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Biomedical subjects

D Adam

Publications and source records attributed to D Adam.

At least 109 records · Page 6Linked to original sources
PubMed1998

Step baroreflex response in awake patients undergoing carotid surgery: time- and frequency-domain analysis.

Step baroreceptor stimulation can provide an insight into the baroreflex control mechanism, yet this has never been done in humans. During carotid surgery under regional anesthesia, a step increase in baroreceptor stimulation occurs at carotid declamping immediately after removal of the intra-arterial atheromatous plaque. In 10 patients, the R-R interval and systolic and diastolic blood pressures (BP) were continuously recorded, and signals obtained within the time window from 10 min before until 10 min after carotid declamping were analyzed. Mean +/- SD time signals, power spectra, and transfer and coherence functions before and after declamping were calculated. Immediately after carotid declamping, both heart rate (HR) and BP declined in an exponential-like manner lasting 10.3 +/- 5.9 min, and their power spectra increased in the entire frequency range. Transfer function magnitude and coherence functions between BP and HR increased predominantly in the midfrequency region (approximately 0.1 Hz), with no change in phase function. Thus, in carotid endarterectomy patients, step increase in baroreceptor gain elicits a prolonged decline in HR and BP. Frequency analyses support the notion that the baroreflex control mechanism generates the midfrequency HR and BP variability, although other frequency regions are also affected.

Aged↗
PubMed1998

Overview of the clinical features of cefixime.

Third-generation cephalosporins in oral formulations have become an increasingly important first-line choice against common bacterial infections. Cefixime is one such agent, which possesses excellent efficacy against a broad spectrum of pathogens, including Haemophilus influenzae, Streptococcus pneumoniae and Moraxella catarrhalis. Clinical success rates are similar to cefaclor, clarithromycin, and other cephalosporins. Importantly, cefixime also possesses excellent activity against beta-lactamase-producing strains. The pharmacodynamic features of the drug include a half-life of 3-4 h and a Cmax of 4.4 microg/ml, well above the MIC90 for susceptible pathogens, permitting once-daily dosing. In this brief overview, the bacteriological and clinical efficacy of cefixime is discussed, as well as its indications.

Bacterial Infections↗
PubMed1998

Costs of F-18-FDG PET: experience with a satellite concept.

AIM: One of the main arguments against the acceptance and introduction of FDG PET as a regular benefit in the statutory Medical Insurance system in Germany are its (alleged) high costs. The aim of the present study has been to determine empirically over a period of twelve months the costs of FDG PET, making use of a satellite concept. METHODS: Documentation on performance and consumption data has been assembled for purposes of cost analysis. After analysis these data provided the basis for an assessment of the costs. In view of the high proportion of fixed overheads and strong fluctuations in consumption values, it was not possible to allocate reliably in an individual FDG PET investigation the various types of costs to individual causes. A monthly cost assessment procedure was therefore adopted. For this purpose data were recorded in the department for Nuclear Medicine, while the statistical assessment of the consumption data and analysis of the costs were undertaken in the Institute of Industrial and Hospital Management. RESULTS: Over the twelve month observation period (November 1995 to October 1996, 177 working days) 433 patients were included in the study: 244 with brain diseases 37 cardiac patients, 130 whole body studies and 22 combined studies (brain and whole body scans). The non volume based costs, maintenance charges and depreciation accounted for the highest proportion of the total costs (48%). The FDG-related costs accounted for 41% of the total costs, while the personnel costs amounted to 11% and the film costs to only 0.45%. The total costs incurred amounted to DM 1,205,050. CONCLUSION: These data represent a first empirical cost analysis for FDG PET based on a satellite concept and form a starting point for a cost/benefit analysis of this procedure.

Brain↗
PubMed1997

Inhibitory effect of heparin on neutrophil phagocytosis and burst production using a new whole-blood cytofluorometric method for determination.

The influence of heparin on Polymorphonuclear (PMN s) leukocytes was investigated using a new whole-blood cytofluorometric method (patent granted for the test with the number P 4334935.8-41) with Candida albicans and Staphylococcus aureus as test microorganisms. After comparing the effect of equal volumes of two widely used heparins we examined the influence of 5 different heparin-concentrations. Using both yeasts and bacteria, we found a significant, dose-depending decrease of the percentage of phagocyting PMN's and of phagocytized microorganisms as well as of the resulting percentage of PMN s producing respiratory burst along the kinetics. Furthermore we could demonstrate that heparin independently of phagocytosis produces a dose-dependent decrease of burst production of PMN's. Our results indicate that the use of heparins as anticoagulant for immunological investigations as well as clinically with patients under immunosuppressive therapy should be critically reconsidered. This applies even more because due to the evaluated dose-dependent decrease of phagocyte function no boundary for the inhibiting effect can be declared.

Adult↗
PubMed1997

[Therapy of infections in patients with acute leukemia].

BACKGROUND: Infections are the major cause for treatment failure in acute leukemias. They mostly present as fever of unknown origin (FUO), a smaller but prognostically unfavorable group are pneumonias. The effective management of infectious complications requires a symptom and response adapted interventional strategy. THERAPEUTICAL APPROACH: In case of FUO standard therapy consists of the two drug combination of aminoglycoside plus acylaminopenicillin or third generation cephalosporine. In case of non-response carbapenems and a glycopeptide should be applied and a systemic antifungal treatment must be initiated. In pneumonia amphotericin B should be added to antibiotics already initially. Potent single agents with a broad spectrum of activity as well as new antifungal drugs provide attractive perspectives for future evaluations. CONCLUSIONS: By a consequent step-wise oscalating interventional treatment strategy infections in patients with acute leukemias can be successfully treated.

Acute Disease↗
PubMed1997

Changes in platelet count, coagulation and fibrinogen associated with elective repair of asymptomatic abdominal aortic aneurysm and aortic reconstruction for occlusive disease.

BACKGROUND: Mortality and morbidity following aortic surgery, particularly repair of ruptured abdominal aortic aneurysm (AAA), is frequently associated with the development of coagulopathy. OBJECTIVES: To examine changes in platelet count (PC), fibrinogen, and coagulation in patients undergoing elective repair of asymptomatic abdominal aortic aneurysm (AAA) and aortic surgery for occlusive disease. DESIGN: Prospective clinical study in a University Department of Vascular Surgery. PATIENTS: Thirty-three patients undergoing elective repair of asymptomatic AAA and 19 patients undergoing aortic surgery for occlusive disease. METHODS: Full blood count (FBC), clotting screen, and fibrinogen measured pre-operatively; 6, 12, 24, 48 h postoperatively; and thereafter as clinically indicated in 23 consecutive patient's undergoing AAA repair (Group 1). Pre- and postoperative PC measured weekly for 4 weeks following operation in a further 10 consecutive patients undergoing AAA repair (Group 2) and perioperative PC measured in 19 consecutive patients undergoing aortic surgery for occlusive disease (Group 3). RESULTS: Group 1: Preoperative haematological parameters were normal. There was no mortality. Postoperatively, 21 (91%) patients developed thrombocytopenia (PC < 150 x 10(9)/l). The postoperative fall in PC (median 90, range 12-160 x 10(9)/l) was significantly related to the duration of aortic cross-clamp (median 46, range 20-127 min, r2 = 0.33, p < 0.01). At 10 days all patients had developed thrombocytosis (PC > 350 x 10(9)/l) Postoperatively, by 48 h, 17 (74%) patients had developed hyperfibrinogenaemia. One patient suffered a myocardial infarction associated with a PC of 105 x 10(9)/l and a fibrinogen of 7.2 g/l. GROUP 2: In a further 10 patients undergoing AAA repair postoperative thrombocytosis was found to persist for several weeks in five of nine survivors. GROUP 3: Patients undergoing aortic surgery for occlusive disease had significantly higher preoperative PC than AAA patients (median 292, range 179-251 x 10(9)/l vs. median 204, range 140-293 x 10(9)/l, p < 0.01). CONCLUSIONS: Patients undergoing elective repair of AAA demonstrate similar, albeit less dramatic, changes in platelet count to those we have previously reported in patients undergoing repair of ruptured AAA. Aortic clamping leads to platelet sequestration and thrombocytopenia in the early postoperative period. Later, patients develop hyperfibrinogenaemia and thrombocytosis which may persist for several weeks. Similar changes are seen in patients undergoing aortic surgery for occlusive disease. These changes may represent a hypercoagulable state that predisposes these patients to thrombotic complications.

Aged↗
PubMed1996

FAN, a novel WD-repeat protein, couples the p55 TNF-receptor to neutral sphingomyelinase.

The initiation of intracellular signaling events through the 55 kDa tumor necrosis factor-receptor (TNF-R55) appears to depend on protein intermediates that interact with specific cytoplasmic domains of TNF-R55. By combined use of the yeast interaction trap system and a peptide scanning library, the novel WD-repeat protein FAN has been identified, which specifically binds to a cytoplasmic nine amino acid binding motif of TNF-R55. This region has been previously recognized as a distinct functional domain that is both required and sufficient for the activation of neutral sphingomyelinase (N-SMase). Overexpression of full-length FAN enhanced N-SMase activity in TNF-treated cells, while truncated mutants of FAN produced dominant negative effects. The data suggest that FAN regulates ceramide production by N-SMase, which is a crucial step in TNF signaling.

Amino Acid Sequence↗
PubMed1996

Function of the p55 tumor necrosis factor receptor "death domain" mediated by phosphatidylcholine-specific phospholipase C.

Tumor necrosis factor (TNF) is a pleiotropic mediator of inflammation that has been implicated in the pathogenesis of devastating clinical syndromes including septic shock. We have investigated the role of a TNF-responsive phosphatidylcholine-specific phospholipase C (PC-PLC) for the cytotoxic and proinflammatory activity of TNF. We show here that the cytotoxicity signaled for by the so-called "death domain" of the p55 TNF receptor is associated with the activation of PC-PLC. The xanthogenate tricyclodecan-9-yl (D609), a specific and selective inhibitor of PC-PLC, blocked the cytotoxic action of TNF on L929 and Wehi164 cells. In vivo, D609 prevented both adhesion molecule expression in the pulmonary vasculature and the accompanying leukocyte infiltration in TNF-treated mice. More strikingly, D609 protects BALB/c mice from lethal shock induced either by TNF, lipopolysaccharide, or staphylococcal enterotoxin B. Together these findings imply PC-PLC as an important mediator of the pathogenic action of TNF, suggesting that PC-PLC may serve as a novel target for anti-inflammatory TNF antagonists.

Animals↗
PubMed1996

A novel cytoplasmic domain of the p55 tumor necrosis factor receptor initiates the neutral sphingomyelinase pathway.

The human p55 tumor necrosis factor (TNF) receptor (TR55) initiates at least two independent signaling cascades. The acidic sphingomyelinase (A-SMase) pathway involves a phosphatidylcholine-specific phospholipase C, an endosomal A-SMase, and controls expression of multiple TNF-responsive genes through induction of transcription factors such as NF-kappaB. The neutral sphingomyelinase (N-SMase) pathway comprises a membrane-bound N-SMase, proline-directed protein kinases, as well as phospholipase A2 and appears critical for the inflammatory responses induced by TNF. While the domain of TR55 that induces A-SMase is probably identical to the death domain, the exact location and extent of a putative N-SMase activation domain are still unknown. Structure-function analysis of TR55 deletion mutants revealed a novel region of 11 amino acids at position 309-319 that is both necessary and sufficient for activation of N-SMase. The N-SMase activation domain is distinct from the death domain and incapable of induction of A-SMase, NF-kappaB, and cytotoxicity. Taken together, our results suggest that a functionally independent region of TR55 is responsible for selectively initiating the N-SMase pathway that couples to an important inflammatory signaling cascade.

Animals↗
PubMed1996

Five days of erythromycin estolate versus ten days of penicillin V in the treatment of group A streptococcal tonsillopharyngitis in children. Pharyngitis Study Group.

In a randomized, prospective, multicenter trial, 227 children ranging in age from 3 to 17 years who had tonsillopharyngitis and a throat culture positive for group A beta-hemolytic streptococci (GABHS) were treated with erythromycin estolate (40 mg/kg/d in two divided doses for five days) or penicillin V (30 mg/kg/d in three divided doses for ten days). Clinical signs and symptoms of tonsillopharyngitis were recorded, and throat cultures were obtained before treatment as well as one to three days and six weeks after treatment. Clinical success (cure and improvement) was observed on days 6 to 8 in 100 of 102 (98%) assessable children treated with erythromycin estolate and on days 11 to 13 in 97 of 99 (98%) assessable children treated with penicillin V. Of all patients showing clinical success, 11 were rated as improved, all of whom were treated with erythromycin estolate. There was a trend towards increased use of analgesic treatment in the erythromycin estolate group (41% vs 33%). On completion of treatment, the rate of eradication of GABHS was 83.3% in the erythromycin estolate group compared with 87.9% in the penicillin V group. The difference is not significant but does not take into account patients excluded because of erythromycin resistance (3.7%). Clinical recurrence was observed in 11 (10.8%) patients treated with erythromycin estolate and in 6 (6.1%) patients treated with penicillin V (non-significant difference). Compliance in the erythromycin estolate group was statistically superior to that in the penicillin V group. The incidence and nature of adverse events were similar in both treatment groups.

Administration, Oral↗
PubMed1995

Cross-linking of the p55 tumor necrosis factor receptor cytoplasmic domain by a dimeric ligand induces nuclear factor-kappa B and mediates cell death.

We have fused the cytoplasmic domain of the p55 tumor necrosis factor (TNF) receptor to the extracellular and transmembrane domain of the mouse platelet-derived growth factor (PDGF) receptor. Mouse mammary gland epithelial (NMuMG) cells were stably transfected with the PDGFR-TR55 chimeric receptor. These cells lack endogenous PDGF receptor expression and do not respond to PDGF. In the PDGFR-TR55 transfectants, PDGF elicited a cytotoxic response, which is indistinguishable from that induced by the wild type p55 TNF receptor. In addition, PDGF-induced activation of the PDGFR-TR55 chimeric receptor resulted in nuclear translocation of NF-kappa B. The data presented suggest that cross-linking of the p55 TNF receptor cytoplasmic domain by a dimeric ligand such as PDGF is sufficient to generate cellular responses that do not differ from those observed with the trimeric ligand TNF.

Animals↗
PubMed1995

Tumor necrosis factor (TNF)-alpha activates c-raf-1 kinase via the p55 TNF receptor engaging neutral sphingomyelinase.

TNF-alpha mediates proliferation, functional activation and apoptotic death of cells depending upon its concentration and target cell type. The signaling pathways used by TNF-alpha to mount these responses are, at present, not completely understood. We report here that TNF-alpha promotes dose- and time-dependent phosphorylation and activation of the c-raf-1 kinase engaging the type I p55 TNF receptor (TNF-R). c-raf-kinase activation was duplicated by an agonistic monoclonal antibody directed against the p55 TNF-R. Moreover, ectopic expression of the human p55 TNF-R in murine pre-B 70Z/3 cells was sufficient to confer c-raf-1-kinase activation by human TNF-alpha. By inhibiting intracellular activation of acidic sphingomyelinase (SMase) and by using deleted forms of the type I TNF-R it was shown that the neutral, but not the acidic SMase, participated in TNF-alpha-mediated phosphorylation and activation of the c-raf kinase. TNF-alpha-induced transcriptional activation of a heterologous promoter construct harboring the AP-1 binding site was also mediated by the type I p55 TNF-R. In this case the initiation of transcription required the same cytoplasmic domain as that responsible for activation of c-raf-1 kinase and was liberated in the presence of a dominant negative mutant of c-raf-1.

Animals↗
PubMed1995

A model of Ca2+ release from the sarcoplasmic reticulum.

Various functions in the myocyte depend on Ca2+ transport, yet the control of these processes is still obscure. In order to better understand the intracellular Ca2+ processes, a model of Ca2+ release from the cardiac sarcoplasmic reticulum (SR) is suggested, in which the release of Ca2+ from the SR is mainly regulated by the kinetics of Ca2+ channels within the SR membrane. These kinetics are controlled by changes in the concentration of free Ca2+ near the openings of Ca2+ channels, and are affected by Ca2+ competitors, e.g., ryanodine. The control mechanism is based on a combination of positive and negative control loops, associated with two respective types of Ca2+ binding sites located on the SR membrane: 1) activating sites with low affinity to Ca2+ and high binding rate, and 2) inactivating sites with high affinity but low binding rate. The model also assumes that the activation of the Ca2+ channels depends on the preceding stimulation pattern (short term memory), an additional activation mechanism which is Ca2+ independent. This report describes the cytoplasmatic Ca2+ concentration in response to Ca2+ release from the SR, including the dependence on the beat intervals, either in the steady state or during response to premature and delayed beats. The analysis of ryanodine intervention supports a control mechanism based on two feedback loops, and available interval-dependent data favors inclusion of the short-term memory mechanism in the proposed model.

Animals↗