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Biomedical subjects

D Adam

Publications and source records attributed to D Adam.

At least 73 records · Page 4Linked to original sources
PubMed2001

Comparative efficacy of clarithromycin modified-release and clarithromycin immediate-release formulations in the treatment of lower respiratory tract infection.

BACKGROUND: A modified-release (MR) formulation of clarithromycin, distinct from the extended-release formulation, has recently been developed and has efficacy and tolerability similar to standard immediate-release (IR) clarithromycin, with the advantage of once-daily dosing. OBJECTIVE: The purpose of this study was to compare the efficacy (as measured by relief of clinical symptoms and eradication of specific pathogens) and tolerability of clarithromycin MR 500 mg administered once daily versus clarithromycin IR 250 mg administered twice daily for 5 days. METHODS: In this randomized, double-blind (with matching placebo), parallel-group. multicenter, controlled trial, patients with lower respiratory tract infection were randomized to 1 of 2 treatment regimens: clarithromycin MR 500 mg once daily plus clarithromycin IR 250 mg placebo twice daily or clarithromycin IR 250 mg BID plus clarithromycin MR 500 mg placebo once daily. RESULTS: Statistically equivalent clinical cure and success rates, overall symptomatic improvement, and bacteriologic responses were achieved with both treatments. In the clarithromycin MR group, the clinical cure rate was 72.5% (87/120), and the clinical success rate (cure plus symptomatic improvement) was 97.5% (117/120). Of the 124 patients treated with clarithromycin IR 250 mg BID, 98 (79.0%) achieved a clinical cure, and 120 (96.8%) achieved clinical success. There were no statistically significant between-group differences in clinical cure or success rates. More than 85% of patients in both study groups experienced improvement in dyspnea, cough, wheezing, chest discomfort, fatigue, and fever, and the visual appearance of sputum: these symptoms resolved completely in the majority of patients. Bacteriologic response (efficacy against specific pathogens), which was assessed as an objective efficacy criterion, was assessable for 40 patients treated with clarithromycin MR and 49 patients treated with clarithromycin IR. Bacteriologic eradication of the pretreatment target pathogen was achieved in 95.0% (38/40) of assessable patients treated with clarithromycin MR 500 mg once daily and 91.8% (45/49) of patients treated with clarithromycin IR 250 mg BID. Treatment-related adverse events were mild to moderate in all cases. Nausea (n = 9), diarrhea (n = 6), abdominal pain (n = 5), and gastric pain (n = 3) were the only study drug-related adverse events reported by > or = 1 patient in each treatment arm. Diarrhea was reported only in the clarithromycin IR group (n = 6) (P = 0.029 vs clarithromycin MR). CONCLUSIONS: Clarithromycin MR 500 mg administered once daily for 5 days is as effective and well tolerated as the IR formulation, with the advantage of once-daily dosing and fewer episodes of diarrhea.

Adolescent↗
PubMed2001

Validation of ultrasonic image boundary recognition in abdominal aortic aneurysm.

An aneurysm of the abdominal aorta (AAA) is characterized by modified wall properties, and a balloon-like area usually filled by a thrombus. A rupture of an aortic aneurysm can be fatal, yet there is no way to accurately predict such an occurrence. The study of the wall and thrombus cross-sectional distension, due to a pressure wave, is important as a way of assessing the degradation of the mechanical properties of the vessel wall and the risk of a rupture. Echo ultrasound transverse cross-sectional imaging is used here to study the thrombus and the aortic wall distension, requiring their segmentation within the image. Polar coordinates are defined, and a search is performed for minimizing a cost function, which includes a description of the boundary (based on a limited series of sine and cosine functions) and information from the image intensity gradients along the radii. The method is based on filtering by a modified Canny-Deriche edge detector and then on minimization of an energy function based on five parts. Since echoes from blood in the lumen and the thrombus produce similar patterns and speckle noise, a modified version for identifying the lumen-thrombus border was developed. The method has been validated by various ways, including parameter sensitivity testing and comparison to the performance of an expert. It is robust enough to track the lumen and total arterial cross-sectional area changes during the cardiac cycle. In 34 patients where sequences of images were acquired, the border between the thrombus and the arterial wall was detected with errors less than 2%, while the lumen-thrombus border was detected with a mean error of 4%. Thus, a noninvasive measurement of the AAA cross-sectional area is presented, which has been validated and found to be accurate.

Algorithms↗
PubMed2001

Management of sepsis and septic shock in infants and children.

Sepsis and septic shock constitute an important cause of morbidity and mortality in critically ill children. Thus, the systemic response to infection and its management remains a major challenge in clinical medicine. Apart from antibiotic administration, the majority of available therapies are limited to supportive strategies, although considerable efforts are being undertaken to devise innovative approaches that modulate host inflammatory responses. In suspected sepsis, 2 or 3 days' empiric antibiotic therapy should begin immediately after cultures have been obtained without awaiting results. Antibiotics should be re-evaluated when the results of the cultures and susceptibility tests are available. The initial antibiotic (combination) is determined by the likely causative agent, susceptibility patterns within a specific institution, CNS penetration, toxicity, and the patient's hepatic and renal function. The likely offending micro-organism in turn depends primarily on the patient's age, coexistence of any premorbid condition leading to impaired immune response, and the presenting signs and symptoms. Close attention to cardiovascular, respiratory, fluid and electrolyte, haematological, renal and metabolic/nutritional support is essential to optimise outcome. Fluid resuscitation is of utmost importance to overcome hypovolaemia on the basis of a diffuse capillary leak. Monitoring and normalisation of the heart rate is essential. In case of nonresponse to fluid resuscitation, inotropic and vasoactive agents are commonly used to increase cardiac output, maintain adequate blood pressure and enhance oxygen delivery to the tissue. Because respiratory distress syndrome is seen in about 40% of critically ill children with septic shock, increased inspired oxygen is essential. To provide optimal relief from respiratory muscle fatigue and facilitate the provision of positive airway pressure, early intubation and mechanical ventilation should be considered. Renal support is essential to avoid prolonged renal shutdown in hypoperfusion states. Haematological support comprises replacement therapy of clotting factors to overcome disseminated intravascular coagulation. Metabolic support may include glucose support, extraction of ammonia from the body and recognition of liver dysfunction. Nutritional support may modify the inflammatory host response, and early enteral feeding can improve outcome in critical illness. To date, glucocorticoid and non-glucocorticoid anti-inflammatory agents have not shown significant benefit in septic patients.

Anti-Bacterial Agents↗
PubMed2000

Stimulation of cellular sphingomyelin import by the chemokine connective tissue-activating peptide III.

The selective import of phospholipids into cells could be mediated by proteins secreted from the cells into the extracellular compartment. We observed that the supernatants obtained from suspensions of thrombin-activated platelets stimulated the exchange of pyrene (py)-labeled sphingomyelin between lipid vesicles in vitro. The proteins with sphingomyelin transfer activity were purified and identified as the chemokine connective tissue-activating peptide III (CTAP-III) and platelet basic protein. Isolated CTAP-III stimulated the exchange of py-sphingomyelin between lipid vesicles but did not affect the translocations of py-labeled phosphatidylcholine and phosphatidylethanolamine. CTAP-III rapidly increased the transfer of py-sphingomyelin from low density lipoproteins into peripheral blood lymphocytes, other immune cells, and fibroblasts. In the presence of heparin, CTAP-III was unable to insert sphingomyelin into the peripheral blood lymphocytes. The activation energy of the py-sphingomyelin transfer suggested that the translocation proceeded entirely in a hydrophobic environment. [(3)H]Sphingomyelin transferred to the cells by CTAP-III was hydrolyzed to [(3)H]ceramide and [(3)H]sphingosine after activation with tumor necrosis factor alpha. The generation of the [(3)H]sphingolipid messengers was catalyzed by acid sphingomyelinase. Our results identify CTAP-III as the first mediator of the selective (endocytosis-independent) cellular import of sphingomyelin allowing the paracrine modulation of the sphingolipid signaling.

Biological Transport↗
PubMed2000

Influence of fluconazole on phagocytosis, oxidative burst and killing activity of human phagocytes. Using a flow cytometric method with whole blood.

OBJECTIVES: The aim of this study was to investigate the influence of fluconazole, an antimycotic on phagocytosis, oxidative burst and killing activity of phagocytes in human whole blood with Candida albicans as a test strain using a flow cytometric method. METHODS: Candida albicans was stained with Calcein AM, a greenfluorescent dye from Bioprobes (Molecular Probes, Inc., P.O. Box 22010, Eugene, OR 97402-0469, USA). To measure phagocytosis and burst activity diluted monoclonal antibody (CD-13-R-PE, Molecular Probes, Inc., P.O. Box 22010, Eugene, OR 97402-0469, USA) attaching at the surface of granulocytes and monocytes was added as well as Dihydroethidium solution (Molecular Probes, Inc., P.O. Box 22010, Eugene, OR 97402-0469, USA) which changes into red fluorescent Ethidium by oxidation when killing activity takes place. With Ethidium-Homodimer-1-solution (Molecular Probes, Inc., P.O. Box 22010, Eugene, OR 97402-0469, USA) killing activity can be observed. Three different tests, one incubating the Candida for 1- 4 hrs in advance, another incubating whole blood for 1 h, and the third incubating neither yeast nor blood, and a combined main test were carried out. Measurement of phagocytosis, burst- and killing activtiy was performed with a flow cytometric method (Coulter Company, type: Epics-Profile II). RESULTS: Three different concentrations of fluconazole (5, 20 and 100 microg/ml) show neither decreasing nor increasing influence on phagocytosis and burst activity, irrespective of whether yeasts or phagocytes had been incubated with fluconazole in advance or not. Also after incubating the drug with phagocytes for 1 h, neither an increase nor a decrease of killing activity was observed. A significant increase was, however, found with increasing incubation time of yeasts and fluconazole. - The minimum concentration of fluconazole, just enough to show a significant increase of the killing rate was 1 microg/ml after 3hrs of incubation. No further significant increase was detected when the concentration exceeded 5 microg/ml. CONCLUSION: 1 h incubation of human phagocytes with fluconazole does not have any significant influence on cellular activities. After advanced incubation of Candida a corresponding increase of the intracellular killing rate in phagocytes occurs, probably due to changes of the cytomorphology of yeasts.

Antifungal Agents↗
PubMed2000

Overexpression of acid ceramidase protects from tumor necrosis factor-induced cell death.

Tumor necrosis factor (TNF) signals cell death and simultaneously induces generation of ceramide. To evaluate the contribution of ceramide to TNF-dependent cell death, we generated clones of the TNF-sensitive cell line L929 that constitutively overexpress human acid ceramidase (AC). Ceramidase, in concert with sphingosine kinase, metabolizes ceramide to sphingosine-1-phosphate (SPP), an inducer of proliferation. In response to TNF, parental L929 cells display a significant increase in intracellular ceramide correlated with an "atypical apoptosis" characterized by membrane blebbing, DNA fragmentation and degradation of poly(ADP-ribose) polymerase despite a lack of caspase activity. These features are strongly reduced or absent in AC-overexpressing cells. Pharmacological suppression of AC with N-oleoylethanolamine restored the accumulation of intracellular ceramide as well as the sensitivity of the transfectants to TNF, implying that an enhanced metabolization of intracellular ceramide by AC shifts the balance between intracellular ceramide and SPP levels towards cell survival. Correspondingly, inhibition of ceramide production by acid sphingomyelinase also increased survival of TNF-treated L929 cells.

Acid Ceramidase↗
PubMed2000

Activation of ERK1/2 and cPLA(2) by the p55 TNF receptor occurs independently of FAN.

The generation of proinflammatory eicosanoids in response to tumor necrosis factor (TNF) involves the activation of cytosolic phospholipase A(2) (cPLA(2)), presumably by phosphorylation through extracellular signal-regulated kinases (ERK). Earlier results had suggested that a pathway involving the p55 TNF receptor (TNF-R55), neutral sphingomyelinase (N-SMase), and c-Raf-1 activates ERK and cPLA(2). We have previously shown that a cytoplasmic region of TNF-R55 distinct from the death domain regulates the activation of N-SMase through binding of the adapter protein FAN. Analysis of embryonal fibroblasts from FAN knockout mice revealed that TNF-induced activation of both ERK and cPLA(2) occurs without involvement of FAN. Furthermore, we provide evidence that the TNF-dependent activation of ERK and cPLA(2) requires the intact death domain of TNF-R55. Finally, we demonstrate that in murine fibroblasts cPLA(2) is phosphorylated in response to TNF solely by ERK, but not by p38 mitogen-activated protein kinase, suggesting a signaling pathway from TNF-R55 via the death domain to ERK and cPLA(2).

Animals↗