Biomedical subjects

S Dunn

Publications and source records attributed to S Dunn.

At least 55 records · Page 3Linked to original sources

PubMed1997

Pharmacokinetics of an oral solution of the microemulsion formulation of cyclosporine in maintenance pediatric liver transplant recipients.

BACKGROUND: A comparison of the oral bioavailability of cyclosporine from the original formulation (CsA) and from the new formulation, cyclosporine for microemulsion (CsA-ME), was made in pediatric maintenance liver transplant patients within two age groups (group 1, ages 1-5 years; group 2, ages 6-17 years) in an open-label, multicenter, randomized crossover trial. All patients were at least 6 months past transplantation and were receiving CsA maintenance therapy. METHODS: In study period 1 (days 1 through 14), patients were administered either CsA or CsA-ME at the same b.i.d. dosage as their maintenance therapy. Upon entry into period 2 (days 15 through 28), patients were converted to the alternate formulation at a 1:1 mg dose ratio. On day 29, all patients returned to the CsA treatment administered at study entry, with follow-up on day 35. Dosage adjustments were not allowed with either CsA or CsA-ME. Twelve-hour pharmacokinetic profiling was performed at the end of periods 1 and 2. RESULTS: Both the mean area under the concentration-versus-time curve and the mean maximum blood concentration of cyclosporine-both normalized for dose-were significantly increased: by 66% and 109%, respectively, in patients receiving CsA-ME compared with those receiving CsA in group 1 and by 39% and 75%, respectively, in group 2. During this study, liver function remained stable, and serum creatinine and blood pressure did not differ significantly between treatment groups. CONCLUSIONS: This study shows increased bioavailability in all patients converted to CsA-ME, with the greatest increase seen in patients with the lowest initial cyclosporine bioavailability. The tolerability was similar between the two formulations during this study.

Absorption↗

PubMed1997

Long circulating biodegradable poly(phosphazene) nanoparticles surface modified with poly(phosphazene)-poly(ethylene oxide) copolymer.

The biodistribution of biodegradable poly(organo phosphazene) nanoparticles surface modified by adsorption of a novel poly(organo phosphazene)-poly(ethylene oxide) copolymer with a 5000 M(W) PEO chain (PF-PEO[5000]), following intravenous administration in rats and rabbits, is described. The data are compared to the biodistribution of poly(organo phosphazene) and poly(lactide-co-glycolide) nanoparticles coated with a tetrafunctional copolymer of poly(ethylene oxide)-poly(propylene oxide) ethylenediamine, commercially available as Poloxamine 908. This copolymer has a PEO chain of the same size as the poly(organo phosphazene)-PEO derivative used. The results in the rat model reveal that poly(organo phosphazene) nanoparticles with a Poloxamine 908 coating were mainly captured by the liver, although a retardation in clearance from the systemic circulation was seen. In contrast, the poly(organo phosphazene) nanoparticles coated with PF-PEO(5000) showed a prolonged blood circulating profile, with only a small amount of the nanoparticles sequestered by the liver. This indicates the importance of the nature of both the anchoring group and the particle surface on the biological performances of the system. Study of the biodistribution of the PF-PEO(5000)-coated poly(organo phosphazene) nanoparticles in the rabbit model also indicated a prolonged systemic circulation lifetime and reduced liver uptake, whereby a significant amount of the administered nanoparticles was targeted to the bone marrow.

Animals↗

PubMed1997

Meeting patient expectations in the cancer consultation.

BACKGROUND: Low scores on satisfaction measures may be anticipated when patients' expectations of the doctor are unmet during the cancer consultation. We correlated discrepancies between patient expectations of their ideal doctor and their perceptions of their actual doctor with scores on a validated satisfaction scale to determine whether patients whose expectations were unmet were less satisfied. PATIENTS AND METHODS: The expectations questionnaire used a forced choice method designed to elicit patient preferences for either emotional or informational support from the physician. One hundred and five new patients with heterogeneous cancers, of five medical oncologists at a major teaching hospital were sampled. The patients were mostly female (55%) middle aged (mean age 54.3) and newly diagnosed with cancer (56% within two months prior to consultation). RESULTS: Patients did not demonstrate a clear preference for an emotionally or informationally supportive approach. Seventy percent of patients did not want emotionally negative physicians but most (88.4%) would tolerate negative information. The mean number of exact matches between patients expectations of the ideal and their perceptions of their actual doctor was 3.7 (from a total of six). 5.9% of patients received exactly the doctor they wanted. No significant differences in satisfaction were found between patients whose expectations were met and those whose expectations were not met. CONCLUSIONS: Patient satisfaction with the consultation was independent of patient expectation for informational or emotional support.

Adult↗

PubMed1997

Randomized comparison of ganciclovir plus intravenous immune globulin (IVIG) with IVIG alone for prevention of primary cytomegalovirus disease in children receiving liver transplants.

A randomized placebo-controlled trial was conducted to determine the benefit of ganciclovir (5 mg/[kg x d]) for 30 days in addition to intravenous immune globulin (IVIG) for 16 weeks for prevention of primary cytomegalovirus (CMV) disease in children receiving liver transplants. Patients were monitored for 6 months after transplantation. The two groups of patients (recipients of 29 ganciclovir plus IVIG and 27 recipients of IVIG alone) were similar in terms of age, sex, and underlying disease. The incidence of CMV disease among the ganciclovir plus IVIG recipients and the IVIG alone recipients was 17% and 26%, respectively, and the time to disease in these recipients was 46 days and 32 days, respectively. There was no difference between groups in terms of survival; episodes of rejection, bacteremia, or fungemia; use of immunosuppressive agents; and incidence of leukopenia or thrombocytopenia. These results suggest that a 4-week course of ganciclovir with IVIG is not more effective than IVIG alone for prevention of primary CMV disease. Since short-term prophylaxis with ganciclovir may delay the onset of CMV disease, further studies with a longer course of ganciclovir prophylaxis are warranted.

Adolescent↗

PubMed1997

Experiences of physical and sexual abuse in Australian general practice attenders and an eating disordered population.

OBJECTIVE: To determine the reported rates of child physical and sexual abuse experienced by hospitalised eating disordered patients compared to a control group of women attending general practitioners. METHOD: A retrospective survey using the self-report Finkelhor Sexual Life Events Inventory and clinical reports. RESULTS: Nearly one-half of eating disordered patients reported a history of child sexual abuse and one-quarter reported child physical abuse. These rates were significantly higher than those reported by the control group. CONCLUSIONS: Direct questioning regarding trauma histories is warranted when assessing patients with eating disorders and attention to such issues should be incorporated into the total management plan.

Adolescent↗

PubMed1997

Prolonged inhibition of cholesterol synthesis explains the efficacy of atorvastatin.

HMG-CoA reductase inhibitors or statins are effective in both the primary and secondary prevention of coronary heart disease, the extent of benefit being proportional to the reduction in low density lipoprotein (LDL) cholesterol achieved. Atorvastatin, a newly licensed compound, reportedly lowers LDL with greater efficacy than other statins. The mechanism of this action was, therefore, explored in twenty patients with refractory familial hypercholesterolemia who received in a single-blind sequence simvastatin 40 mg/day, placebo and atorvastatin 10 mg/day each for 4 weeks. At the end of the placebo period the effects of single 40-mg doses of simvastatin and atorvastatin on plasma levels and urinary excretion of mevalonic acid, indices of HMG-CoA reductase activity, were compared. Administration of atorvastatin 10 mg daily for 1 month lowered LDL cholesterol by 32.5%, compared with placebo (P = 0.0001), which was 4.5% less than the decrease after simvastatin 40 mg daily (P = 0.33). The area under the plasma curve and urinary mevalonic acid/ creatinine ratio were both significantly less during the 24 h after a single dose of atorvastatin 40 mg than after a single dose of simvastatin 40 mg (P < 0.01). These findings suggest that the greater efficacy of atorvastatin compared with simvastatin is due to more prolonged inhibition of HMG-CoA reductase, presumably reflecting longer residence of atorvastatin or its active metabolites in the liver.

Anticholesteremic Agents↗

PubMed1997

Histological, clinical, and digital subtraction radiographic evaluation of repair of periodontal defects resulting from mechanical perforation of the chamber floor using ePTFE membranes.

The aim of this study was to test the hypothesis that a biocompatible membrane, when placed between the gingiva and cortical bone in teeth with periodontal defects that occurred following mechanical endodontic perforation, would facilitate greater regeneration than in control sites not treated with guided tissue regeneration. One beagle dog with a healthy periodontium was used in the study. The maxillary right first and second molars and the mandibular left first and second molars acted as the experimental group in which furcation perforations were treated by guided tissue regeneration. The maxillary left and mandibular right first and second molars served as the controls in which furcation perforation lesions were only treated by open flap debridement. Clinical, histological, and standardized radiographic evaluation showed significant differences between the test and control groups. In addition, digital subtraction radiography revealed a gain in alveolar bone height and increased density at all experimental sites, and a loss at all control sites. Histological evaluation showed extensive regeneration of both alveolar bone and connective tissue at experimental sites, but none at control sites. The results of this study suggest that the use of guided tissue regeneration in furcation lesions produced by endodontic perforations will result in significant new bone and connective tissue attachment.

Animals↗

PubMed1996

Related donor liver transplant for veno-occlusive disease following T-depleted unrelated donor bone marrow transplantation.

Veno-occlusive disease (VOD) is the third leading cause of mortality after bone marrow transplant. Management consists of supportive care, with restricted fluids and diuretics. Most patients will recover, but approximately 25% may develop severe life threatening VOD with subsequent respiratory compromise and multiorgan failure. Orthotopic liver transplant has been attempted for a few patients with intractable VOD, but this approach is limited by availability of a cadaveric organ. We report a child who underwent a T-depleted unrelated donor bone marrow transplant for severe aplastic anemia as a manifestation of Schwachman-Diamond syndrome who developed severe VOD. She had evidence of engraftment when liver transplant was considered, and had no evidence of major organ dysfunction. The left lateral segment of her mother's liver was transplanted at day +33 following bone marrow transplantation. The child remains well ten months post-BMT and nine months after liver transplant. A related donor liver transplant may be a justifiable approach in a patient with severe VOD post-BMT.

Bone Marrow Cells↗

PubMed1996

Pharmacokinetics of cyclosporine after renal transplant in children.

The pharmacokinetics of cyclosporine and the relationship between blood levels and average drug concentration were prospectively evaluated in 18 children 1 month after renal transplantation. All children had normal renal function and no hepatic or gastrointestinal dysfunction. Cyclosporine was administered after an overnight fast, and serial blood samples were drawn over a 24-hour period. Analysis of cyclosporine levels was performed by means of monoclonal radio immunoassay on whole blood. Children were divided into three age groups for comparison: 2-5 years, 5-10 years, and > 10 years. There were no differences between age groups in serum protein, serum lipids, or hemoglobin levels, or in the pharmacokinetic parameters of cyclosporine except as follows: significant differences were noted in cyclosporine dose based on body weight, apparent steady-state volume of distribution, and apparent blood clearance, with the youngest children (2-5) requiring higher doses, a relative greater distribution, and exhibiting more rapid drug clearance than those > 10 years of age. In addition, we observed diurnal variation in trough levels, with morning levels (0 hr) significantly higher than those obtained in the evening (12 hours after administration of cyclosporine). Trough levels demonstrated a fair correlation with area under the concentration-time curve (AUC) and average concentration (Cav), but an abbreviated kinetic profile using cyclosporine levels 1 and 3.5 hours after administration accurately predicted AUC.

Adolescent↗

PubMed1996