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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

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

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

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

Maternal history of subfertility and the risk of congenital urinary tract anomalies in offspring.

I studied the relation between a maternal history of subfertility and the risk of congenital urinary tract anomalies (CUTAs) in a case-control study. I defined subfertility as having unprotected intercourse for more than 12 months without getting pregnant at any time before the conception of the index pregnancy. A maternal history of subfertility was associated with a slightly increased risk of CUTAs (adjusted odds ratio (OR) = 1.4, 95% confidence interval (CI) 0.8-2.4). Risk was higher for mothers whose subfertility occurred at 20 years of age or younger (OR = 2.2, 95% CI 1.0-4.9). The effect of a maternal history of subfertility on the risk of CUTAs was exacerbated by maternal smoking during the index pregnancy and by an early onset of smoking history.

Case-Control Studies

A comparison between magnetization transfer ratios and myelin water percentages in normals and multiple sclerosis patients.

Magnetization transfer and T2 relaxation data were obtained for five white and six gray matter brain structures from 10 normal volunteers and 9 multiple sclerosis patients. Thirty MS lesions were also analyzed. Magnetization transfer ratios and myelin water percentages were compared. Both techniques showed a significant difference between the average of white and gray matter of the normal volunteers as well as the average of normal-appearing white matter and gray matter of the multiple sclerosis patients. The average magnetization transfer ratio and myelin water percentage for lesions were significantly lower than those of normal-appearing white matter. Myelin water percentages and magnetization transfer ratios were uncorrelated in white and gray matter but showed a small (R = 0.5, P = 0.005) but significant correlation in multiple sclerosis lesions. In summary, the myelin water percentage and the magnetization transfer ratio provide quantifiable but largely independent measures of multiple sclerosis lesion pathology.

Adult

Unexpected vaginal bleeding and associated gynecologic care in postmenopausal women using hormone replacement therapy: comparison of cyclic versus continuous combined schedules.

OBJECTIVE: To measure gynecologic resources required to care for women who have unexpected vaginal bleeding while using hormone replacement therapy (HRT). DESIGN: A retrospective cohort study based on review of medical records. SETTING: A large health maintenance organization. PATIENT(S): We studied 284 women using continuous combined HRT and 306 women receiving cyclic HRT. MAIN OUTCOME MEASURE(S): We noted episodes of unexpected vaginal bleeding and associated clinic visits and gynecologic procedures recorded during a mean follow-up period of 2 years. RESULT(S): Among women using cyclic HRT for the first time, 38.3% had > or = 1 visit for unexpected bleeding and 12.3% had > or = 1 endometrial biopsy. Among women starting continuous combined HRT, 41.6% had > or = 1 visit for unexpected bleeding and 20.1% had > or = 1 endometrial biopsy. After adjusting for potential confounding variables, we found that recipients of cyclic and continuous combined HRT had similar risks of unexpected bleeding and endometrial biopsy. However, among women continuing HRT for >2 years, those using the continuous combined regimen had somewhat lower rates of unexpected bleeding (22.3 events per 100 patient-years) and endometrial biopsy (10.3 events per 100 patient-years) than those using the cyclic regimen (37.8 episodes of unexpected bleeding per 100 patient-years and 13.9 endometrial biopsies per 100 patient-years). CONCLUSION(S): Unexpected vaginal bleeding and the gynecologic resources required to manage it decreased after 2 years in women using continuous combined HRT but did not decline among those using cyclic HRT.

Aged

Transient neurologic symptoms after spinal anesthesia: an epidemiologic study of 1,863 patients.

BACKGROUND: Recent evidence suggests that transient neurologic symptoms commonly follow lidocaine spinal anesthesia. However, information concerning factors that affect their occurrence is limited. Accordingly, to evaluate many potential risk factors, the authors undertook a prospective, multicenter, epidemiologic study. METHODS: On a voluntary basis, anesthetists at 15 participating centers forwarded a data sheet on patients who had spinal anesthesia to a research nurse blinded to the details of anesthesia and surgery. A subset was randomly selected for follow-up. The pressure [corrected] of transient neurologic symptoms, defined as leg or buttock pain, was the principal outcome variable. Logistic regression was used to control for potential confounders, and adjusted odds ratios and confidence intervals were used to estimate relative risk. RESULTS: During a 14-month period, 1,863 patients were studied, of whom 47% received lidocaine, 40% bupivacaine, and 13% tetracaine. Patients given lidocaine were at higher risk for symptoms compared with those receiving bupivacaine (relative risk, 5.1; 95% CI, 2.5 to 10.2) or tetracaine (relative risk, 3.2; 95% CI, 1.04 to 9.84). For patients who received lidocaine, the relative risk of transient neurologic symptoms was 2.6 (95% CI, 1.5 to 4.5) with the lithotomy position compared with other positions, 3.6 (95% CI, 1.9 to 6.8), for outpatients compared with inpatients, and 1.6 (95% CI, 1 to 2.5) for obese (body mass index >30) compared with nonobese patients. CONCLUSIONS: These results indicate that transient neurologic symptoms commonly follow lidocaine spinal anesthesia but are relatively uncommon with bupivacaine or tetracaine. The data identify lithotomy position and outpatient status as important risk factors in patients who receive lidocaine. Among other factors postulated to increase risk, obesity had an effect of borderline statistical significance, whereas age, sex, history of back pain, needle type, and lidocaine dose and concentration failed to affect risk.

Adult

Penetration kinetics of 5-fluorouracil into pancreatic fluid in post-pancreatoduodenectomy patients.

Our aim was to investigate the pharmacokinetic behavior of 5-fluorouracil (5-FU) in pancreatic fluid and to evaluate its penetration characteristics in post-pancreatoduodenectomy patients. After completing the external drainage of the pancreatic duct during pancreatoduodenectomy surgery, eight patients were administered 1.0 g 5-FU i.v. by a 5 min infusion after the eighth day post-surgery on average. Blood and pancreatic fluid were collected, and the 5-FU concentrations were determined by HPLC assay. Their pharmacokinetic parameters were obtained by PCNONLIN and statistical analysis was performed. The Cmax was 20.03 +/- 18.25 mg/l in pancreatic fluid with a Tmax of 15.6 +/- 9.5 min following i.v. administration and 49.69 +/- 20.75 mg/l in plasma. 5-FU in plasma and pancreatic fluid were all in conformity with a non-linear model with a K(m) of 1098.08 +/- 1426.57 and 11.08 +/- 6.38 mg/l, respectively. The concentrations in pancreatic fluid were similar to that observed in plasma with an average penetration index up to 1.01 +/- 0.49. It is suggested therefore that 5-FU is capable of penetrating from blood into the pancreas as evidenced by the observed pancreatic concentrations.

Body Fluids

Pharmacokinetics of 5-fluorouracil and its penetration into pancreatic juice in dogs.

AIM: To study the pharmacokinetic behavior of 5-fluorouracil (5-FU) in pancreatic juice in dogs and its correlation with 5-FU in plasma, and to evaluate its penetration characteristics. METHODS: After placing a pancreatico-drainage tube, 8 dogs were injected 5-FU 250 mg i.v. Blood and pancreatic samples were collected and the 5-FU concentrations were determined by HPLC. The pharmacokinetic parameters were obtained with statistical analysis. RESULTS: The mean slopes of the terminal phase (K10) in plasma and pancreatic juice were 9.4 h-1 and 10.2 h-1, respectively (P > 0.05). The pharmacokinetic behaviors of 5-FU in plasma and pancreatic juice fitted a nonlinear model. Its penetration index was 3.39 +/- 2.84. The penetration of 5-FU from blood to pancreatic juice was relatively rapid, demonstrating a consistently higher concentration in pancreatic juice than in plasma. CONCLUSIONS: The elimination phase of 5-FU in plasma was similar to that in pancreatic juice, indicating that they were in the same kinetic compartment.

Animals

In vivo measurement of T2 distributions and water contents in normal human brain.

Using a 32-echo imaging pulse sequence, T2 relaxation decay curves were acquired from five white- and six gray-matter brain structures outlined in 12 normal volunteers. The water contents of white and gray matter were 0.71 (0.01) and 0.83 (0.03) g/ml, respectively. All white-matter structures had significantly higher myelin water percentages (signal percentage with T2 between 10 and 50 ms) than all gray-matter structures. The range in geometric mean T2 of the main peak for both white and gray matter was from 70 to 86 ms. T2 distributions from the posterior internal capsules and splenium of the corpus callosum were significantly wider (width is related to water environment inhomogeneity) than those from any other white- or gray-matter structures. Thus, quantitative measurement and analysis of T2 relaxation reveals differences in brain tissue water environments not discernible on conventional MR images. These differences may make short T2 components reliable markers for normal myelin.

Adult

Clinical and magnetic resonance imaging changes correlate in a clinical trial monitoring cyclosporine therapy for multiple sclerosis. The MS Study Group.

Magnetic resonance imaging (MRI) was used to monitor cyclosporine therapy for chronic progressive multiple sclerosis in a multicenter clinical trial and an analysis was performed to determine whether there was a correlation between clinical changes and MRI changes. MRI was performed on 163 patients at the onset and completion of the 2-year study. Burden of disease (BOD, lesion load) was quantitated by a single observer using a computer program. Active lesions were also identified. The Expanded Disability Status Scale (EDSS) score was determined every 3 months MRI data did not show any effect of cyclosporine treatment on BOD progression (mean 24.5% increase/yr) or lesion activity. However, there was a statistically significant positive correlation between the baseline total BOD value and the baseline EDSS score (r = 0.221, p = 0.005) and a positive correlation between the percent changes in BOD from baseline to exit and EDSS score (r = 0.186, p = 0.018). The study supports the concepts that MRI is a useful technique in monitoring therapeutic trials and that MRI is a direct measure of pathology.

Brain

Premenopausal ovariectomy-related bone loss: a randomized, double-blind, one-year trial of conjugated estrogen or medroxyprogesterone acetate.

The purpose of this study was to contrast the effects of conventional estrogen treatment with medroxyprogesterone on cancellous and cortical bone change in the first year following premenopausal ovariectomy. This 1-year double-blind randomized therapy trial was stratified by osteoporosis family history and performed in an academic medical center and community hospitals. Premenopausal women 45 +/- 5 years old, postovariectomy for benign diseases were provided 600 mg/day of calcium and randomized to daily therapy with conjugated equine estrogen (CEE, 0.6 mg) or medroxyprogesterone (MPA, 10 mg). The primary outcome variable was spinal quantitative computed tomography (QCT) bone density change over 1 year with additional outcomes of dual-energy X-ray absorptiometry (DXA) of proximal femur (FN), whole body (WB), and spine segment (WBS) and N-telopeptide, bone-specific alkaline phosphatase, and other bone marker, hormonal, and weight changes. Results in the 33 women completing the study, whose initial bone densities were normal (QCT 133 mg/cm3, femoral neck 0.94 g/cm2, whole body DXA 1.13 g/cm2), showed annual QCT loss during CEE therapy of -11.5 mg/cm3 (p < 0.0007) and MPA bone loss of -19.7 mg/cm3 (p < 0.0001). Losses were marginally greater on MPA than CEE (p = 0.04). Extremely high postovariectomy (5 days) and pretreatment resorption markers (> 3 SD above premenopausal normal levels) were significantly related to bone loss. Across the year, resorption decreased during CEE but increased on MPA treatment. Significant DXA bone losses were prevented by CEE treatment (-1.4% FN, -.4% WB, and -1.5% WBS, all NS). However, DXA bone loss was not prevented by MPA treatment (-5% FN, -2.8% WB, and -6.1% WBS, all p < 0.03). Average weight gain was significant (+ 3.2 +/- 4.0 kg) and greater on CEE than MPA (+ 4.7 vs. + 2.0 kg, p = 0.049). In conclusion, CEE therapy did not prevent significant 8% cancellous spinal bone loss in the first year following premenopausal ovariectomy, despite supplementation with 600 mg/day of calcium, good control of vasomotor symptoms, and nearly 5 kg of gain in weight. Significant DXA bone loss, however, was prevented by CEE, but not by MPA therapy. These unexpected results were statistically related to high bone resorption following ovariectomy, which CEE suppressed but MPA did not. Bone formation markers increased during MPA therapy but were unchanged during CEE therapy.

Absorptiometry, Photon

Ovulatory premenopausal women lose cancellous spinal bone: a five year prospective study.

Healthy premenopausal women with regular cycles are believed to be increasing or maintaining bone density. However, few studies have prospectively documented spinal cancellous bone, the bone that changes rapidly in response to reproductive hormones, in this population. Furthermore, our previous one-year study documented that 24% of the one-year bone change by quantitative computed tomography (QCT) was related to subclinical ovulatory disturbances (short luteal phase and non-ovulation) in the presence of regular menstrual cycles. The purpose of this study was to document the cancellous bone change over five years in this initially ovulatory, premenopausal cohort of 66 healthy women. Thirty-seven women, who continued to be premenopausal and have regular cycles, completed this five-year study. Those enrolled differed only by being older and weighing less than those who could not be contacted (n = 19) or who declined to participate (n = 10). Documentation of current ovulatory characteristics was obtained for at least three cycles in 27 women. At the five-year assessment, the volunteers were 40.6 (range 26-47) years old, weighed 58.5 (41-77) kg, and were 160.9 (149-174) cm in height. All were premenopausal, healthy, nonsmokers with regular menstrual cycles (mean 27.7, range 24-33 days). Six women with intervening events (such as pregnancy or use of oral contraceptives) had interval (12 to 60 months) QCT changes similar to the remaining 31 (-7.98 vs. -4.92 mg/cm, p = 0.1, respectively). Mean five-year QCT was 143.0 +/- 20.2 mg/cm, whereas the initial mean value was 151.9 +/- 20.1 mg/cm. Significant QCT loss over five years (-8.9 +/- 6.2 mg/cm) (95% Cl -6.9 to -11.0) correlated with QCT change in the first year (r = 0.629, p < 0.001). First-year change was not related to the subsequent four-year interval change (r = -0.056, p = 0.74), however. Five-year QCT change was not related to age, weight, osteoporosis family history, estimated calcium intake, or exercise, but did correlate with year one luteal index (luteal/cycle length) (r = 0.339, p = 0.043). Significant cancellous spinal bone loss occurs in healthy, ovulatory premenopausal women, and is influenced by subclinical disturbances of ovulation.

Adult

Thymus in myasthenia gravis: comparison of CT and pathologic findings and clinical outcome after thymectomy.

PURPOSE: To correlate computed tomographic (CT) appearance of the thymus with results from histologic examination of thymic tissue and clinical outcome in patients with generalized myasthenia gravis who underwent thymectomy. MATERIALS AND METHODS: Forty-five patients with myasthenia gravis underwent CT of the thorax and thymectomy. Findings at clinical follow-up were available in all patients. RESULTS: Twenty-six patients had normal CT findings, seven had a diffusely enlarged thymus, and 12 had a focal mass. The results of histologic examination showed that 16 of 26 patients with normal CT findings had normal thymic tissue and 10 had lymphoid follicular hyperplasia; all seven patients with an enlarged thymus had lymphoid hyperplasia. Five of 12 patients with a focal mass at CT had lymphoid hyperplasia, and seven had thymoma. Clinical improvement following thymectomy was observed in 27 (93%) of 29 patients with lymphoid hyperplasia or thymoma and 11 (69%) of 16 patients with normal histologic examination (P < .03, chi(2) test). CONCLUSION: The presence of an enlarged thymus or a focal mass in patients with myasthenia gravis indicates lymphoid hyperplasia or thymoma. However, CT is of limited value in distinguishing lymphoid follicular hyperplasia from a normal thymus or thymoma and in predicting clinical outcome.

Adolescent