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Biomedical subjects

B Maier

Publications and source records attributed to B Maier.

At least 37 records · Page 2Linked to original sources

Megaprosthetic replacement of the pelvis: function in 17 cases.

Between 1980 and 1997, we treated 39 patients (mean age 39 (16-66) years, 24 men) with megaprosthetic replacement of a large bone defect (> 10 cm) of the pelvis. The bone resection was necessary in 38 cases due to malignant bone and soft tissue tumors and in 1 case due to hydatid disease. Polyacetal hemipelvic replacement was performed in 29 cases, CAD hemipelvic replacement in 8 cases, and a saddle prosthesis was inserted in 2 cases. All patients were followed clinically and radiographically. The mean follow-up was 58 (15-110) months. 20 patients have died of their tumor. 10 local infections occurred, in 2 cases necessitating hemipelvectomy. Hip dislocation occurred in 6 cases. 13 of the remaining 17 survivors had good or excellent clinical results according to the Enneking evaluation (MSTS). In 6 of the 17 survivors, radiographs revealed implant loosening.

Adolescent↗

Improving the care of cardiothoracic surgery patients through advanced nursing skills.

All the nurses in the cardiothoracic ICU are now certified in these advanced skills. The skills are reviewed with current staff members on a yearly basis during the annual evaluation. During their orientation to the cardiothoracic ICU, new staff nurses are certified by using the original process of attending an in-service training program and demonstrating the skill 3 times. The quality management department reviews medical records daily to detect complications. In addition, we (DRZ and MB) conducted a quality assurance review in which we monitored 20 patients being extubated and having PA catheters removed by nurses. No complications were noted during either review. The institution has seen improvements in quality of care and earlier discharge from the hospital. With earlier removal of endotracheal tubes and PA catheters, patients are more comfortable and their rehabilitation can be advanced sooner. Comparison of the mean length of stay for patients undergoing coronary artery bypass graft in March 1995 with the mean length of stay for such patients in March 1998 showed a 50.6% decrease, from 14.94 days to 7.38 days. These advanced skills have provided an increased autonomy for the nurses and have benefited the patients undergoing cardiac surgery in our institution.

Cardiac Surgical Procedures↗

[Chronic pelvic pain--a still too little appreciated disease picture].

Chronic pelvic pain often means for patients as well as for their physicians a dilemma concerning diagnosis and therapy: the common medical approach does often not fit for essential therapeutic needs, which should include somatic examination as well as psychosomatic (psychotherapeutic) concepts for escaping from further somatic chronification typical for CPP-patients. The study performed during 1995-98 with 220 patients of the Department of Obstetrics & Gynecology in collaboration with the Psychosomatic Department in the St. Johann's Hospital of Salzburg has shown results about laparoscopic/pelviscopic and psychosomatic interventions in patients with chronic pelvic pain. Evidence-based somatic medicine is not able to explain the discrepancy between pathomorphology and intensity of pain in CPP-patients. The specific dilemma in treating CPP-patients could be characterized as the following: Somatisation is often the one and only symptom presented by CPP-patients to gynecologists. It is the physician's task to stay in a relationship with the patient and treat her symptomatically on somatic symptoms. The relationship will provide the chance to introduce a psychosomatic approach and engage psychotherapeutic work on the reluctance of accepting a psychogenesis of CPP. Gynecologists lack psychosomatic knowledge and concepts for treatment and therefore often contribute to the chronification of CPP in patients approached only in somatic terms.

Chronic Disease↗

Post-transcriptional regulation of neurofibromin level in cultured human melanocytes in response to growth factors.

Among the symptoms that characterize neurofibromatosis type 1 (NF1) are pigmentation anomalies such as cafe au lait spots. It has been suggested that the reduction of the neurofibromin level in the epidermis of NF1 patients is responsible for the observed signs such as altered melanogenesis and altered density of melanocytes. Our studies show that in cultured normal human melanocytes, the neurofibromin level can be varied in vitro over a wide range by using different culture conditions. The influence of factors that control differentiation and proliferation of melanocytes on neurofibromin levels was studied. Immunoprecipitation followed by western blotting showed a 3- to 4-fold increase of neurofibromin after stimulation by PMA or bFGF, respectively, and a 1.5-fold increase in cells stimulated with steel factor. The increase of neurofibromin was not paralleled by a higher NF1 mRNA level as proved by northern blotting. Pulse-chase experiments with 35S-labeled melanocytes revealed an approximately 3-fold increase in the half-life of neurofibromin in bFGF- or PMA-stimulated cells compared to controls. These results indicate that the neurofibromin level of cultured melanocytes can be regulated by a mechanism independent of NF1 gene transcription and translation, which might influence the degradation rate of the protein.

Cells, Cultured↗

Clinical pathways and coronary artery bypass surgery.

Use of a multidisciplinary clinical pathway helps eliminate variations in patients' care. Organizing the care delivered each day of the patient's hospitalization may lead to fewer complications, a quicker recovery, and an earlier discharge. In today's healthcare arena, much attention is being focused on improving the quality of care and decreasing the need for acute care. Clinical pathways facilitate patients' outcomes and earlier discharge and thus reduce the cost of care.

Adult↗

Dynamics of viral variants in HIV-1 Nef and specific cytotoxic T lymphocytes in vivo.

The vigorous CTL response directed against HIV is considered to be important in reducing HIV viral load, although it is unable to stop ongoing viral replication, which generates new antigenic variants. We analyzed the impact of sequential changes in five epitopes of HIV-1 Nef on CTL recognition in four stable patients. A high rate of variation was found, and in all these patients we could detect CTL specific for 32 out of 36 autologous viral variants occurring in 5 HLA-A2- or HLA-B7-restricted Nef epitopes at two time points. Two distinct patterns for dynamics of CTL responses to viral variation were observed: 1) temporary amplification of viral variants followed by expansion of variant-specific CTL, ultimately leading to the disappearance of 12 out of the 14 initial epitope variants within two years. A second set of viral variants that had replaced the initial ones could also stimulate specific CTL precursors in the context of the same or an alternative HLA molecule; and 2) persistence of 2 viral variants in relatively conserved epitopes despite specific CTL recognition. Therefore, a remarkable flexibility of the immune system allows constant adaptation of CTL to multiple HIV variants and thus elimination of HIV variant-producing cells in slow progressors.

Amino Acid Sequence↗

[Combined "3-in-1"/sciatic nerve block. Block effectiveness, serum level and side effects using 700 mg mepivacaine 1% without and with adrenaline and prilocaine 1%].

UNLABELLED: A high dose of local anaesthetic is necessary for the combined "3-in-1"/sciatic nerve block. Prilocaine is recommended for its low toxicity. However, in some patients prilocaine results in pronounced methaemoglobin formation due to toludine. Little has been known hitherto about the use of high-dose mepivacaine for the combined 3-1/sciatic nerve block. This study was undertaken to compare the use of 700 mg mepivacaine 1% and of 700 mg prilocaine 1%. METHODS: The study was approved by the ethics committee of our hospital. Once their informed consent had been obtained in writing 3 x 20 patients (ASA 1-2) undergoing planned surgery on the foot or ankle joint were enrolled in the study. The patients were randomized to the following three groups on a double-blind basis: group 1,700 mg mepivacaine without epinephrine; group 2,700 mg mepivacaine with 0.2 mg epinephrine (1:350,000); group 3,700 mg prilocaine 1%. Arterial blood samples for determination of local anaesthetic serum levels were collected over a 120-min period. We determined methaemoglobin and oxygen saturation before and 120 min after the blockade and continued these measurements for 6 h in group 3. At 15-min intervals, all patients were questioned about early signs of toxicity. The perioperative monitoring including blood pressure, ECG and pulse oximetry. Data were analysed using ANOVA and Student's t-test, P < 0.05 considered statistically significant. RESULTS: The blocking efficacy did not differ among the groups (groups 1, 2, 3:90%, 95%, 90%). The maximum mepivacaine serum level in group 1 was 3.91 micrograms/ml +/- 0.95 and 2.94 micrograms/ml +/- 0.58 in group 2 (Fig. 2). Over the entire observation period the addition of epinephrine resulted in a significant reduction of the serum level (between 60.3% at t = 15 min and 19.7% at t = 120 min). In the prilocaine group the maximum serum level was 2.07 micrograms/ml +/- 0.56, significantly less than in either mepivacaine group. No patient showed signs or symptoms of local anaesthetic toxicity. In the prilocaine group there was wide variation in methaemoglobin formation among the patient, with a median of 10.1% (Fig. 3, Table 3). Three patients showed a maximum methaemoglobinemia between 16% and 17%. Five patients were still cyanotic after 6 h when they were transferred to the ward. The fractional SaO2 values amounted to 88% (median) with a minimum of 80.3%. CONCLUSION: Both mepivacaine 1% and prilocaine 1% are appropriate local anaesthetics for the combined 3-in-1/sciatic nerve block at a dose of 700 mg. There was no difference in the blocking efficacy. No patient showed clinical signs or symptoms of a local anaesthetic toxicity. Following prilocaine we are sometimes faced with high methaemoglobinemia, which may necessitate prolonged monitoring.

Adult↗

Human immune response to HIV-1 Nef. II. Induction of HIV-1/HIV-2 Nef cross-reactive cytotoxic T lymphocytes in peripheral blood lymphocytes of non-infected healthy individuals.

HIV-specific CD8+ cytotoxic T lymphocytes (CTL) are thought to have a beneficial role in HIV infection. In a previous report we have shown that HIV-1 Nef-specific CTL can be readily induced in peripheral blood lymphocytes of seronegative healthy young adults by in vitro stimulation with autologous Epstein-Barr virus-transformed B lymphoblastoid cell lines transfected with the HIV-1 nef gene. Here we demonstrate that these Nef-specific CTL can efficiently lyse HIV-infected primary CD4+ T lymphocytes. CTL of the blood donor tested were Nef-specific and restricted by the autologous MHC class I molecules HLA-A2 and HLA-B7. They recognized HIV-1 Nef in association with both restriction elements but HIV-2 Nef only in association with HLA-B7. The cross-reactivity of the induced effector cells together with the potent immunogenicity of Nef in healthy seronegatives further support the inclusion of Nef as a constituent of HIV vaccines.

B-Lymphocytes↗

Sequence constraints and recognition by CTL of an HLA-B27-restricted HIV-1 gag epitope.

Previous studies on the variation of an immunodominant HLA-B27-restricted HIV-1 gag p24 epitope (KRWIIL GLNK, amino acids 263-272) have demonstrated the persistence of variants recognized by CTL. Sequence comparisons of HIV isolates showed that this region is relatively conserved and as a consequence might restrict antigenic variation. To evaluate the possibility of HIV-1 to yield infectious mutants of this epitope that lack the ability to bind to HLA-B27 or escape HLA-B27-restricted CTL recognition, single-point mutations were constructed in the infectious molecular clone of HIV-1 Lai. Changes of arginine 264, the anchor amino acid for HLA-B27, to lysine or glycine resulted in infectious HIV-1 variants. The respective synthetic peptides showed reduced ability to sensitize target cells for CTL recognition and a corresponding loss of binding affinity to HLA-B27. In contrast, mutation of glycine 269 to lysine or glutamate abrogated HIV-1 infectivity. The corresponding peptides were able to bind to HLA-B27 but were not recognized by CTL. These data show that HIV-1 tolerates some genetic variation of the HLA-B27-restricted CTL epitope in gag p24 and that single-point mutations can alter quantitatively the immunologic properties. Further, it demonstrates that the mere nonrecognition of peptides derived from quasispecies analysis of small regions might simply correspond to nonviable virus variants and cannot be taken as evidence for CTL escape mutants. Together with the previously published data on the persistence of CTL epitopes, these results suggest that CTL do not play a major role in driving HIV-1 evolution in vivo.

Amino Acid Sequence↗

Contribution of proteasome-mediated proteolysis to the hierarchy of epitopes presented by major histocompatibility complex class I molecules.

Major histocompatibility complex (MHC) class I-restricted cytotoxic T lymphocytes (CTL) recognize peptide epitopes of protein antigens in a hierarchical fashion. We investigated whether proteolytic cleavage, in particular by proteasomes, is important in determining epitope hierarchy. Using highly purified 20S proteasomes, we find preferred cleavage sites directly adjacent to the N- and C-terminal ends of the immunodominant epitope of chicken ovalbumin, Ova257-264, while most of the subdominant epitope, Ova55-62, is destroyed by a major cleavage site located within this epitope. Moreover, we show that variations in amino acid sequences flanking these epitopes influence proteasomal cleavage patterns in parallel with the efficacy of their presentation. The results suggest that proteasomal cleavage within and adjacent to class I-restricted epitopes contributes to their level of presentation.

Amino Acid Sequence↗

[Pacemaker therapy for the sick sinus node syndrome. Does the atrially involved pacemaker system lower the frequency of atrial fibrillation and thromboembolic complications as well as mortality?].

Between 1986 and 1992, pacemakers were implanted in 307 patients with symptoms caused by the sick sinus syndrome (SSS). 301 patients were regularly followed up (161 men, 146 women, mean age 72.9 [27-91] years) of whom 180 had a VVI, 65 and AAI and 58 a DDD/DDI pacemaker. Mean follow-up period was 58.3 months for VVI-stimulated patients and 35.6 months for atrial paced patients. The data were analysed retrospectively to ascertain whether a change in pacemaker treatment to a more physiological system produced any lowering in the mortality rate, incidence of permanent atrial fibrillation (AF), and thromboembolic phenomena. The annual mortality rate of the VVI-stimulated patients was 6.9%, that of atrial paced patients 2.8%. Age, abnormal ventricular function, survived resuscitation and diabetes mellitus each correlated with a shortened life expectancy already at the time of implantation, regardless of the pacemaker mode. Permanent AF was more frequent during VVI stimulation (16% vs 7%), especially if it had been preceded by intermittent AF (26% vs 13%). But there was no significant difference with regard to transitory cerebral ischaemic episodes and peripheral arterial emboli (15% vs 10%). Fewer patients with atrial pacing went into heart failure (20% vs 30%). Four patients developed a high-grade atrioventricular (a-v) block on AAI stimulation (annual incidence 2.4%). - These observations suggest that patients with SSS should always have atrial paced pacemaker systems. If a-v conduction is disturbed, a bifocal pacemaker is the system of choice.

Adult↗

Human immune response to HIV-1-Nef. I. CD45RO- T lymphocytes of non-infected donors contain cytotoxic T lymphocyte precursors at high frequency.

The immune response of peripheral blood lymphocytes (PBL) of non-exposed human individuals to the Nef protein of HIV-1 was studied. Nef is a regulatory protein of HIV which is immediately expressed after infection and which seems to be important in the pathogenicity of HIV. Nef may therefore serve as a potential target for effective immunity against HIV infection. Epstein-Barr (EBV)-transformed lymphoblastoid B cell lines (LCL) were established from four healthy young seronegative adults and transfected with the Nef gene. These cells served as stimulator cells for autologous PBL in vitro and as target cells for CTL. CTL responses were readily generated against Nef-transfected LCL, consisting of Nef-specific and putative EBV-specific CTL. Nef-specific CTL were generated exclusively from CD8+ cells and were MHC class I restricted. Since a vigorous Nef-specific CTL response in non-infected individuals was unexpected, CTL precursor frequencies were determined by limiting dilution analyses in non-fractionated PBL and in PBL separated into the CD45RO- (naive) and CD45RO+ (memory) T cell populations. As expected, the putative EBV-specific CTL precursors were predominantly found in the CD45RO+ subset at frequencies typical for memory T cells. Nef-specific CTL precursors, in contrast, were found predominantly in the CD45RO- population, at even higher frequencies of approximately 1/1000-1/3000. Nef may thus display either an unusually high number of immunogenic peptides or a limited number of peptides presented in a very efficient way, so that many T cells including low affinity cells, would be triggered.

Adult↗