate carboxykinase in cell extracts decreased with a decreasing ethanol content in the feed. Nevertheless, at the lowest ethanol fraction that supported growth of the Pyc- mutant, activities of the glyoxylate cycle enzymes in cell extracts were still sufficient to meet the requirement for C4-compounds in biomass synthesis. This suggests that factors other than glucose repression of alternative routes for oxaloacetate synthesis prevent growth of Pyc- mutants on glucose.

Ammonia↗
PubMed1998

Phase I clinical and pharmacokinetic study of the oral platinum analogue JM216 given daily for 14 days.

BACKGROUND: The oral bis (acetate) ammine dichloro cyclohexylamine platinum (IV) analogue (BMS-182751) was brought into clinical development because it was shown to be cytotoxic against some human tumour cell lines and to have an antitumor activity in murine tumours at least comparable to that of parenteral cisplatin and carboplatin. In early clinical studies in which the optimal schedule of treatment was daily for five consecutive days, dose-dependent nausea and vomiting occurred in about two-thirds of patients. PATIENTS AND METHODS: To evaluate if the use of lower daily doses for longer periods of time could result in a better tolerability, JM216 was given once daily for 14 consecutive days every four to five weeks to adult patients with solid tumors. Oral antiemetics were given prophylactically only at the highest doses. The pharmacokinetics of total and ultrafiltrable platinum were studied on days 1 and 14 of the first cycle by Inductively Coupled-Mass-Spectrometry (ICP-MS). RESULTS: Forty-six patients were treated at doses ranging from 10 mg/m2/d to 50 mg/m2/d and 39 were evaluable for hematologic toxicity over 74 cycles. MTDs were reached at 45 mg/m2/d and 50 mg/m2/d x 14 repeated every five weeks in patients with extensive, or limited/no prior treatment, respectively. The dose-limiting toxicity was neutropenia which was delayed and variable among patients. Other non-hematological toxicities were severe vomiting (22% of cycles), diarrhea (28% of cycles) and drug-associated fever (32% of patients), controlled with paracetamol. Subjective improvement with disappearance of tumour-related pain was observed in one patient with chemotherapy-resistant metastatic prostate cancer and in one previously untreated patient with malignant mesothelioma. Cmax and AUC values of both total and ultrafiltrable platinum on days 1 and 14 were highly variable among patients. Only Cmax on day 1 was linearly related to the dose. Total and ultrafiltrable platinum were still detectable two weeks after the last dose. No relationship could be established between AUC values and toxicities. CONCLUSIONS: Daily doses of JM216 of 40 mg/m2 and 45 mg/m2 for 14 consecutive days every five weeks with oral antiemetic prophylaxis are selected for phase II evaluation of single agent in patients with extensive or limited/no prior treatment, respectively. The administration of JM216 on a day x 14 schedule produced nausea and vomiting comparable to that observed with the day x 5 regimen but of longer duration. The variability of pharmacokinetics and pharmacodynamics, even though limited at the doses proposed for phase II evaluation of JM216 as single agent, recommend a careful monitoring of the patients.

Administration, Oral↗