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Biomedical subjects

D K Li

Publications and source records attributed to D K Li.

At least 19 recordsLinked to original sources
PubMed2001

Randomized controlled trial of interferon-beta-1a in secondary progressive MS: MRI results.

OBJECTIVE: To examine MRI changes resulting from treatment of secondary progressive MS (SPMS) with two doses of interferon-beta-1a (Rebif). BACKGROUND: Interferon-beta (IFN-beta) reduces relapses and delays progression in relapsing-remitting MS, but there are conflicting results on its clinical benefit in SPMS. METHODS: In a double-blind, randomized, multicenter, placebo-controlled study (SPECTRIMS), 618 patients received IFN-beta-1a 22 microg, 44 microg, or placebo subcutaneously three times weekly for 3 years. T2 activity and burden of disease (BOD) were measured in 617 patients by using semiannual proton density/T2-weighted (PD/T2) MRI scans. A cohort of 283 patients also had 11 monthly PD/T2 and T1-weighted gadolinium-enhanced (T1-Gd) scans at study start. RESULTS: Treatment reduced median numbers of active lesions per patient per scan (semiannual T2 activity: 0.17, 0.20 and 0.67 for the high dose, low dose, and placebo, p < 0.0001; monthly combined unique activity [T1+T2]: 0.11, 0.22, and 1.00, p < 0.0001) and accumulation of BOD (percent change from baseline to month 36: -1.3, -0.5, and 10.0 for the high dose, low dose, and placebo, respectively; p = 0.0001). MRI benefit was most evident in the subgroup of patients who reported relapses in the 2 years before the study. Neutralizing antibody development was associated with reduction in treatment effect: antibody-positive patients did not show significant differences from placebo at either dose. CONCLUSIONS: Interferon-beta-1a used in SPMS showed significant effects on all MRI measures, particularly in patients with relapses in the 2 years before the study.

Adjuvants, Immunologic↗
PubMed2001

Regional cerebral glucose metabolism in never-medicated patients with schizophrenia.

OBJECTIVE: The purpose of this study was to assess regional cerebral glucose metabolism in patients with schizophrenia who had never received antipsychotic medication and whose olfactory identification ability had been assessed. Two hypotheses were examined. First, the patients were compared with normal controls to determine whether differences in regional cerebral metabolism were apparent. Second, regional rates of metabolism were correlated with olfactory ability and the relation between them determined. METHODS: The patient (n = 26) and control (n = 32) subjects were scanned at rest using positron emission tomography (PET) after administration of 18F-fluorodeoxyglucose (FDG). In addition, the University of Pennsylvania Smell Identification Test was administered to each patient. RESULTS: Patients with schizophrenia had reduced rates of glucose metabolism in the right and left thalamus that reached significance if not corrected for multiple comparisons. However, if a Bonferroni correction was applied over the 27 regions of interest, the differences were not significant. Scores on the Smell Identification Test were negatively correlated with 8 regions of interest. When scores were analyzed using multiple regression, the left frontal cortex and the medial parietal cortex were significant predictors. CONCLUSIONS: The finding of reduced metabolism in the thalami is consistent with some of the previous literature, whereas the negative correlations between specific regions and olfactory function are not consistent with studies using activation paradigms.

Adolescent↗
PubMed2001

[Studies on the pharmacokinetics and relative bioavailability of salbutamol aerosol in healthy volunteers].

AIM: To study the pharmacokinetics and relative bioavailability of salbutamol aerosol in healthy volunteers. METHODS: An HPLC method for the determination of salbutamol in human plasma was improved. Ten healthy male subjects were enrolled. A randomized, two-way crossover, open design was adopted. After the subjects inhaled or orally administered salbutamol, fourteen blood samples were taken at predetermined time. The concentrations of salbutamol in plasma were determined by HPLC, and then assessed with PCNONLIN software to obtain the pharmacokinetic parameters and relative bioavailability of aerosol versus water solution. RESULTS: The standard curve was linear over the range 0.2-20 ng.mL-1. The intra- and interassay RSDs were 7.01% and 2.10% at 0.4 ng.mL-1, 2.18% and 5.25% at 4.0 ng.mL-1 and 4.61% and 4.85% at 15.0 ng.mL-1. The recoveries were between 90% and 110%. The pharmacokinetics of salbutamol aersol was described well with a two-compartment model, and the parameters for salbutamol inhaled and orally administered were assessed as follows: Tmax were (0.22 +/- 0.07) h and (1.8 +/- 0.6) h, Cmax were (3.4 +/- 1.1) ng.mL-1 and (3.9 +/- 1.4) ng.mL-1, T1/2 beta were (4.5 +/- 1.5) h and (4.6 +/- 1.1) h, respectively. The AUC0-20 min (inhal) was 7.94 times as high as the AUC0-20 min (p.o.). There were significant differences between Tmax, AUC, K12, K21, alpha and T1/2 alpha (P < 0.05). The relative bioavailability of salbutamol aerosol was 57.23% compared with its oral solution. CONCLUSION: The assay was sensitive, specific, accurate and precise. The absorption process of salbutamol aerosol in human was significantly different from that of the oral solution. It was demonstrated that AUC0-20 min reflected the lung availability of salbutamol inhaler.

Administration, Inhalation↗
PubMed2000

A pathology-MRI study of the short-T2 component in formalin-fixed multiple sclerosis brain.

OBJECTIVE: To determine the pathologic basis of areas not exhibiting signal of the short-T2 component of the T2 relaxation distribution in MS, as studied in formalin-fixed brain. BACKGROUND: A myelin-specific MRI signal would be of great importance in assessing demyelination in patients with MS. Evidence indicates that the short-T2 (10 to 50 millisecond) component of the T2 relaxation distribution originates from water in myelin sheaths. The authors present two cases of MS in which the anatomic distribution of the short-T2 component was correlated with the pathologic findings in postmortem formalin-fixed brain. METHOD: One half of the formalin-fixed brain was suspended in a gelatin-albumin mixture cross-linked with glutaraldehyde, and scanned with a 32-echo MRI sequence. The brain was then cut along the center of the 5-mm slices scanned, photographed, dehydrated, and embedded in paraffin. Paraffin sections, stained with Luxol fast blue and immunocytochemically for 2',3'-cyclic nucleotide 3'-phosphohydrolase for myelin and by the Bielschowsky technique for axons, were compared with the distribution of the amplitude of the short-T2 component of the comparable image slices. RESULTS: The anatomic distribution of the short-T2 component signal corresponded to the myelin distribution. Chronic, silent MS plaques with myelin loss correlated with areas of absence of short-T2 signal. The numbers of axons within lesions were reduced, but many surviving axons were also seen in these areas of complete loss of myelin. CONCLUSION: In formalin-fixed MS brains the short-T2 component of the T2 relaxation distribution corresponds to the anatomic distribution of myelin. Chronic, silent demyelinated MS plaques show absence of the short-T2 component signal. These results support the hypothesis that the short-T2 component originates from water related to myelin.-1510

Aged↗
PubMed2000

Effect of interferon beta-1b in MS: assessment of annual accumulation of PD/T2 activity on MRI. UBC MS/MRI Analysis Group and the MS Study Group.

OBJECTIVE: To determine whether the efficacy of interferon beta-1b (IFNbeta-1b) on lesion activity could be shown with annual analysis of MRI. BACKGROUND: Clinical outcomes and MRI burden of disease changes in MS patients in a multicenter double-blind placebo-controlled 5-year trial of IFNbeta-1b have been reported, together with an analysis of 6-weekly MRI activity in a small subgroup during 2 years. MRI activity measurements based on annual scans have not been documented. METHODS: Patients were randomized into three treatment arms: placebo, 1.6 mIU, and 8 mIU IFNbeta-1b self-administered subcutaneously every other day. Active lesions were identified as new, enlarging, or recurrent on proton density and T2-weighted MRI scans. Gadolinium was not used. An annual accumulation activity index was developed as an additional analysis of lesion activity. RESULTS: During the 5 years, both high- and low-dose IFNbeta-1b groups showed a striking reduction in lesion annual accumulation activity on the activity index versus placebo (p = 0.001). Thirty-five percent of the high-dose patients and 29% of the low-dose patients were MRI inactive by this method of analysis, whereas only 16% of placebo patients were inactive (p = 0.001, placebo versus 8 mIU). CONCLUSIONS: This analysis of the annual accumulation of lesion activity shows that the previously reported treatment effect seen on MRI scanning once every 6 weeks in a subcohort of the patients can also be seen on yearly scans. This annual accumulation activity analysis provides an independent MRI confirmation of a treatment and dose effect for IFNbeta-1b.

Cohort Studies↗
PubMed2000

Changing paternity and the risk of preeclampsia/eclampsia in the subsequent pregnancy.

To determine whether changing paternity affects the risk of preeclampsia or eclampsia in the subsequent pregnancy and whether the effect depends on a woman's history of preeclampsia/eclampsia with her previous partner, a cohort study was conducted based on 140,147 women with two consecutive births during 1989-1991 identified through linking of annual California birth certificate data. Among women without preeclampsia/eclampsia in the first birth, changing partners resulted in a 30% increase in the risk of preeclampsia/eclampsia in the subsequent pregnancy compared with those who did not change partners (95% confidence interval: 1.1, 1.6). On the other hand, among women with preeclampsia/eclampsia in the first birth, changing partners resulted in a 30% reduction in the risk of preeclampsia/eclampsia in the subsequent pregnancy (95% confidence interval: 0.4, 1.2). The difference of the effect of changing paternity on the risk of preeclampsia/eclampsia between women with and those without a history of this condition was significant (p < 0.05 for the interaction term). The above estimates were adjusted for potential confounders. These findings suggest that the effect of changing paternity depends on the history of preeclampsia/eclampsia with the previous partner and support the hypothesis that parental human leukocyte antigen sharing may play a role in the etiology of preeclampsia/eclampsia.

Adult↗
PubMed2000

Different magnetization transfer effects exhibited by the short and long T(2) components in human brain.

Magnetization transfer ratios (MTRs) were measured separately for the two T(2) components in white matter. For both binomial and off-resonance sinc MT pulses, the MTR was larger for the short T(2) component than for the long T(2) component. This differential MT effect disappeared for delays between the MT pulse and the multi-echo pulse sequence longer than 200 msec, indicating exchange between the two components. When using the sinc MT pulse, the MTR for the short T(2) component was similar for different white matter structures, whereas it varied for different white matter structures when using the binomial pulse-a phenomenon attributed to direct saturation. When the sinc pulse frequency was brought closer to resonance, MTRs in white matter and doped water phantoms increased for both components but more so for the shorter T(2) component. This behavior was consistent with a Bloch equation model of direct saturation.

Adolescent↗
PubMed2000

Maternal pre-eclampsia/eclampsia and the risk of sudden infant death syndrome in offspring.

To determine whether maternal exposure to pre-eclampsia/eclampsia during pregnancy increases the risk of sudden infant death syndrome (SIDS) in offspring, we conducted a population-based case-control study using the California linked birth and death certificate data. All infants who died of SIDS (ICD-9 code 798.0) during 1989-91 were identified as cases. More than 96% of the identified SIDS cases were diagnosed through autopsy. Ten controls who did not die from SIDS were randomly selected for each case from the birth certificate matched to the case on the year of birth. Among 2,029 cases and 21,037 controls included in the final analysis, mothers of 49 cases (2.4%) and 406 controls (1.9%) had a diagnosis of either pre-eclampsia or eclampsia noted on the birth certificate. After adjustment for maternal age, prenatal smoking, race/ethnicity, parity, maternal education, gestational age at the initial visit for prenatal care, infant year of birth and infant sex, maternal pre-eclampsia/ eclampsia during pregnancy was associated with a 50% increased risk of SIDS in the offspring (odds ratio = 1.5, 95% confidence interval 1.1, 2.0). Potential under-reporting of pre-eclampsia/eclampsia on the birth certificates was likely to be non-differential and is unlikely to explain the finding. Fetal hypoxia resulting from pre-eclampsia/ eclampsia or immunological aetiology affecting the risk of both pre-eclampsia/eclampsia and SIDS may explain the finding.

Adolescent↗
PubMed2000

Neonatal sepsis workups in infants >/=2000 grams at birth: A population-based study.

BACKGROUND: Few data are available on the outcome of neonatal sepsis evaluations in an era when intrapartum antibiotic therapy is common. METHODS: We identified all newborns weighing >/=2000 g at birth who were ever evaluated for suspected bacterial infection at 6 Kaiser Permanente hospitals between October 1995 and November 1996, reviewed their records and laboratory data, and tracked them to 1 week after discharge. We analyzed the relationship between key predictors and the presence of neonatal bacterial infection. RESULTS: Among 18 299 newborns >/=2000 g without major congenital anomalies, 2785 (15.2%) were evaluated for sepsis with a complete blood count and/or blood culture. A total of 62 (2.2%) met criteria for proven, probable, or possible bacterial infection: 22 (.8%) had positive cultures and 40 (1.4%) had clinical evidence of bacterial infection. We tracked all but 10 infants (.4%) to 7 days postdischarge. There were 67 rehospitalizations (2.4%; 2 for group B streptococcus bacteremia). Among 1568 infants who did not receive intrapartum antibiotics, initial asymptomatic status was associated with decreased risk of infection (adjusted odds ratio [AOR]:.26; 95% confidence interval [CI]:.11-.63), while chorioamnionitis (AOR: 2. 40; 95% CI: 1.15-5.00), low absolute neutrophil count (AOR: 2.84; 95% CI: 1.50-5.38), and meconium-stained amniotic fluid (AOR: 2.23; 95% CI: 1.18-4.21) were associated with increased risk. Results were similar among 1217 infants who were treated, except that maternal chorioamnionitis was not significantly associated with neonatal infection. CONCLUSIONS: The risk of bacterial infection in asymptomatic newborns is low. Evidence-based observation and treatment protocols could be defined based on a limited set of predictors: maternal fever, chorioamnionitis, initial neonatal examination, and absolute neutrophil count. Many missed opportunities for treating mothers and infants exist.

Ampicillin↗
PubMed2000

T2 hyperintensities: findings and significance.

The hyperintense lesions of multiple sclerosis seen on proton density- and T2-weighted MR images have important clinical and research roles in the diagnosis, follow-up, prognosis, and treatment of the disease.

Brain↗
PubMed2000

Nonlinear pharmacokinetics of paclitaxel in ovarian cancer patients.

AIM: To characterize the disposition of paclitaxel in patients with ovarian carcinoma after a 3-h infusion. METHODS: Fifteen patients with advanced ovarian cancer were enrolled and were administered paclitaxel in a 3-h infusion at dosing levels of 135 mg/m2, 175 mg/m2, and 235 mg/m2. Thirteen plasma samples were obtained during the infusion and up to 24 h after the infusion. Paclitaxel concentrations in plasma were determined by HPLC assay. Pharmacokinetic parameters were assessed with noncompartment model and model-dependent method. RESULTS: The disposition of paclitaxel in patients with ovarian cancer conformed to a two-compartment model. The main pharmacokinetic parameters of three groups were T1/2 beta (5.18 +/- 3.49), (6.26 +/- 2.21), and (6.99 +/- 1.45) h, AUC (14.71 +/- 0.76), (39.09 +/- 13.10), and (66.52 +/- 12.23) mg.h.L-1, Cl (14.29 +/- 0.74), (7.52 +/- 2.15), and (6.25 +/- 1.93) L.h-1, respectively. CONCLUSION: The disposition of paclitaxel was nonlinear after a 3-h infusion. There was individual variability of metabolism among patients.

Adult↗
PubMed1999

The contribution of magnetic resonance imaging to the diagnosis of multiple sclerosis.

MRI is very sensitive in showing MS lesions throughout the CNS. Using MRI for diagnostic purposes, however useful, is a complex issue because of limited specificity of findings and a variety of options as to when, how, and which patients to examine. Comparability of data and a common view regarding the impact of MRI are needed. Following a review of the typical appearance and pattern of MS lesions including differential diagnostic considerations, we suggest economic MRI examination protocols for the brain and spine. Recommendations for referral to MRI consider the need to avoid misdiagnosis and the probability of detecting findings of diagnostic relevance. We also suggest MRI classes of evidence for MS to determine the diagnostic weight of findings and their incorporation into the clinical evaluation. These proposals should help to optimize and standardize the use of MRI in the diagnosis of MS.

Brain↗
PubMed1999

Maternal placental abnormality and the risk of sudden infant death syndrome.

To determine whether placental abnormality (placental abruption or placental previa) during pregnancy predisposes an infant to a high risk of sudden infant death syndrome (SIDS), the authors conducted a population-based case-control study using 1989-1991 California linked birth and death certificate data. They identified 2,107 SIDS cases, 96% of whom were diagnosed through autopsy. Ten controls were randomly selected for each case from the same linked birth-death certificate data, matched to the case on year of birth. About 1.4% of mothers of cases and 0.7% of mothers of controls had either placental abruption or placenta previa during the index pregnancy. After adjustment for potential confounders, placental abnormality during pregnancy was associated with a twofold increase in the risk of SIDS in offspring (odds ratio = 2.1, 95% confidence interval 1.3-3.1). The individual effects of placental abruption and placenta previa on the risk of SIDS did not differ significantly. An impaired fetal development due to placental abnormality may predispose an infant to a high risk of SIDS.

Adolescent↗
PubMed1999

Are mono-exponential fits to a few echoes sufficient to determine T2 relaxation for in vivo human brain?

T2 relaxation decay curves from in vivo human brain tissue are rarely mono-exponential. Partial volume averaging further reduces the chance of mono-exponential decay. Moreover, the parameters derived from few-echo mono-exponential fits change with the measurement echo times and have the largest possible variance. In this note, multi-exponential fits to 32-echo relaxation decay curves from in vivo human brain are used to design simulations (where the truth is known) to demonstrate the pitfalls of few-echo mono-exponential interpretations.

Algorithms↗
PubMed1999

Magnetic resonance imaging results of the PRISMS trial: a randomized, double-blind, placebo-controlled study of interferon-beta1a in relapsing-remitting multiple sclerosis. Prevention of Relapses and Disability by Interferon-beta1a Subcutaneously in Multiple Sclerosis.

The PRISMS (Prevention of Relapses and Disability by Interferon-beta1a Subcutaneously in Multiple Sclerosis) trial was a double-blind, randomized, multicenter, phase III, placebo-controlled study of interferon-beta1a in 560 patients from 22 centers in 9 countries with clinically definite or laboratory-supported relapsing-remitting multiple sclerosis. The patients were randomized to receive recombinant interferon-beta1a (Rebif), 22 microg (6 mIU), 44 microg (12 mIU), or placebo, given subcutaneously, three times weekly for 2 years. All patients underwent biannual proton density/T2-weighted magnetic resonance imaging scans to determine the overall magnetic resonance imaging disease activity and burden of disease, and a cohort of 205 patients had 11 initial monthly proton density/T2-weighted and gadolinium-enhanced/T1-weighted magnetic resonance imaging scans. Over the 2 years, the placebo group showed a progressive median increase in burden of disease of 10.9%, whereas the 22-microg group and 44-microg group showed median decreases of 1.2% and 3.8%, respectively. The number of T2 active lesions and percentage of scans showing T2 activity on the biannual scans were also significantly reduced in both treatment groups compared with placebo, with a clear dose-effect favoring the 44-microg dose over the 22-microg dose. In the subgroup undergoing initial monthly scanning, this reduction in activity became statistically significant 2 months after the start of treatment. These results provide strong, objective evidence to support the positive clinical results of reduction in relapses and delay in disease progression. In addition, they also demonstrate a significant dosage effect, favoring the 44-microg dose.

Adult↗
PubMed1999

Changing paternity and the risk of preterm delivery in the subsequent pregnancy.

I studied whether changing a partner, and thus changing the likelihood of human leukocyte antigen (HLA) sharing between mating partners, affects the risk of preterm delivery in the subsequent pregnancy. I identified a total of 128,239 women who had two consecutive births during 1989-1991 through data linkage of the California birth certificates. Paternal date of birth and names on the records of the two consecutive births were compared to determine whether the same father was reported on both records. Three cohorts of women were formed on the basis of the gestational age of their first delivery: <34, 34-36, and >36 weeks. If parental HLA sharing is associated with preterm delivery, the likelihood of HLA sharing was expected to be in a decreasing order from most likely among a <34-week cohort to least likely among a >36-week cohort. Among women in the <34-week cohort, changing partners resulted in a 33% reduction in the risk of early preterm delivery in the subsequent pregnancy compared with those who did not change partners [95% confidence interval (CI), 0.52-0.88]. In contrast, among women in the >36-week cohort, changing partners led to a 16% increase in the risk of early preterm delivery in the subsequent pregnancy (95% CI = 1.04-1.30). Among women in the 34-36-week cohort, changing partners did not affect the risk of preterm delivery (95% CI = 0.78-1.25). These estimates were adjusted for maternal race/ethnicity, age, educational level, prenatal smoking, prenatal care, parity, and interval from birth to conception of the subsequent pregnancy. The findings from this study suggest that the effect of changing paternity depends on the pregnancy outcome with the previous partner and support the hypothesis that parental HLA sharing may be related to preterm delivery.

Adult↗