Biomedical subjects

D Raible

Publications and source records attributed to D Raible.

10 recordsLinked to original sources

PubMed2004

Population-based pharmacokinetics of the soluble TNFr etanercept: a clinical study in 43 patients with ankylosing spondylitis compared with post hoc data from patients with rheumatoid arthritis.

OBJECTIVE: The purpose of this study was to evaluate the pharmacokinetics of etanercept in patients with ankylosing spondylitis (AS) in a phase 3 study. METHODS: Serum etanercept concentrations were analyzed from samples obtained at weeks 4 and 12 from 43 patients with AS (median age: 45 years; median body weight: 75 kg; white/non-white: 40/3; male/female: 34/9) receiving 25 mg subcutaneously twice weekly for 12 weeks. A population pharmacokinetics analysis using NONMEM was conducted to estimate individual etanercept pharmacokinetic parameters. Initially, appropriate base and covariate population pharmacokinetic models were built based on data from 10 prior clinical studies of etanercept administered subcutaneously or intravenously to healthy subjects (n = 53) and to patients with rheumatoid arthritis (RA) (n = 212). The influence of demographic characteristics on the pharmacokinetics of etanercept was thoroughly evaluated. The stability of the final model was evaluated using both internal (bootstrapping) and external (data splitting) validation approaches. Finally, the selected final population covariate model was used to estimate the Bayesian pharmacokinetic parameters for the patients with AS. RESULTS: The data from the 10 prior clinical studies were optimally fitted to a 2-compartment linear population covariate model. Both age (< 17 years) and body weight (< 60 kg) were found to be important covariates on clearance. Both bootstrapping and data splitting validated the population model. The mean Bayesian-predicted etanercept clearance and steady-state trough concentration were 0.072 l/h and 2,004 ng/ml, respectively. The pharmacokinetic parameters of etanercept in the patients with AS were similar to those observed in the patients with RA. CONCLUSIONS: The pharmacokinetics of etanercept in patients with AS were similar to those in patients with RA. The AS disease state does not appear to alter the disposition of etanercept.

Adult↗

PubMed2001

Idiopathic pneumonia syndrome following myeloablative chemotherapy and autologous transplantation.

OBJECTIVE: To report the outcome as well as the clinical, radiographic, and pathologic features of idiopathic pneumonia syndrome (IPS) following autologous peripheral blood stem cell transplantation (aPBSCT). CLINICAL FINDINGS: A total of 271 patients with a variety of underlying malignancies received busulfan-containing myeloablative chemotherapy prior to aPBSCT; none of these patients received total body irradiation. Ten individuals developed IPS, with a median time of onset of 102 days after stem cell infusion. The major clinical and radiographic findings included an acute or subacute onset of dyspnea, cough, hypoxemia, and bilateral or unilateral infiltrates with or without pleural effusion. Pathologic findings consisted mainly of diffuse interstitial pneumonitis, organizing alveolitis, and cellular atypia. Nine patients diagnosed with IPS were treated with high doses of glucocorticoids parenterally. Despite heroic measures, eight patients died of IPS. The two remaining individuals recovered without experiencing significant long-term pulmonary sequelae. DISCUSSION: Chronic low-dose busulfan therapy results in lung injury in 4-6% of patients after several years of treatment and once the cumulative dosage begins to approach 3g. High-dose, short-course busulfan (16 mg/kg)-containing conditioning chemotherapy prior to aPBSCT can also be complicated by IPS. IPS differs from lung damage due to chronic busulfan therapy by its earlier onset, an acute or subacute rather than indolent presentation, characteristic clinical and radiographic features, and lack of multinucleated giant cells on pathologic review. The pathophysiology of IPS secondary to high-dose busulfan-containing myeloablative regimens is not known, but cell-mediated immune reactions and release of cytokines may contribute to the lung injury. Mortality is high (80%) despite the use of heroic measures, including mechanical ventilation. Some patients, however, can respond to high doses of parenteral corticosteroid therapy. CONCLUSIONS: IPS following high-dose, short-course busulfan-containing regimens exhibits unique clinical, radiographic, and pathologic features that differ from lung damage characteristic of chronic, low-dose busulfan therapy. Mortality from this complication is 80%, but some patients survive without long-term pulmonary sequelae following early treatment with glucocorticoids.

Adolescent↗

PubMed1995

Inhibition of lipid mediator biosynthesis in human inflammatory cells by BIRM 270.

BIRM 270 was developed as a potent and enantioselective inhibitor of LTB4 biosynthesis by human neutrophils, and was also found to inhibit LTC4 production by human eosinophils and lung mast cells. BIRM 270 inhibited LTB4 synthesis in neutrophils by preventing arachidonate release from membrane phospholipids, and over the same concentration range, inhibited PAF biosynthesis. BIRM 270 did not directly inhibit acylhydrolases which have been implicated in eicosanoid and PAF biosynthesis, suggesting an indirect mode of action.

Arachidonic Acid↗

PubMed1993

Collapsin: a protein in brain that induces the collapse and paralysis of neuronal growth cones.

Repulsive guidance cues can steer neuronal growth cones during development and prevent mature axons from regenerating. We have identified a 100 kd glycoprotein in the chick brain that is a good candidate for a repulsive cue. Since it induces the collapse and paralysis of neuronal growth cones in vitro, we have named it collapsin. It is effective at concentrations of approximately 10 pM. The C-terminal half of collapsin contains a single immunoglobulin-like domain and an additional highly basic region. The N-terminal half of collapsin shares significant homology with fasciclin IV, a growth cone guidance protein in grasshopper. Recombinant collapsin causes sensory ganglion growth cones to collapse but not retinal ganglion cell growth cones. We propose that collapsin could serve as a ligand that guides specific growth cones by a motility-inhibiting mechanism.

Amino Acid Sequence↗

PubMed1981

No-needle dialysis (NND): experience with the new carbon transcutaneous hemodialysis (HD) access device (CTAD).

A new carbon transcutaneous access device (CTAD) for hemodialysis id described the precludes the need for needle puncture. The device consists of a vitreous carbon access port attached to a PTFE graft. A disposable connector provides for movement of blood from the device into and out of the dialyzer. Twenty-one of the devices have been implanted in 18 patients. Overall 9 month patency rate is 64.3%, comparing favorably with conventional PTFE grafts. The incidence of infection (1 per .05 patient months) and thrombosis (28.6% at 9 months) similarly compare favorably with other forms of vascular access. The CTAD provides a unique opportunity by permitting hemodialysis without the pain or risk of needle punctures.

Arteriovenous Shunt, Surgical↗

PubMed1980