Biomedical subjects

J Bauer

Publications and source records attributed to J Bauer.

At least 199 records · Page 11Linked to original sources

PubMed1998

Structure-activity relationship of synthetic phosphoinositolglycans mimicking metabolic insulin action.

Phosphoinositolglycan (PIG) molecules have been implicated to stimulate glucose and lipid metabolism in insulin-sensitive cells and tissues in vitro and in vivo. The structural requirements for this partial insulin-mimetic activity remained unclear so far. For establishment of a first structure-activity relationship, a number of PIG compounds were synthesized consisting of the complete or shortened/mutated glycan moiety derived from the structure of the glycosylphosphatidylinositol (GPI) anchor of the GPI-anchored protein, Gce1p, from yeast. The PIG compounds were divided into four classes according to their insulin-mimetic activity in vitro with the typical representatives: compound 41, HO-SO2-O-6Manalpha1(Manalpha1-2)-2Manalpha1 (6-HSO3)- -6Manalpha1-4GluNb eta1-6(D)inositol-1,2-(cyclic)-phosphate; compound 37, HO-PO(H)O-6Manalpha1(Manalpha1-2)-2Manalpha1-6Manal pha1-4GluNbeta1-6( D)inositol-1,2-(cyclic)-phosphate; compound 7, HO-PO(H)O-6Manalpha1-4GluN(1-6(L)inositol-1,2-(cyclic)-ph osp hate; and compound 1, HO-PO(H)O-6Manalpha1-4GluN(1-6(L)inositol. Compounds 41 and 37 stimulated lipogenesis up to 90% (at 20 microM) of the maximal insulin response but with differing concentrations required for 50% activation (EC50 values 2.5 +/- 0.9 vs 4.9 +/- 1.7 microM) as well as glycogen synthase (4.7 +/- 1 vs 9.5 +/- 1.5 microM) and glycerol-3-phosphate acyltransferase (3.5 +/- 0.8 vs 8.0 +/- 1.1 microM). Compound 7 was clearly less potent (20% of the maximal insulin response at 100 microM), whereas compound 1 was almost inactive. This relative ranking in the insulin-mimetic potency between members of the PIG classes (e.g., 41 > 37 >> 7 > 1) was also observed for the (i) activation of glucose transport and glucose transporter isoform 4 translocation in isolated normal and insulin-resistant adipocytes, (ii) inhibition of lipolysis in adipocytes, (iii) stimulation of glucose transport and glycogen synthesis in isolated normal and insulin-resistant diaphragms, and (iv) induction of tyrosine phosphorylation of insulin receptor substrate-1 (IRS-1) in diaphragms. The complete glycan core structure (Man3-GluN) of typical GPI anchors including a mannose side chain and the inositolphosphate moiety was required for maximal insulin-mimetic activity of the PIG compounds with some variations possible with respect to the type of residues coupled to the terminal mannose/inositol as well as the type of linkages involved. These data argue for the potency and specificity of the interaction of PIG molecules with putative signaling component(s) (presumably at the level of the IRS proteins) in adipose and muscle cells which finally lead to insulin-mimetic metabolic activity even in insulin-resistant states.

Adipocytes↗

PubMed1998

B lymphocytes producing demyelinating autoantibodies: development and function in gene-targeted transgenic mice.

We studied the cellular basis of self tolerance of B cells specific for brain autoantigens using transgenic mice engineered to produce high titers of autoantibodies against the myelin oligodendrocyte glycoprotein (MOG), a surface component of central nervous system myelin. We generated "knock-in" mice by replacing the germline JH locus with the rearranged immunoglobulin (Ig) H chain variable (V) gene of a pathogenic MOG-specific monoclonal antibody. In the transgenic mice, conventional B cells reach normal numbers in bone marrow and periphery and express exclusively transgenic H chains, resulting in high titers of MOG-specific serum Igs. Additionally, about one third of transgenic B cells bind MOG, thus demonstrating the absence of active tolerization. Furthermore, peritoneal B-1 lymphocytes are strongly depleted. Upon immunization with MOG, the mature transgenic B cell population undergoes normal differentiation to plasma cells secreting MOG-specific IgG antibodies, during which both Ig isotype switching and somatic mutation occur. In naive transgenic mice, the presence of this substantial autoreactive B cell population is benign, and the mice fail to develop either spontaneous neurological disease or pathological evidence of demyelination. However, the presence of the transgene both accelerates and exacerbates experimental autoimmune encephalitis, irrespective of the identity of the initial autoimmune insult.

Amino Acid Sequence↗

PubMed1998

NF-kappaB modulates lipopolysaccharide-induced microglial nerve growth factor expression.

Microglia/brain macrophages activated in response to injury, infection, or inflammation of the central nervous system (CNS) mediate both neurotoxic and neurotrophic activities. Although the cytotoxic effects of microglia have been analyzed in detail, little is known about the signaling pathways involved in microglial neurotrophin expression. Using purified rat microglial cell cultures, the effects of inflammatory agents such as lipopolysaccharide (LPS) on microglial nerve growth factor (NGF) expression were studied. Application of LPS (0.1-100 ng/ml) induced a rapid (2-4 h), dose-dependent increase in NGF mRNA expression followed by enhanced release of NGF protein within 24 h. To determine whether the transcription factor NF-kappaB, known to be stimulated in activated microglia, is involved in inflammatory mediator-induced NGF expression, we used the NF-kappaB inhibitor pyrrolidine dithiocarbamate (PDTC). Addition of PDTC (100 microM) to microglia completely abolished LPS-induced NGF synthesis, suggesting a key role for NF-kappaB in microglial NGF expression by inflammatory mediators. In conclusion, NF-kappaB-controlled NGF expression by activated microglia appears to contribute to the cross-talk between the immune and nervous systems during inflammation in the CNS.

Animals↗

PubMed1998

Counterbalancing hydrodynamic sample distortion effects increases resolution of free-flow zone electrophoresis.

On fractionation of highly heterogeneous protein mixtures, optimal resolution was achieved by forcing proteins to migrate through a preestablished pH gradient, until they entered a medium with a pH similar but not equal to their pIs. For this purpose, up to seven different media were pumped through the electrophoresis chamber so that they were flowing adjacently to each other, forming a pH gradient declining stepwise from the cathode to the anode. This gradient had a sufficiently strong band-focusing effect to counterbalance sample distortion effects of the flowing medium as proteins approached their isoelectric medium closer than 0.5 pH units. Continuous free-flow zone electrophoresis (FFZE) with high throughput capability was applicable if proteins did not precipitate or aggregate in these media. If components of heterogeneous protein mixtures had already started to precipitate or aggregate, in a medium with a pH exceeding their pI by more than 0.5 pH units, the application of interval modus and media forming flat pH gradients appeared advantageous.

Buffers↗

PubMed1998

The importance of fiber biopersistence and lung dose in determining the chronic inhalation effects of X607, RCF1, and chrysotile asbestos in rats.

The chronic inhalation effects in rats of X607 (a rapidly dissolving synthetic vitreous fiber) were compared with those previously reported for RCF1 (a refractory ceramic synthetic vitreous fiber) and chrysotile asbestos. Of primary concern was the importance of biopersistence as a mechanism of fiber toxicity. Fischer rats were exposed to fiber aerosol by nose-only inhalation for 6 h/day, 5 days/week for 2 years. X607 and RCF1 aerosols were similar in concentration (approximately 200 fibers/cc) and average dimensions (approximately 20 x 1 microns). Chrysotile aerosol was higher in concentration (10,600 fibers/cc) and an order of magnitude smaller in average dimensions. Lung fiber deposition after 6 h inhalation was greater for X607 than for RCF1. However, at later time points, fibers/lung (especially long fibers) were much lower for X607 than for RCF1, suggesting less biopersistence for X607. X607 was neither fibrogenic nor tumorigenic and induced only minimal lung cellularity that reversed after exposure was terminated. In contrast, RCF1 and chrysotile asbestos induced pulmonary fibrosis and thoracic neoplasms (chrysotile induced 32% more pulmonary neoplasms than RCF1). Lung deposition and fiber lengths did not explain the toxicologic differences between the three fibers. Fiber biodurability, including chemical and physical parameters, appears to be a major toxicologic determinant here. Chemical analysis of lung fibers revealed rapid leaching of X607 compared to RCF1. In in vitro dissolution tests, X607 underwent rapid dissolution (kdis = 990 ng/cm2/h) and transverse fragmentation, RCF1 dissolved slowly (kdis = 6 ng/cm2/h) and did not fragment, and chrysotile dissolution was negligible (< 0.1 ng/cm2/h).

Animals↗

PubMed1998

[Scleredema adultorum Buschke. Case report and review of the literature].

Scleredema adultorum of Buschke is a rare disorder of unknown aetiology. It is characterized by diffuse, non-pitting swelling and induration of the skin. Skin biopsies reveal marked thickening of the dermis due to collagenous replacement of the subcutis and deposition of hyaluronic acid between the collagen fibers. The disease classically only affects the skin. In 24 cases an associated monoclonal gammopathy has been detected. A 75-year-old patient had a 19-year history of scleredema adultorum. In addition to a monoclonal gammopathy the patient suffered from involvement of the tongue, pharynx and upper esophagus. Furthermore a polyneuropathy, ocular involvement with restricted eye movements and a sicca syndrome were present. The simultaneous occurrence of cutaneous scleredema with any one of the above mentioned symptoms has been reported before. The wide variety of extracutaneous manifestations of scleredema as found in our patient is amazing and has not been previously described.

Aged↗

PubMed1998

[Asystolic seizures].

Epileptic seizures may alter autonomic functions. This is especially the case with complex focal seizures (of temporal lobe origin) and grand mal. Most frequently, such seizures cause ictal tachycardia, sometimes tachypnea, probably caused by the propagation of epileptic discharges to autonomic cerebral structures. Ictal bradycardia and asystole are rare phenomena. However, they may be life threatening. Their differentiation from primary cardiac arrest is possible by the use of ictal EEG and ECG registration. Postictal serum prolactin measurement does not differentiate syncope from seizure. However, a postictal increase of creatine kinase is only measured after epileptic seizures and not after syncope. Treatment of such epileptic seizures includes an optimization of anticonvulsant drug therapy and the implantation of a cardiac demand stimulator. There is growing evidence that ictal asystole is a cofactor in sudden unexplained death in epileptic patients.

Adult↗

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↗