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Biomedical subjects

M Kaufmann

Publications and source records attributed to M Kaufmann.

At least 235 records · Page 13Linked to original sources
PubMed1993

Cerebrovascular carbon dioxide reactivity during exposure to equipotent isoflurane and isoflurane in nitrous oxide anaesthesia.

We have studied the effects of hypocapnia on cerebrovascular changes in two MAC-equivalent anaesthetic regimens, using the transcranial Doppler technique as an index of cerebral blood flow (CBF) in 24 healthy ASA I patients undergoing spinal surgery. Eight of the patients were subjected to carbon dioxide reactivity challenges in the awake state. Before surgery, the other 16 patients received, in random order, either 1.15% isoflurane in oxygen or 0.5% isoflurane with 70% nitrous oxide. Carbon dioxide reactivity was calculated for each group as the increase in flow velocity per kPa change in PE'CO2 (cm s-1 kPa-1). It was significantly greater for the isoflurane group (14.09 (SD 2.44) cm s-1 kPa-1) and significantly less for the isoflurane-nitrous oxide group (7.95 (1.32) cm s-1 kPa-1) compared with the awake group (11.24 (0.95) cm s-1 kPa-1). We conclude that cerebrovascular responsiveness to changes in arterial carbon dioxide concentration is influenced markedly by the anaesthetic procedure. Hyperventilation is more likely to affect CBF during isoflurane anaesthesia than during an MAC-equivalent isoflurane-nitrous oxide anaesthesia.

Adult↗
PubMed1993

Asynchronous increases in oxidative capacity and resistance to fatigue of electrostimulated muscles of rat and rabbit.

1. The present study investigates to what extent increases in resistance to fatigue and aerobic oxidative capacity of energy metabolism are correlated in fast-twitch tibialis anterior muscles of rat and rabbit subjected to chronic low-frequency stimulation. 2. Changes in the aerobic oxidative capacity of the stimulated muscles were judged from increases in citrate synthase activity, representing the constant-proportion enzyme group of the citric acid cycle. 3. Resistance to fatigue reached maximal values in both rat and rabbit tibialis anterior muscles after stimulation periods of 14 days, whereas citrate synthase activity continued to increase with longer stimulation periods. 4. Different time courses of the changes in resistance to fatigue and citrate synthase activity were observed not only with prolonged stimulation periods but also during the first week, when pronounced increases in resistance to fatigue were accompanied by only moderate elevations in citrate synthase activity. 5. The dissociation between the changes of the two parameters studied suggests that factors other than elevated aerobic oxidative capacity contribute to enhanced resistance to fatigue.

Adaptation, Physiological↗
PubMed1993

Adjuvant randomized trials of doxorubicin/cyclophosphamide versus doxorubicin/cyclophosphamide/tamoxifen and CMF chemotherapy versus tamoxifen in women with node-positive breast cancer.

PURPOSE: We report two randomized trials of adjuvant systemic therapy in 747 patients < or = 65 years of age with histologically proven node-positive breast cancer. PATIENTS AND METHODS: Patients were selected for the two trials on the basis of lymph node and hormone receptor status. The only stratification was based on the treating institution. In patients with a lower probability of recurrence (n = 276), a comparison between endocrine therapy (tamoxifen [Tam] 30 mg/d for 2 years) and chemotherapy (cyclophosphamide, methotrexate, and fluorouracil [CMF] intravenously [IV], six cycles every 4 weeks) was performed. In patients with a higher risk of recurrence (n = 471), a comparison between chemotherapy alone (doxorubicin plus cyclophosphamide [AC] i.v., eight cycles every 3 weeks) and the same chemotherapy plus Tam was made. RESULTS: Overall, we found that CMF and Tam are equally effective in a subgroup of patients with a relatively good prognosis (low-risk patients). However, in the subset of women < or = 49 years old, a significantly greater disease-free survival (DFS) rate (P = .01) and overall survival (OS) rate (P = .002) was observed following therapy with CMF compared with Tam. In patients > or = 50 years old, the opposite was found, and Tam appeared to be superior to CMF (DFS, P = .003; OSm P = .5). These results must be interpreted cautiously, since a post-hoc stratification of patients by age (< or = 49, > or = 50) was performed, and significantly more younger, low-risk patients were randomized to receive chemotherapy alone and more older patients to receive Tam alone. Among patients with a relatively poor prognosis (high-risk patients), a combination of AC plus Tam was equivalent to AC and, when women were analyzed by age, this was found to be true of patients < or = 49 years as well. However, the addition of Tam to AC in women age > or 50 years resulted in a statistically significantly higher DFS (P = .01) and a trend toward better OS compared with women who received AC alone. CONCLUSION: Further trials are required to analyze the role of combined simultaneous or sequential chemoendocrine adjuvant treatment or each single therapy alone in defined risk-adapted subsets of node-negative and node-positive patients.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1993

Cleavage of human and mouse cytoskeletal and sarcomeric proteins by human immunodeficiency virus type 1 protease. Actin, desmin, myosin, and tropomyosin.

HeLa cell actin was cleaved by human immunodeficiency virus type 1 protease when in its soluble, globular form (G-actin). No cleavage of the polymerized, filamentous form of actin (F-actin) was observed when examined by denaturing gel electrophoresis; however, electron microscopy revealed a low level of cleavage of F-actin. Immunoblotting of mouse skeletal and human pectoral muscle myofibrils treated in vitro with human immunodeficiency virus type 1 protease showed that myosin heavy chain, desmin, tropomyosin, and a fraction of the actin were all cleaved. Electron microscopy of these myofibrils demonstrated changes consistent with cleavage of these proteins: Z-lines were rapidly lost, the length of the A bands was shortened, and the thick filaments (myosin filaments) were often laterally frayed such that the structures disintegrated. Nonmuscle myosin heavy chains were also cleaved by this enzyme in vitro. These data demonstrate that this protease can cause alterations in muscle cell ultrastructure in vitro that may be of clinical relevance in infected individuals.

Actins↗
PubMed1992

The principal neutralization determinant of simian immunodeficiency virus differs from that of human immunodeficiency virus type 1.

To identify the principal neutralization determinant (PND) of simian immunodeficiency virus (SIV), antisera were generated using recombinant gp110 [the SIV analog of the human immunodeficiency virus type 1 (HIV-1) external envelope glycoprotein, gp120], gp140, several large recombinant and proteolytic envelope fragments, and synthetic peptides of the SIVmac251 isolate. When purified under conditions that retain its native structure, gp110 bound CD4 and elicited antisera that neutralized SIVmac251 with high titer. Native gp110 also completely inhibited neutralizing antibody in sera from SIVmac251-infected macaques. In contrast, denatured gp110 and gp140, large envelope fragments, and synthetic peptides (including peptides analogous to the HIV-1 PND) elicited very low or undetectable neutralizing antibody titers and did not inhibit neutralizing antibody in infected macaque sera. Enzymatically deglycosylated gp110 efficiently absorbed neutralizing antibodies from macaque sera, showing that neutralizing antibodies primarily bind the protein backbone. A 45-kDa protease digest product, mapping to the carboxyl-terminal third of gp110, also completely absorbed neutralizing antibodies from infected macaque sera. These results show that the PND(s) of this SIV isolate depends on the native conformation and that linear peptides corresponding to the V3 loop of SIV envelope, in contrast to that of HIV-1, do not elicit neutralizing antibody. This may affect the usefulness of SIVmac for evaluating HIV-1 envelope vaccine approaches that rely on eliciting neutralizing antibody.

Antigens, Viral↗
PubMed1992

Goserelin depot in the treatment of premenopausal advanced breast cancer.

333 pre- and peri-menopausal patients with breast cancer entered a programme of open studies on the effect of goserelin. Of the 333 patients, 265 patients were entered into assessable efficacy studies. Efficacy data were analysed from 228 eligible patients receiving 3.6 mg of goserelin administered as a subcutaneous injection of a depot formulation once every 28 days. Mean serum luteinising hormone (LH) and oestradiol concentrations were suppressed by day 22 after the first injection. Subjective response occurred in 68.3% of patients assessed. Objective response (UICC criteria) occurred in 36.4% of patients and the lifetable median duration of response was 44 weeks. Responses were observed in all histological grades of tumour, and regardless of oestrogen receptor status. Treatment was well tolerated with no withdrawals due to possible adverse reactions of which hot flushes (75.9%) and loss of libido (47.4%) were commonly encountered. Goserelin provides an effective well tolerated medical alternative to ovarian ablation in the management of advanced breast cancer.

Adult↗
PubMed1992

[Three-dimensional ultrasound imaging of benign and malignant breast tumors--initial clinical experiences].

Previous experimental and clinical studies showed, that three-dimensional (3-D), i.e. dynamic spatial reconstruction of 2-D ultrasound images is feasible. A rotating acoustic plane helps to visualise the cross-sections serially and in a coordinated manner. When reconstructing the 2-D ultrasound images, surface reconstruction from planar contours of each cross-section is performed (so that the organ limits are defined) and the cross-sectional pictures are reconstructed into 3-D organ images. This approach had been described by the authors on a previous occasion. Another step forward is "transparent" spatial imaging eliminates the source of error involved in contouring. It is important to emphasise, that the 3-D system now described by the authors, yields a spatial image of the organ in question, and does not just present 3 planes of the organ (some authors have been claiming, that such an imaging method is also three-dimensional). Our system enables the imaging of several cross-sectional planes cut through the spatially calculated organ. This results in cross-sections, which cannot be performed by conventional sonography, thus disclosing new perspectives and possibilities. In the present article, the authors describe a clinical pilot study in the diagnosis of carcinomas of the breast. In our opinion, 3-D imaging of the tumours enables the physician to diagnose the status of the tumours; this is demonstrated by the examples of 35 malignant and benign tumours of the breast. In 95% of the cases of malignant tumours and 80% of the benign tumours, the diagnosis proved correct. This paper describes the fundamental possibilities and limitations of the new method.

Breast Neoplasms↗
PubMed1992

[B-streptococci in obstetrics--risks and consequences of maternal colonization and neonatal contamination].

2,373 mothers and their newborn were studied during two years with respect to B streptococci colonisation or contamination. Bacteriological, vaginal and anal smears were taken from mothers at the beginning of parturition, as well as the amnion and the aspirated stomach contents of the newborn, employing, in each case, conventional culture methods and a latex agglutination test as a rapid testing method. Smears from the ears were also taken from the newborn for bacteriological examination. The vertical transmission and its possible influencing variables were examined in 1,328 mother/child pairs of the first observation year. Surface contamination of the newborn was confirmed in 10% in at least one smear. In the group of mothers with B streptococci colonisation, the amnion showed the highest rate of contamination (43%), followed by the aspirated stomach contents (26%) and the ear smears (taken from each side separately) with 28% and 30% respectively. Vertical transmission was decisively influenced by vaginal maternal colonisation (50% of the cases resulting in contamination of newborn), whereas anal colonisation, if it was the only site of colonisation, resulted in contamination of newborn in only 32% of the cases. The rate of contamination of newborn dropped significantly from 50% to 20% after intrapartal antibiotic prophylaxis, the latter appearing to be meaningful only after at least 6 hours of exposure. In this group, the surface contamination could be reduced from 61% to 8%. A group of newborn suffering from early onset of sepsis (0.4%), was compared with a group of 13 newborn at risk of infection (0.9%) with established surface contamination and clinical or laboratory chemistry confirmation of infection.(ABSTRACT TRUNCATED AT 250 WORDS)

Ampicillin↗
PubMed1992

[Ultrasound diagnosis of blood flow in benign and malignant breast tumors].

Malignant tumours can be differentiated from the benign ones by their vascular blood supply. We employed three methods to analyse the blood flow: the angiodynograph, the duplex system, and the continuous-wave Doppler method, and measured the blood flow in 151 patients on the preoperative day. Histology revealed a malignoma in 92 cases and a benign tumour in 59 cases. It was found, that in more than 90% of the malignomas, a high blood flow was identified in or around the tumour by means of the colour method (angiodynography), which could be quantified by the pulsed-wave Doppler. A significantly lower blood flow was evident in the benign tumours with a markedly increased resistance index (by 80%) established by means of the pulsed-wave Doppler. Continuous-wave (CW) Doppler showed a significantly higher blood flow with almost all malignomas in the entire breast, than was the case with benign changes. Our studies showed, that the enhanced blood flow in and around malignant tumours can be visualised by means of update technology, angiodynography being particularly suitable for demonstrating the flow by the B-mode. Quantification, however, is, at present, only possible by employing the duplex method with pulsed-wave Doppler. CW Doppler is suitable only for blood flow diagnosis of the entire organ, but it requires great precision of working method and is time consuming; tumour blood flow cannot be visualised on-target by this method.

Blood Flow Velocity↗
PubMed1992

[Palliative laser therapy in gynecologic oncology].

Local recurrences of carcinomas of the breast and genitals are a severe psychic and physical strain on the patients. Continuous confrontation with an often visible and generally painful tumour manifestation is an indication for palliative treatment, if other oncological therapies can no longer be employed. In these cases, the possibility of laser use represents a new therapeutic approach. In a pilot study at the University of Heidelberg, Department of Obstetrics and Gynaecology, a palliative laser therapy was performed on 45 patients with locally recurrent carcinomas of the breast (n = 29) and genitals (n = 16). Carbon dioxide and Nd:YAG lasers were utilized for tumour resection, vaporisation and coagulation. This new concept, the combined application of both wavelengths has been proved to be most efficient.

Adult↗
PubMed1992

[Diagnosis of tubal function using intraluminal ultrasound--initial results].

The extremely small ultrasound transducers of the intraluminal ultrasound instruments, introduced via catheters, enable diagnosis to be made inside hollow organs. In order to test the possible uses and indications for this new method in gynaecology, we conducted preliminary examinations in the diagnosis of the uterus and tubes. We employed an intraluminal instrument supplied by Dornier. The intraluminal transducers of this instrument have a diameter of 3.5 and 5 F. Following in-vitro examinations, hysteroscopy and laparoscopy/laparotomy were performed in 15 patients during which the transducer was pushed up via the cervix uteri to the tubes with full vision. This was successful in all 15 patients; in 9 cases the transducer could be pushed as far as the distal end. The tubal walls were examined in detail by this method and for the first time it became possible to achieve functional diagnosis of the motility of the tubes. Strictures can be visualised. The endometrium of the uterus, however, cannot as yet be diagnosed exactly by the present-day state of examination technique. If image quality can be further improved, this method will be the first to enable a functional diagnosis of the tubes and the uterus.

Endometrium↗
PubMed1992

Human interferon regulatory factor 1: intron-exon organization.

Interferon (IFN) regulatory factor 1 (IRF-1) is a transcriptional regulatory protein that mediates the transcriptional activation of the IFN-alpha and IFN-beta genes by viruses and IFNs. To characterize the mechanisms that govern the level of IRF-1 in cells, we isolated the IRF-1 gene and characterized the structure of its intronic and exonic domains and of its regulatory promoter region. A human placental genomic library was screened with an IRF-1 cDNA probe, and two clones that contained the IRF-1 gene and its 5' regulatory region were obtained. We used these clones to determine the complete nucleotide sequence for the IRF-1 gene, finding that the IRF-1 gene spanned 7.72 kb of DNA and included 10 exons and 9 introns. When the deduced amino acid sequences were compared among different species, the most conserved exons were exons 2, 3, and 4, in which the putative DNA binding domain for the IRF-1 protein is located.

Amino Acid Sequence↗
PubMed1992

Purification, characterization and inhibition by fluoride of enolase from Streptococcus mutans DSM 320523.

Enolase from Streptococcus mutans has been purified to homogeneity by a three-step procedure. As shown by analytical ultracentrifugation and polyacrylamide gel electrophoresis under denaturing conditions, the purified enzyme is an octamer with molecular weight Mr = 360 kDa, composed of eight identical subunits with Mr = 45 kDa. The kinetic parameters of S. mutans enolase in the presence of 1 mM Mg2+ are Aspec = 130 IU x mg-1 and KM = 0.44 mM as determined by steady-state experiments in the D-glycerate 2-phosphate to enolpyruvate phosphate reaction. Enzymatic activity is inhibited noncompetitively by fluoride in the range between 0 and 10 mM NaF yielding Ki = Kii = 1.39 mM, but inhibition characteristics become competitive when tested above 10 mM. In the presence of only small amounts of phosphate (0.5 mM) the inhibitory effect of fluoride is enhanced dramatically yielding Ki = 0.26 mM. Inhibition by NaPO3F is competitive with Ki = 0.9 mM, indicating that free fluoride ions in combination with phosphate are more effective in inhibiting S. mutans enolase. It can be concluded that inhibition of enolase by fluoride in combination with phosphate can influence glycolysis in S. mutans and so reduce acid production or even growth rate, thereby leading to potential anticariogenic effects.

Buffers↗