PubMed Health⌕ Search

Biomedical subjects

R Bassett

Publications and source records attributed to R Bassett.

17 recordsLinked to original sources
PubMed2006

Comparative assessment of the consistency and quality of a highly purified FSH extracted from human urine (urofollitropin) and a recombinant human FSH (follitropin alpha).

The revolutionary development of biotechnology-derived therapeutic proteins has provided the expected improvements in quality, purity and consistency, as demonstrated in recombinant human FSH (rhFSH). However, the development of urine-derived gonadotrophins has not always shown comparable improvements. More recently, highly purified urine-derived FSH (uFSH-HP) products have become widely available. The relative purity, level of urine-derived contaminants, and consistency of one such highly purified human uFSH (uhFSH) (urofollitropin) has been assessed and directly compared with rhFSH (follitropin alpha). It has been demonstrated that the highly purified urofollitropin contains variable levels of urine-derived contaminant proteins and demonstrates a variable level of FSH purity, FSH isoforms, and delivered dose. These variable factors may contribute to the control of ovarian stimulation. The relative purity, variable consistency and the presence of contaminants indicates that the urofollitropin is, at best, a partially purified uFSH that is not able to meet the quality attributes of follitropin alpha (rhFSH).

Blotting, Western↗
PubMed2005

Comparative analytical characterization of two commercial human follicle-stimulating hormones extracted from human urine.

OBJECTIVE: Pharmaceutical preparations of human menopausal gonadotrophin (hMG), urine-derived follicle-stimulating hormone (u-FSH) and highly purified u-FSH (u-FSH-HP) have been available since the early 1960s and the mid 1980s and 1990s, respectively. Another commercial preparation of u-FSH-HP, Folyrmon P, was launched in Japan in 1999. The aim of this study is to assess the purity of Folyrmon P and to compare it with Fertinorm-P, another commercial preparation of u-FSH-HP that has been available since 1993. METHODS: Folyrmon P and Fertinorm-P were assessed for total protein content, biological activity, immunological activity, specific activity, purity and levels of protein contamination. RESULTS: Folyrmon P, which is extracted from the urine of post-menopausal women, has a specific activity of between 4000 and 5000 IU/mg, while Fertinorm-P, which is also manufactured from the urine of post-menopausal women, has a specific activity of at least 10,000 IU/mg. It has been well documented that commercially available hMG and u-FSH preparations can contain a number of urine-derived protein contaminants. This also proves to be the case for Folyrmon P, in which contaminant proteins other than FSH were shown to be present. It was also demonstrated that both preparations, Folyrmon P and Fertinorm-P, contained high levels of oxidized FSH. CONCLUSIONS: The low specific activity and high level of contaminants in Folyrmon P indicate that this u-FSH is not highly purified. Overall, Fertinorm-P, with higher specific activity and lower levels of contaminant proteins, appears to be of higher quality compared with Folyrmon P.

Female↗
PubMed2005

Comparative characterisation of a commercial human chorionic gonadotrophin extracted from human urine with a commercial recombinant human chorionic gonadotrophin.

BACKGROUND: A commercial preparation of recombinant human chorionic gonadotrophin (r-hCG, Ovitrelle) was launched in 2001. Generally, hCG is available in two formats: human chorionic gonadotrophin (u-hCG), derived from the urine of pregnant females, and r-hCG produced by DNA based biotechnology. METHOD: The analytical characteristics of a highly purified u-hCG (Gonasi HP) were assessed and compared, for the first time, with the recombinant derived r-hCG (Ovitrelle). Gonasi HP is produced by extracting and purifying hCG from urine to obtain a specific bioactivity of 5000 IU/mg protein. Ovitrelle is produced via a recombinant derived mammalian cell line and purified to obtain a specific activity of 26 000 IU/mg. RESULTS AND CONCLUSION: It has been documented that commercially available u-hCG preparations can contain a number of urine derived protein contaminants as well as hCG related metabolites. This is also the case for Gonasi HP, where hCG related molecules and other proteins were found to be present, including epidermal growth factor (EGF) and eosinophil derived neurotoxin (EDN). It was also demonstrated that this preparation contained high levels of oxidised hCG. r-hCG was confirmed to be essentially intact hCG, free from contaminant proteins and with very low levels of oxidised hCG.

Chorionic Gonadotropin↗
PubMed2004

Efficacy of cyclosporin in the treatment of atopic dermatitis in dogs--combined results from two veterinary dermatology referral centres.

OBJECTIVE: To evaluate the efficacy of cyclosporin in controlling the clinical signs associated with atopic dermatitis in dogs under Australian field conditions. DESIGN: A multicentre prospective clinical investigation of the use of cyclosporin in 41 dogs with atopic dermatitis. PROCEDURE: Dogs were treated with cyclosporin (5 mg/kg orally once daily with food) for 6 weeks. Four clinical parameters of severity of atopic dermatitis were measured on Day 0 and on Day 42 using a 0 to 4 scoring system. Individual variables were then combined to form a Global Score. Both client and clinician observed pruritus scores were combined to form a Pruritus Score. Pre- and post-treatment scores were statistically analysed. The difference in results between the two investigators was also recorded and analysed. RESULTS: All dogs showed a marked reduction in pruritus and erythema during the 6-week treatment period. All dogs showed a significant (P < 0.001) improvement in clinical lesion scores and Global Score (P < 0.001). The mean percentage improvement in Global Score from Day 0 to Day 42 was 83.9%. The mean percentage improvement in Pruritus Score from Day 0 to Day 42 was 83%. The medication was well tolerated. Side effects such as vomiting, diarrhoea and soft stools were observed in four dogs. Another four dogs developed bacterial pyoderma during the trial period. There was no significant difference in results between the two centres. CONCLUSION: Cyclosporin was well tolerated and efficacious in the symptomatic treatment of atopic dermatitis in dogs attending two veterinary dermatology referral centres in Australia, under Australian field conditions, when administered at 5 mg/kg/day for 6 weeks.

Administration, Oral↗
PubMed2001

Prevalence and predictive value of intermittent viremia with combination hiv therapy.

CONTEXT: In HIV-infected patients having virologic suppression (plasma HIV RNA <50 copies/mL) with antiretroviral therapy, intermittent episodes of low-level viremia have been correlated with slower decay rates of latently infected cells and increased levels of viral evolution, but the clinical significance of these episodes is unknown. OBJECTIVE: To determine if HIV-infected patients with intermittent viremia have a higher risk of virologic failure (confirmed HIV RNA >200 copies/mL). DESIGN AND SETTING: Retrospective analysis of subjects in well-characterized cohorts, the AIDS Clinical Trials Group (ACTG) 343 trial of induction-maintenance therapy (August 1997 to November 1998) and the Merck 035 trial (ongoing since March 1995). PATIENTS: Two hundred forty-one ACTG 343 patients, of whom 101 received triple-drug therapy throughout the study, and a small group of 13 patients from Merck 035 having virologic suppression after 6 months of indinavir-zidovudine-lamivudine. MAIN OUTCOME MEASURES: Association of intermittent viremia (plasma HIV RNA >50 copies/mL with a subsequent measure <50 copies/mL) with virologic failure (2 consecutive plasma HIV RNA measures >200 copies/mL) in both study groups; evidence of drug resistance in 7 patients from the small (n = 13) study group with long-term follow-up. RESULTS: Intermittent viremia occurred in 96 (40%) of the 241 ACTG 343 patients of whom 32 (13%) had 2 consecutive HIV RNA values >50 copies/mL during the median 84 weeks of observation (median duration of observation after first intermittent viremia episode was 46 weeks). Of the 101 individuals receiving triple-drug therapy throughout, 29% had intermittent viremia; the proportion of episodes occurring during the maintenance period was 64% for the entire cohort and 68% for the group not receiving triple-drug therapy throughout vs 55% for those who did (P =.25). Intermittent viremia did not predict virologic failure: 10 (10.4%) of 96 patients with and 20 (13.8%) of 145 patients without intermittent viremia had virologic failure (relative risk, 0.76; 95% confidence interval [CI], 0.29-1.72). In a Cox proportional hazards model, the risk for virologic failure was not significantly greater in the ACTG 343 patients with intermittent viremia (hazard ratio, 1.28; 95% CI, 0.59-2.79). Median viral load in 10 ACTG 343 patients assessed between 24 and 60 weeks of therapy using an ultrasensitive 2.5-copies/mL detection level assay was 23 copies/mL in those with intermittent viremia vs <2.5 copies/mL in those without (P =.15). Intermittent viremia occurred in 6 of 13 patients from the small study group assessed after 76 to 260 weeks of therapy (using the 2.5-copies/mL detection level assay) and was associated with a higher steady state of viral replication (P =.03), but not virologic failure over 4.5 years of observation. Viral DNA sequences from 7 patients did not show evolution of drug resistance. CONCLUSIONS: Intermittent viremia occurred frequently and was associated with higher levels of replication (Merck 035), but was not associated with virologic failure in patients receiving initial combination therapy of indinavir-zidovudine-lamivudine (ACTG 343 and Merck 035). In this population, treatment changes may not be necessary to maintain long-term virologic suppression with low-level or intermittent viremia.

Anti-HIV Agents↗
PubMed2000

Baseline human immunodeficiency virus type 1 phenotype, genotype, and RNA response after switching from long-term hard-capsule saquinavir to indinavir or soft-gel-capsule saquinavir in AIDS clinical trials group protocol 333.

AIDS Clinical Trials Group protocol 333 was an open-label trial of a switch from saquinavir (SQV) hard capsules (SQVhc) to indinavir (IDV) or saquinavir soft-gel capsules (SQVsgc) after >48 weeks of prior treatment with SQVhc. Eighty-nine subjects received IDV or SQVsgc or continued to receive SQVhc and continued unchanged treatment with non-protease-inhibitor antivirals for 8 weeks. Subjects receiving SQVhc then switched treatment to IDV. Baseline drug susceptibility and protease gene sequencing were done; 12 codons related to IDV and SQV resistance were analyzed. After 112 weeks (median) of SQVhc, the fall in human immunodeficiency virus (HIV) type 1 RNA level from baseline was significantly greater with IDV and was inversely correlated with the number of protease substitutions. The number of substitutions also correlated with baseline CD4 cell count, HIV-1 RNA level, SQV experience, and drug susceptibility. Substitution at codon 10, which occurred only in isolates with >/=2 substitutions, was associated with blunted RNA response. IDV IC(50) correlated with HIV-1 RNA response after the switch to IDV but added little predictive power once the genotype was considered.

Adolescent↗
PubMed1999

Efficacy and safety of delavirdine mesylate with zidovudine and didanosine compared with two-drug combinations of these agents in persons with HIV disease with CD4 counts of 100 to 500 cells/mm3 (ACTG 261). ACTG 261 Team.

To evaluate the antiretroviral activity of delavirdine mesylate, a non-nucleoside reverse transcriptase inhibitor of HIV-1, we performed a phase II, randomized, double-blind, multicenter trial comparing the three-drug combination of delavirdine with zidovudine and didanosine to two-drug combinations of these drugs. Patients with CD4 cell counts between 100 and 500 cells/mm3 without prior or <6 months of monotherapy with zidovudine or didanosine were randomized to one of four arms and observed on a follow-up basis for 48 weeks. In total, 544 patients were evaluated. In those assigned to the three-drug regimen, mean short-term (weeks 4-12) and long-term (weeks 40-48) change in CD4 cells from baseline were 49.3+/-8.1 and 65.4+/-13.4 cells/mm3, respectively; mean short-term and long-term HIV-1 RNA changes from baseline were -1.13 log10+/-0.12 and -0.73+/-0.12 copies/ml, respectively. These responses in CD4 cell counts and HIV-1 RNA levels were better in comparisons with each of the two-drug arms at all study points; however, differences were not consistently significant. Gastrointestinal side effects were experienced by 33% of patients (178 of 544), and 30% (121 of 407) receiving delavirdine experienced rash, only one case of which was severe. In this study, therapy with delavirdine + zidovudine + didanosine was safe and showed modest, but not always significant, antiviral activity and CD4 cell count benefit compared with two-drug regimens with these agents. Key

Adult↗
PubMed1999

Lamivudine in combination with zidovudine, stavudine, or didanosine in patients with HIV-1 infection. A randomized, double-blind, placebo-controlled trial. National Institute of Allergy and Infectious Disease AIDS Clinical Trials Group Protocol 306 Investigators.

OBJECTIVE: To study the antiviral activity of lamivudine (3TC) plus zidovudine (ZDV), didanosine (ddl), or stavudine (d4T). DESIGN: Randomized, placebo-controlled, partially double-blinded multicenter study. SETTING: Adult AIDS Clinical Trials Units. PATIENTS: Treatment-naive HIV-infected adults with 200-600x10(6) CD4 T lymphocytes/l. INTERVENTIONS: Patients were openly randomized to a d4T or a ddl limb, then randomized in a blinded manner to receive: d4T (80 mg/day), d4T plus 3TC (300 mg/day), or ZDV (600 mg/day) plus 3TC, with matching placebos; or ddl (400 mg/day), ddl plus 3TC (300 mg/day), or ZDV (600 mg/day) plus 3TC, with matching placebos. After 24 weeks 3TC was added for patients assigned to the monotherapy arms. MAIN OUTCOME MEASURE: The reduction in plasma HIV-1 RNA level at weeks 24 and 48. RESULTS: Two hundred ninety-nine patients were enrolled. After 24 weeks the mean reduction in plasma HIV-1 RNA copies/ml from baseline was 0.49 log10 (d4T monotherapy) versus 1.03 log10 (d4T plus 3TC; P = 0.001), and 0.68 log10 (ddl monotherapy) versus 0.82 log10 (ddl plus 3TC; P>0.22). After 48 weeks the mean reduction was 1.08 log10 (d4T plus 3TC) versus 1.01 log10 (ZDV plus 3TC) in the d4T limb (P = 0.66), and 0.94 log10 (ddl plus 3TC) versus 0.88 log10 (ZDV plus 3TC; P = 0.70) in the ddl limb. CONCLUSIONS: 3TC added significantly to the virologic effects of d4T, but not ddl, in treatment-naive patients. 3TC plus d4T produced virologic changes comparable to those of 3TC plus ZDV. These results support the use of 3TC with either ZDV or d4 as a component of initial combination antiretroviral therapy.

Adult↗
PubMed1997

Predictors and impact of patients lost to follow-up in a long-term randomized trial of immediate versus deferred antiretroviral treatment.

We studied predictors for losses to follow-up and the impact of such losses in the AIDS Clinical Trials Group 019 protocol, a long-term randomized trial of immediate versus deferred antiretroviral therapy in asymptomatic HIV-1-infected patients with >500 CD4 cells/mm3. The trial was selected because of its key importance in determining guidelines for antiretroviral therapy, and because it had the longest follow-up among all antiretroviral trials and the largest percentage of patients whose vital status was unknown at study end. Younger age, a history of parenteral drug use, and nonwhite race were associated with higher rates of loss to follow-up, but race was not an important predictor after adjusting for clinical site. There was large and statistically significant variability in the rates of losses among different clinical sites (p < 0.001). Patient retention was significantly better in clinical sites that enrolled many participants, with 25% of enrollees lost to follow-up in sites enrolling >100 patients and 44% in sites enrolling <33 patients each. As a group, patients lost to follow-up after the 2nd year had steeper declines of CD4 cell counts, and a significantly larger proportion had reached a CD4 cell count <300/mm3 in the year before being lost, compared with patients remaining in the study. Losses to follow-up probably decreased substantially the observed number of primary endpoints, curtailed the power of the trial to demonstrate any difference between immediate and deferred initiation of antiretroviral therapy, and may have introduced large bias in the estimated hazard ratio for the primary endpoint and its statistical significance.

Adult↗
PubMed1997

Squamous cell carcinomas of the head and neck cultured in floating collagen gels: 1. The maintenance of stromal and epithelial elements in vitro without fibroblast overgrowth.

The study of the molecular biology of head and neck squamous cell carcinomas has been heavily reliant on the analysis of cell lines. This is largely because the maintenance of primary cell cultures is difficult. However, being monoclonal, cell lines are not representative of the primary tumor because of the loss of tumor cell heterogeneity. We report a technique for primary culture of squamous cell carcinomas with maintenance of epithelial and stromal cell components without overgrowth of the fibroblast cells. Phenotypic markers for fibroblasts and squamous cells were present up to 45 days after initiation of culture, and expression of epidermal growth factor receptor and involucrin in cultures paralleled that in the primary tumor. In vivo, tumor stromal elements are thought to play an important role in the support of epithelial cell growth. In the collagen gel system the preservation of the stromal cell component likely improves culture viability and growth. More importantly, this culture system allows the in vitro tumor to more accurately reflect the tumor from which it was derived, and it permits the study of primary squamous cell carcinomas under in vitro conditions.

Antibodies, Monoclonal↗
PubMed1996

Combination therapy with zidovudine, didanosine and saquinavir.

The goal of AIDS Clinical Trials Group (ACTG) Protocol 229 was to evaluate the shorter term (24 week) and longer term (48 week) safety and activity of the HIV-1 proteinase inhibitor saquinavir in combination with zalcitabine (ddC) and zidovudine (ZDV) versus saquinavir in combination with ZDV versus ddC in combination with ZDV. This study confirms and extends the conclusions from the first 24 weeks of this study and showed that in subjects with extensive prior antiretroviral experience, the triple combination of saquinavir, ddC and ZDV was well-tolerated, safe and remained superior to the other double drug regimens as measured by CD4+ cell counts, quantitative HIV-1 microculture and plasma HIV-1 RNA levels.

Antiviral Agents↗
PubMed1996

Myoepithelial cells actively proliferate during atrophy of rat parotid gland.

Despite limited supporting evidence, salivary gland myoepithelial cells are said to be differentiated cells with little or no capacity to replicate; they presumably develop from stem cells. This study investigated the proliferative potential of myoepithelial cells with an antibody to proliferating cell nuclear antigen and a rat model. This model involved clamping of the parotid duct causing atrophy of the gland and then releasing the duct followed by gland regeneration. Rats were sacrificed at time points during atrophy and regeneration phases and the number and location of cycling myoepithelial cells assessed. Cycling myoepithelial cells were identified with double immunohistochemical staining, cycling cells with proliferating cell nuclear antigen-positive nuclei within muscle-specific actin-positive cytoplasm (the latter identified with antibody HHF35). The results show that baseline proliferative rates of myoepithelial cells in both the resting and fully regenerated gland ranged from 0.3% to 2%, similar to rates for other major cell types in the normal rat gland. A peak myoepithelial cell proliferative rate of 23% occurred at day 5 during the atrophy phase. Rates during the regenerative phase were not significantly different than the baseline levels. Similarities of rat and human parotid gland and the definite proliferative capacity of myoepithelial cells indicates that these specialized cells must be considered one of the potential progenitor cells for human salivary gland tumors.

Actins↗
PubMed1994

Prevalence and patterns of use of concomitant medications among participants in three multicenter human immunodeficiency virus type I clinical trials. AIDS Clinical Trials Group (ACTG).

Data on the prevalence and patterns of use of concomitant medications among participants in three large phase III clinical trials of zidovudine (ZDV) in human immunodeficiency virus type 1 (HIV-1) infection were analyzed. Overall, 2,801 patients reported 43,331 uses of concomitant medications. Over 85% of clinical trial participants used one or more concomitant medications at some point during the study. Patients with acquired immune deficiency syndrome (AIDS) used an average of 7.1 drugs per month. Patients with AIDS-related complex (ARC) or who were asymptomatic used relatively fewer drugs: 3.1 and 2.7 per month, respectively. Fourteen percent of patients with AIDS used more than 10 concomitant medications per month. The three most commonly utilized classes of drugs were antiinfectives (57%), analgesics or antipyretics (55%), and vitamins (47%). A total of 17% of patients overall and 30% of AIDS patients used acyclovir while on trial. Consumption of prescription drugs was greater, and "over-the-counter" drugs less, among AIDS patients. Reported use of agents not approved by the Food and Drug Administration or approved drugs used for off-label indications was infrequent. Overall use of concomitant medications did not differ across demographic subgroups when corrected for disease stage at the time of enrollment. White, non-Hispanic, homosexual and bisexual men consumed significantly more antivirals and vitamins than other trial participants. Women in all three protocols took more analgesics or antipyretics than did men.(ABSTRACT TRUNCATED AT 250 WORDS)

AIDS-Related Complex↗