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Biomedical subjects

B Yip

Publications and source records attributed to B Yip.

At least 37 records · Page 2Linked to original sources
PubMed1998

The antiviral effect of ritonavir and saquinavir in combination amongst HIV-infected adults: results from a community-based study.

OBJECTIVE: To characterize the antiviral effect and predictors of response to ritonavir and saquinavir-based antiretroviral combination therapy. DESIGN: Intent-to-treat analysis with suppression of plasma viral load to levels below 2.7 log10 copies/ml as the main outcome measure. PATIENTS: All adult HIV-positive individuals in the province of British Columbia who started taking ritonavir and saquinavir (each at 600 mg twice daily) in combination from 1 September 1996 to 28 February 1997, with a minimum of two plasma viral load measurements, one at baseline and one after the initiation of therapy. RESULTS: A total of 58 participants were prescribed ritonavir and saquinavir. The median plasma viral load at entry was 4.80 log10 copies/ml (interquartile range, 4.51-5.15 log10 copies/ml). A total of 29 (50%) subjects demonstrated a decrease in plasma viral load to levels below 2.7 log10 copies/ml. This level of suppression was associated with higher baseline CD4 cell counts (P=0.022) and no prior exposure to protease inhibitors (P=0.001). After controlling for baseline CD4 cell count and plasma viral load, participants naive to protease inhibitors were almost seven times (odds ratio, 6.99; 95% confidence interval, 1.85-26.39; P=0.004) more likely to suppress their plasma viral load to below 2.7 log10 copies/ml than those who had previously used protease inhibitors. CONCLUSION: Our analysis demonstrates that a ritonavir and saquinavir-based combination can produce a substantial decrease in plasma viral load with half of the participants decreasing their plasma viral load to below the limit of quantification of the assay. This response, however, is seriously compromised by prior exposure to protease inhibitors.

Adult↗
PubMed1998

Antiviral effect of double and triple drug combinations amongst HIV-infected adults: lessons from the implementation of viral load-driven antiretroviral therapy.

OBJECTIVE: To study the antiviral effect and predictors of response to two- and three-drug regimens amongst antiretroviral-naive individuals using an intent-to-treat analysis. MAIN OUTCOME MEASURE: Suppression of plasma viral load to < 500 copies/ml. PATIENTS: A total of 420 (264 double drug, 156 triple drug) individuals in a province-wide treatment programme were studied. RESULTS: A decrease in plasma viral load to < 500 copies/ml was documented in 197 (47%) subjects. This was independently associated with a lower baseline plasma viral load (odds ratio, 3.67; 95% confidence interval, 2.13-6.30) and initiation onto a three-drug regimen (odds ratio, 3.86; 95% confidence interval, 2.24-6.66). Median plasma viral load failed to reach < 500 copies/ml and in fact rebounded in the two-drug group. In contrast, 91 (58%) subjects receiving three drugs reached < 500 copies/ml during the study period. CONCLUSION: These results support the use of powerful triple drug regimens as initial therapy in HIV-infected individuals.

Adult↗
PubMed1998

Improved survival among HIV-infected individuals following initiation of antiretroviral therapy.

CONTEXT: Clinical trials have established the efficacy of antiretroviral therapy with double- and triple-drug regimens for individuals infected with the human immunodeficiency virus (HIV), but the effectiveness of these regimens in the population of patients not enrolled in clinical trials is unknown. OBJECTIVE: To characterize survival following the initiation of antiretroviral therapy among HIV-infected individuals in the province of British Columbia. DESIGN: Prospective, population-based cohort study of patients with antiretroviral therapy available free of charge (median follow-up, 21 months). SETTING: Province of British Columbia, Canada. PATIENTS: All HIV-positive men and women 18 years of age or older in the province who were first prescribed any antiretroviral therapy between October 1992 and June 1996 and whose CD4+ cell counts were less than 0.350 x 10(9)/L. MAIN OUTCOME MEASURES: Rates of progression from initiation of antiretroviral therapy to death or a primary acquired immunodeficiency syndrome (AIDS) diagnosis for subjects who initially received zidovudine-, didanosine-, or zalcitabine-based therapy (ERA-I) and for those who initially received therapy regimens including lamivudine or stavudine (ERA-II). RESULTS: A total of 1178 patients (951 ERA-I, 227 ERA-II) were eligible. A total of 390 patients died (367 ERA-I, 23 ERA-II), yielding a crude mortality rate of 33.1%. ERA-I group subjects were almost twice as likely to die as ERA-II group subjects, with a mortality risk ratio of 1.86 (95% confidence interval [CI], 1.21 -2.86; P=.005). After adjusting for Pneumocystis carinii and Mycobacterium avium prophylaxis use, AIDS diagnosis, CD4+ cell count, sex, and age, ERA-I participants were 1.93 times (95% CI, 1.25-2.97; P=.003) more likely to die than ERA-II participants. Among patients without AIDS when treatment was started, ERA-I participants were 2.50 times (95% CI, 1.59-3.93; P<.001) more likely to progress to AIDS or death than ERA-II participants. CONCLUSION: The HIV-infected individuals who received initial therapy with regimens including stavudine or lamivudine had significantly lower mortality and longer AIDS-free survival than those who received initial therapy with regimens limited to zidovudine, didanosine, and zalcitabine.

AIDS-Related Opportunistic Infections↗
PubMed1998

Hemophilia B in a female carrier due to skewed inactivation of the normal X-chromosome.

A novel missense mutation (codon 351, GCT (Ala) --> CCT (Pro)) of the FIX gene was characterised in a young female with mild hemophilia B. She is heterozygous for the FIX mutation inherited from her carrier mother. Analysis of the methyl-sensitive Hpa II sites at the 5' end of the hypoxanthine phosphoribosyltransferase gene showed that skewed inactivation of the X chromosome carrying her normal FIX gene accounted for the hemophilia phenotype.

Adult↗
PubMed1998

The incidence and spectrum of AIDS-defining illnesses in persons treated with antiretroviral drugs.

The incidence and spectrum of primary AIDS-defining illnesses in human immunodeficiency virus-positive patients receiving antiretroviral drugs may have changed since the introduction of newer antiretroviral agents. We performed a retrospective analysis of patients enrolled in the British Columbia Drug Treatment Program who were ever prescribed antiretroviral drugs between 1 January 1994 and 31 December 1996. Rates were calculated on a 6-month basis. There were 344 AIDS cases diagnosed among 2,533 participants between 1994 and 1996. The incidence of primary AIDS diseases decreased from 1994 to 1996, with a sharp decline in 1995 and 1996. There was no statistically significant change in the incidence of primary AIDS diagnoses relative to one another, and Pneumocystis carinii pneumonia and Kaposi's sarcoma remain the most common AIDS index diagnoses. In patients receiving antiretroviral therapy in the modern era, the incidence of AIDS-defining illnesses has decreased substantially, but the spectrum of AIDS-defining illnesses remains unchanged.

Acquired Immunodeficiency Syndrome↗
PubMed1998

Do dual nucleoside regimens have a role in an era of plasma viral load-driven antiretroviral therapy?

This study was undertaken to characterize predictors of response to double nucleoside combinations among 245 human immunodeficiency virus-infected persons initiating antiretroviral therapy. The median time for receiving antiretroviral therapy in this group was 6 months, and the plasma virus load was 58,000 copies/mL. The most commonly prescribed regimens were zidovudine/lamivudine (154 subjects, 63%) and stavudine/lamivudine (46 subjects, 19%). A total of 96 (39%) subjects had their virus load decrease to < 500 copies/mL after the initiation of therapy. Of the 245 study subjects, 102 (41.6%) had > or = 5 months of follow-up and two or more consecutive virus load determinations performed after the start of antiretroviral therapy. Multivariate analysis demonstrated that baseline virus load was the only significant factor associated with obtaining two or more plasma virus loads of < 500 copies/mL. Overall, these data demonstrate that dual nucleoside therapy (using currently licensed agents) cannot reliably achieve a high level of suppression of plasma virus load.

Adult↗
PubMed1998

Average annual drug cost and its determinants in a population based cohort of HIV-positive adult men and women.

The purpose of this study is to determine drug costs and the sociodemographic and clinical determinants of drug costs in a large open cohort of HIV-positive adult men and women in British Columbia, Canada from 1993 to 1995. The study is descriptive and population-based using time-series data. Individuals included in the study were men and women enrolled in a province-wide HIV/AIDS drug treatment programme who had given consent to access their entire prescription records held by the provincial drug plan. The primary outcome measure was the average annual drug cost for treating HIV/AIDS among programme participants; results were stratified by sociodemographic status, drug category and disease severity. The analysis was restricted to 1271 consenting programme participants. The average annual drug cost per participant in 1996 Canadian dollars ($Can) was $Can3431 in 1993, $Can3892 in 1994 and $Can4377 in 1995. Between 1993 and 1995, the average annual cost of antiretroviral therapies increased by 6.6% ($Can2579 in 1995), anti-infectives increased by 61.4% ($Can2402 in 1995) and other drugs used in the management of patients with HIV disease increased by 35.7% ($Can1146 in 1995). The overall increase over this period was 27.6%. In 1995, the average annual drug cost was $Can4720 for those on social assistance, $Can4545 for seniors and $Can5937 for the general population (nonpoor and nonelderly). In 1995, the average annual drug cost was $Can6887 for those with AIDS and $Can3911 for those without. Multivariate modelling indicated that drug costs were significantly related with CD4+ cell count (p < 0.001), diagnoses of AIDS (p < 0.001), provincial drug plan type (p = 0.002), time participants had spent in the HIV/AIDS Drug Treatment Program (p = 0.003), number of hospitalisations (p = 0.003) and patient's age (p = 0.004). Our data demonstrate that the average annual drug costs for persons with HIV/AIDS in British Columbia have been increasing even though the cost of antiretrovirals has been relatively stable. This was due mainly to the increase in the cost of anti-infectives and other drugs. Important cost drivers were participant's age, socioeconomic status (by provincial drug insurance coverage level) and rate of disease progression as measured by CD4+ cell counts, hospitalisation events and duration of illness.

Adult↗
PubMed1998

Modelling the potential economic impact of viral load-driven triple drug combination antiretroviral therapy.

The purpose of this study is to model the potential economic impact of viral load-driven triple drug combination (including a protease inhibitor) antiretroviral therapy on incremental drug and hospitalisation costs among individuals with HIV disease. Individuals included in the study were HIV-positive men and women from the province of British Columbia, Canada, who were aged 18 years or older and had given consent to access their medical records. The study employed pharmacoeconomic modelling of drug- and hospital-utilisation patterns among a population-based cohort with free access to antiretroviral therapy. Protease inhibitor use and associated costs based on actual use in a subsequent period was modelled upon men and women who were able to maintain stable CD4+ cell counts (slope > or = 0) for at least 6 months (baseline period) with an average follow-up period of 30 months (protease-like group). A control was modelled upon individuals with declining CD4+ cell counts (slope < 0) during similar baseline and follow-up periods. The primary outcome measure was average annual incremental cost of triple drug therapy net of hospitalisation and testing costs in 1996 Canadian dollars ($Can). The utilisation pattern of drugs and hospitals was modelled from actual use among a total of 1271 individuals who were eligible for this analysis. Programme participants who gave consent to access their medical records were more likely to be men (p < 0.001), older (p < 0.020), and on antiretroviral therapy (p < 0.001) than programme participants who did not give consent. No differences were observed between the protease-like and comparison groups with respect to age (p = 0.65) and CD4+ cell count (p = 0.30) at study entry. Over a period of 1 year, the protease-like group was shown to spend less time in hospital (2.7 vs 6.6 days; p < 0.001). This difference in hospitalisation remained in multivariate models, adjusting for prior AIDS-defining illnesses and gender. The average annual incremental cost of adding a protease inhibitor to a 2-drug antiretroviral regimen was estimated to be $Can2318 per person. The cost implications of hospital stay while using a protease inhibitor drug and 2 nucleosides translated into an average annual incremental cost (savings if negative) of between -$Can4798 and -$Can2227 per person. The overall average annual incremental cost impact per person associated with triple drug therapy with a protease inhibitor varied between -$Can2288 to $Can283. Negative incremental costs imply overall savings from adopting triple combination therapy. This modelling exercise demonstrated that the cost of triple drug combination antiretroviral therapy with a protease inhibitor among HIV-positive men and women was considerably less than the expected acquisition cost of the drug alone due to hospitalisation savings in the province of British Columbia.

Adult↗
PubMed1997

Expression of stable human O-glycan core 2 beta-1,6-N-acetylglucosaminyltransferase in Sf9 insect cells.

UDP-GlcNAc:Galbeta1-3GalNAc-R (GlcNAc to GalNAc) beta-1, 6-N-acetylglucosaminyltransferase (C2GnT) catalyses the formation of O-glycan core 2. Purification and characterization of C2GnT from natural sources has been hampered by the instability of this enzyme. We have been able to prepare a stable partly purified recombinant human C2GnT by expression of a truncated form of the enzyme in the baculovirus/Spodoptera frugiperda 9 (Sf9) insect cell system. C2GnT activity was secreted into the Sf9 culture medium (15 pmol/min per microl; approx. 0.2 mg/l) and was stable at 4 degrees C either in solution or after lyophilization. Endoglycosidase H and N-glycanase F treatment of the radiolabelled C2GnT indicated the presence of N-glycans at both potential N-glycosylation sites. The elimination of one or both of the two potential N-glycosylation sites or treatment of the virus-infected insect cells with tunicamycin resulted in loss of enzyme activity due in part to protein degradation.

Animals↗
PubMed1997

Organization of the human beta-1,2-N-acetylglucosaminyltransferase I gene (MGAT1), which controls complex and hybrid N-glycan synthesis.

UDP-GlcNAc: alpha-3-D-mannoside beta-1,2-N-acetylglucosaminyltransferase I (EC 2.4.1.101; GlcNAc-T I) is a medial-Golgi enzyme which catalyses the first step in the conversion of oligomannose-type to N-acetyl-lactosamine- and hybrid-type N-glycans and is essential for normal embryogenesis in the mouse. Previous work indicated the presence of at least two exons in the human GlcNAc-T I gene MGAT1, exon 2 containing part of the 5' untranslated region and the complete coding and 3' untranslated regions, and exon 1 with the remainder of the 5' untranslated region. We now report the cloning and sequencing of a human genomic DNA fragment containing exon 1, which is between 5.6 and 15 kb upstream of exon 2. Transient transfection, ribonuclease protection and reverse transcriptase-mediated PCR indicated the absence of transcription start sites in intron 1 between exons 1 and 2. Northern analysis, ribonuclease protection, primer extension analysis and rapid amplification of 5'-cDNA ends showed that there are multiple transcription start sites for exon 1 compatible with the expression by several human cell lines and tissues of two transcripts, a broad band ranging in size from 2.7 to 3.0 kb and a sharper band at 3.1 kb. The 5' flanking region of exon 1 has a GC content of 81% and has no canonical TATA or CCAAT boxes but contains potential binding sites for transcription factors Sp1, GC-binding factor and epidermal growth factor receptor-specific transcription factor. Chloramphenicol acetyltransferase (CAT) expression was observed on transient transfection into HeLa cells of a fusion construct containing the gene for CAT and a genomic DNA fragment from the 5' flanking region of exon 1. It is concluded that MGAT1 is a typical housekeeping gene although there is, in addition, tissue-specific expression of the larger 3.1 kb transcript.

Base Sequence↗
PubMed1997

HIV/AIDS care giving physicians: their experience and practice patterns.

To identify associations between HIV-related experience and patterns of service provision, physicians across Canada were solicited by mail to register in a national network of HIV/AIDS care givers. Respondents provided data about: personal, demographic and practice characteristics; the number of HIV-positive patients ever seen; the nature of the HIV-positive client population; and services provided to HIV-positive patients. Univariate techniques provided a demographic and professional profile of participating physicians. Logistic regression was used to identify associations between level of HIV-related experience and the provision of patient services. The 566 registered physicians have provided care to 56,378 HIV-infected persons and represent every province and territory in Canada. Multivariate analysis revealed that highly experienced physicians were more likely to provide all 3 types of services considered, to practise in Montreal, Vancouver or Toronto, and to be medical specialists (all P < 0.001).

Acquired Immunodeficiency Syndrome↗
PubMed1997

Diabetic papillopathy: two case reports in individuals with adult onset diabetes mellitus.

BACKGROUND: Diabetic papillopathy is a benign unilateral or bilateral optic neuropathy with transient optic disk edema and minimal reduction in visual function. The optic disk edema typically resolves in a few months with no resulting optic atrophy and minimal or no decrease in acuity. The exact etiology of the disk edema is unknown, but theories include retinal vascular leakage into and surrounding the optic nerve and disruption of axoplasmic flow resulting from microvascular disease of the optic nerve head vasculature. CASE REPORTS: Two adult patients receiving insulin for type II diabetes mellitus manifested bilateral disk edema and minimal visual dysfunction. Both patients showed funduscopic evidence of mild-to-moderate nonproliferative diabetic retinopathy O.D. and O.S., and one patient had clinically significant macular edema in both eyes. The diagnosis in both cases was diabetic papillopathy. Both patients had significant resolution of their disk edema in 3 to 6 months, with stable acuities and no signs of optic atrophy. CONCLUSIONS: Although diabetic papillopathy is a well-known clinical entity in patients with type I diabetes, the clinical profile can be expanded to include individuals with type II diabetes.

Adult↗
PubMed1996

A semi-automated method for analysis of intron 13 and intron 22 dinucleotide repeat polymorphisms of the factor VIII gene.

A semi-automated method has been developed for the simultaneous analysis of two micro-satellite repeat polymorphisms located in intron 13 and 22 of the Factor VIII gene. The fluorescent dyes, 6-FAM-and HEX-phosphoramidites were used to 5'-end label the respective 5' primers of these two microsatellite repeats and a multiplex polymerase chain reaction (PCR) devised for amplification. The PCR product was loaded onto the gel with DNA size marker labelled with ROX. A total of 24 samples could be analysed simultaneously on an automated DNA sequencer. The results were computed using a dedicated software, with assignment of PCR product size in basepair. This method compares well with the conventional manual procedure using radio-labelled primers, but at the same time overcomes many of the inherent disadvantages associated with the latter method.

Alleles↗