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Biomedical subjects

R Wong

Publications and source records attributed to R Wong.

At least 73 records · Page 4Linked to original sources
PubMed1999

Treatment of early epithelial ovarian cancer with chemotherapy and abdominopelvic radiotherapy: results of a prospective treatment protocol.

PURPOSE: To test the hypothesis that the combination of adjuvant chemotherapy and abdominopelvic radiation (APRT) improves the outcome of patients with early ovarian cancer compared to treatment with APRT alone. METHODS AND MATERIALS: Between 1991 and 1994, 93 patients with Stage I to III, optimally cytoreduced, invasive, epithelial ovarian cancer were treated with sequential chemotherapy and APRT. Treatment was assigned using a prognostic classification that was derived from previous cohorts of patients. Low-risk patients (n = 9) received APRT alone, intermediate-risk patients (n = 66) received two courses of cisplatin followed by APRT, and high-risk patients (n = 18) received 6 courses of cisplatin and cyclophosphamide followed by APRT. RESULTS: Disease recurred in 22 patients, and was confined to the pelvis or abdomen in 15. Nine patients died and the remainder were alive with disease after receiving salvage chemotherapy. The 3-year disease-free and overall survivals were 78% and 91%, respectively. The prognostic classification used to assign treatment was the only factor that predicted disease-free survival (83% and 59% at 3 years for low/intermediate- and high-risk patients, respectively; p = 0.03). There was no detectable difference in outcome between the present series and an historical control group treated with APRT alone. Treatment was well tolerated and only 2 patients (2.5%) developed serious complications. CONCLUSION: APRT is an effective adjuvant treatment for carefully selected patients with early ovarian cancer. The addition of chemotherapy as used in this study to APRT does not significantly improve outcome compared to APRT alone.

Adult↗
PubMed1999

Busulphan level and early mortality in thalassaemia patients after BMT.

The aim of the study was to correlate busulphan (BU) levels of thalassaemia patients with outcome of allogeneic transplant. BU levels were measured by gas chromatography mass fragmentography. All patients received a standardised dose of BU 16 mg/kg, and cyclophosphamide 150 or 200 mg/kg. For area-under-the-curve analysis (AUC), blood samples were obtained at 0, 1, 2, 3, 4 and 6 h after the first and fifth dose for all patients, and additional levels were measured after ninth and/or 13th dose in most patients. Outcome parameters examined included veno-occlusive disease of liver (VOD), idiopathic interstitial pneumonitis, chimerism, and day 90 survival. Twenty consecutive thalassaemia patients who underwent haematopoietic stem cell transplantation were studied. The median age at transplant was 11.2 years (range 3-21 years). Mean BU AUC levels were correlated with age at transplant (r = 0.58, P = 0.007). Nine patients developed VOD and six had mixed chimerism, but these did not correlate with mean BU AUC level. Four patients died before day 50 from VOD and interstitial pneumonitis. Patients with BU AUC levels greater than the median (908 micromol x min/l) had significantly lower probability of survival at day 90 (60%), whereas patients with BU AUC level less than the median all survived beyond day 90. No patient had graft rejection. In conclusion, a high BU AUC level was associated with a higher treatment-related mortality in thalassaemia patients after transplant.

Adolescent↗
PubMed1999

Financial assistance from middle-aged couples to parents and children: racial-ethnic differences.

OBJECTIVES: To examine racial-ethnic differences in the allocation of financial transfers to parents, children, and others by middle-aged couples. METHODS: Multinomial specification of alternative recipients of financial transfers, using data from the 1992 Health and Retirement Survey. RESULTS: Transfer patterns are sensitive to parental health and wealth, to children being young or in school, as well as to the donors' health and wealth. Controlling for these and other factors, including family size and structure, Blacks and Whites are the most likely, and Hispanics the least likely, to financially help their parents compared to assisting offspring. Black couples are the most likely to sacrifice their own consumption to assist parents financially. DISCUSSION: Future research on transfers should attempt to capture unmeasured noneconomic sources of variation proxied by the race-ethnicity indicator.

Aged↗
PubMed1999

Incidence of contamination of preserved saline solutions during normal use.

PURPOSE: To ascertain the incidence of microbial contamination of preserved contact lens saline solutions with normal patient use. METHODS: Eight different brands of preserved saline were dispensed to 40 patients attending optometric practices in the Sydney area. After specific periods of time (7 to 28 days), the samples were collected and the solution bottle nozzles and contents underwent microbial analysis. RESULTS: The overall contamination rate was approximately 26% for contents only and 55% for nozzles of preserved saline solutions. This rate remained constant for all periods of use. Coagulase-negative Staphylococci were most frequently isolated. No Acanthamoebae were isolated. Saline preserved with ethylene-diamine-tetraacetic acid (EDTA) in conjunction with sorbic acid showed the highest percentage of sterility. CONCLUSIONS: The results of this study show that preserved saline became contaminated with gram-positive bacteria. This is in contrast to our previously published paper using unpreserved saline, where contamination was predominantly with gram-negative bacteria. The overall contamination rates with preserved saline were lower than for unpreserved saline.

Contact Lens Solutions↗
PubMed1999

Pathomorphometrical characteristics of atherosclerosis in youth. A multinational investigation of WHO/World Heart Federation (1986-1996), using atherometric system.

BACKGROUND AND AIM: From 1986 to 1996, 1339 autopsies were performed on children and young adults, aged 5-34 years, in 18 countries of five continents in the course of the multinational investigation of the World Health Organization/International Society and Federation Cardiology (WHO/ISFC), "Pathobiological Determinants of Atherosclerosis in Youth" (PBDAY). A set of 966 left-half thoracic and 947 left-half abdominal aortae and 958 right coronary arteries were processed in the Center of Investigations and References of Atherosclerosis of Havana (CIRAH), i.e., one of the Reference Centers of the PBDAY. Pathomorphological and morphometrical analyses were carried out by a well-established method, the Atherometric System (AS). METHODS AND RESULTS: By qualitative analysis AS permitted the identification of each type of atherosclerotic lesions (AL). The quantitative analysis, using a digitizer (MYPAC-Japan, a PC-Pentium 200 Mhz-32 MB RAM), and the software Atherosoft, allowed the measurement of the intima surface occupied by any kind of AL, and estimation of the volume occupied and thus the degree of obstruction and stenosis of the lumen. The autopsy data were divided into three age groups: a) 5 to 14 years; b) 15 to 24 years and c) 25 to 34 and processed by age and sex. The commercial package NCSS was utilized for statistical analysis of the data. CONCLUSIONS: Of particular interest were the following findings: a) Atherosclerosis increases with age; b) Fatty streaks (FS) were always present already at 5 years of age, independent of the country, climate, state of nourishment, type and amount of foods and the habits and lifestyle of the population studied. FS progressed most rapidly from 15 to 24 years. The fibrous plaque began to appear slowly at the end of the second and rapidly progressed after the third decades. The severe plaque was rarely observed before 30 years of age; it appeared in the fourth decade and then progressed slowly, but steadily.

Adolescent↗
PubMed1998

Interstitial fluid pressure in cervical carcinoma: within tumor heterogeneity, and relation to oxygen tension.

BACKGROUND: Interstitial fluid pressure (IFP) is elevated in many animal and human tumors. The authors assessed tumor IFP and its relation to tumor oxygenation in a prospective clinical study of patients with cervical carcinoma. METHODS: Measurements were made in 77 patients with cervical carcinoma prior to treatment. IFP was measured in normal paravaginal submucosal tissue and at one to five positions in the visible tumor with the patients anesthetized and in the lithotomy position. Tumor oxygen tension was measured immediately prior to IFP using a polarographic needle electrode. Patients were treated with radiotherapy only. Response was evaluated 3 months after the completion of radiotherapy. RESULTS: There was substantial variation in IFP from region to region in some tumors. The mean IFP in individual tumors ranged from 3 to 48 millimeters of mercury (mmHg). The overall mean and median values for the entire patient group were 19 mmHg and 17 mmHg, respectively. IFP was significantly higher in tumor tissue than in normal tissue (P < 0.0001). Tumors with high IFP were more likely to be hypoxic (P < 0.007) and less likely to regress completely with radiotherapy (P < 0.04). CONCLUSIONS: IFP in cervical carcinoma is elevated above normal tissue values. Multiple measurements are needed to evaluate IFP in these tumors. High IFP is associated with hypoxia and may provide information about the mechanism of hypoxia on which treatment can be based.

Adult↗
PubMed1998

Pharmacokinetics of oral ganciclovir alone and in combination with zidovudine, didanosine, and probenecid in HIV-infected subjects.

The aim of this study was to determine whether oral ganciclovir interacted pharmacokinetically with zidovudine (AZT), didanosine (ddI), or probenecid. A multicenter, open-label, randomized, crossover pharmacokinetic study with four phases was undertaken at an outpatient private research center and at university research clinics. Twenty-six HIV-infected adults (23 men, 3 women) with cytomegalovirus (CMV) seropositivity and CD4+ T-lymphocyte count > or =100 cells/microl were studied. Patients had to be stable on antiretroviral therapy for at least 4 weeks. Patients with a history of opportunistic infection or gastrointestinal symptoms were excluded. Measurements included serial blood and urine samples during the dosing intervals at steady state. The steady-state pharmacokinetics of ganciclovir were determined after the participants had stabilized and were tolerating AZT or ddI therapy. When a 1000-mg dose of oral ganciclovir was taken every 8 hours, there was a significant mean increase in Cmax and dosing interval area under the serum concentration time curve over a dosing interval (AUC) for the two antiretroviral drugs: for AZT, 61.6% and 19.5%, respectively; for ddI when administered sequentially (2 hours before ganciclovir), 116.0% and 114.6%; and for ddI administered simultaneously with ganciclovir, 107.9% and 107.1%, respectively. There was no significant change in renal clearance for either antiretroviral drug, suggesting that the interaction did not occur through a renal mechanism. There was no significant change in mean ganciclovir Cmax and AUC(0-8) when coadministered with AZT. Mean increases in Cmax and AUC(0-8) of oral ganciclovir averaged 40.1% and 52.5%, respectively, when coadministered with probenecid, but decreased by 22.1% and 22.7%, respectively, when oral ganciclovir was administered 2 hours after ddI. There was no change in the mean ganciclovir Cmax or AUC(0-8) when administered simultaneously with ddI. The mean renal clearance of oral ganciclovir was not affected by AZT or ddI coadministration intake, but there was a mean decrease of 19% when coadministered with probenecid. We conclude the increased serum concentration and reduced renal clearance of ganciclovir suggests competition with probenecid for secretion at the renal tubule. The mechanism of the interaction of oral ganciclovir with either AZT or ddI remains to be determined. The magnitude of the effect of oral ganciclovir on ddI pharmacokinetics may result in an increase in ddI concentration-related toxicities. Similarly, the small but significant decrease in ganciclovir concentration with sequential combination ddl therapy may impair the efficacy of oral ganciclovir. For HIV-infected patients receiving ganciclovir and ddI, clinicians should recommend administering the two drugs simultaneously, and patients should be monitored closely for ddI-associated toxicities.

Administration, Oral↗
PubMed1998

In search of a dose-response relationship with radiotherapy in the management of recurrent rectal carcinoma in the pelvis: a systematic review.

PURPOSE: A systematic review of the literature was undertaken to address the question: "What is the most effective dose fractionation schedule for the relief of symptoms in patients with pelvic recurrence from rectal or colorectal carcinoma?" METHODS AND MATERIALS: Cancerlit/Medline-computerized databases were searched between the years 1966-1996. Studies that explored the response to radiotherapy in patients with pelvic recurrence from rectal/rectosigmoid carcinoma were included. Factors that may contribute to differences in results were postulated in advance and the variations encountered between articles were presented. Articles with data applicable to recurrent disease only were included in the primary analysis. The effect of including articles that reported outcomes of recurrences with unresectable primaries and residual disease was presented as a sensitivity analysis. RESULTS: Only retrospective series (level V evidence) were available. The many sources of potential bias inherent in retrospective analyses make the data suitable for hypothesis generation only. Comparison of response was made between "lower" vs. "higher" doses, using 45-50 Gy as the dividing dose, base on the primary analysis. There were no significant differences observable in terms of initial response and the proportion maintaining a response at 6 months, within the range of doses employed. When data from articles that reported outcomes of recurrent disease with primary untreated cancers and postoperative residual disease were included, there was a suggestion for a more favorable response with higher doses. This requires cautious interpretation within the methodological limitations of the data. CONCLUSION: The optimal dose fractionation schedule for the palliation of pelvic recurrence from rectal carcinoma remains undefined. Well-designed randomized studies, with study arms that are sufficiently diverse biologically to allow the detection of a dose-response relationship if one existed, equipped with suitable symptom control end points, are necessary to provide a clinically relevant answer.

Dose-Response Relationship, Radiation↗
PubMed1998

Plasma cytomegalovirus (CMV) DNA load predicts CMV disease and survival in AIDS patients.

In this study, baseline plasma from 619 persons with acquired immunodeficiency syndrome (AIDS) (median CD4+ lymphocyte count -21/microl) who participated in a trial to determine the efficacy of oral ganciclovir for cytomegalovirus (CMV) disease prevention were evaluated for CMV DNA load by qualitative and quantitative polymerase chain reaction (PCR), and correlated with the development of CMV disease and survival. For participants without detectable plasma CMV DNA, the 12-mo Kaplan-Meier CMV disease event rate was 14% and 1% for the placebo and ganciclovir groups, respectively (P < 0.001). For PCR positive participants, CMV disease developed in 43% of placebo and 26% ganciclovir recipients (P < 0.017). Among placebo recipients, CMV PCR positivity was associated with a 3.4-fold increased risk of developing CMV disease (P < 0.001) whereas CD4+ lymphocyte count was not a useful predictor (P = 0.47). A positive plasma CMV DNA PCR was also associated with a 2.5-fold increased risk of death. Each log10 increase in baseline CMV DNA load was associated with a 3.1-fold increase in CMV disease (P < 0.001) and a 2.2-fold increase in mortality (P < 0.001). These data indicate that the risk of developing CMV disease and death in persons with advanced AIDS is directly related to the quantity of CMV DNA in plasma, and is a better predictor than CD4+ lymphocyte count in this population.

AIDS-Related Opportunistic Infections↗
PubMed1998

Oxygenation predicts radiation response and survival in patients with cervix cancer.

BACKGROUND AND PURPOSE: Hypoxia appears to be an important factor in predicting tumor relapse following radiation therapy. This study measured oxygenation prior to treatment in patients with cervix cancer using a polarographic oxygen electrode to determine if oxygenation was an important prognostic factor with regard to tumor control and survival. MATERIALS AND METHODS: Between May 1994 and June 1997, 74 eligible patients with cervix cancer were entered into an ongoing prospective study of tumor oxygenation prior to primary radiation therapy. All patients were evaluated with an Eppendorf oxygen electrode during examination under anesthesia. Oxygenation data are presented as the hypoxic proportion, defined as the percentage of pO2 readings of <5 mm Hg (abbreviated as HP5). RESULTS: The HP5 ranged from 2 to 99% with a median of 52%. With a median follow-up of 1.2 years, the disease-free survival (DFS) rate was 69% for patients with HP5 of < or =50% compared with 34% for those with HP5 of >50% (log-rank P = 0.02). Tumor size above and below the median of 5 cm was also significantly related to DFS (P = 0.0003) and patients with bulky hypoxic tumors had a significantly lower DFS (12% at 2 years) than either bulky oxygenated or non-bulky oxygenated or hypoxic tumors (65%, P = 0.0001). CONCLUSIONS: Hypoxia and tumor size are significant adverse prognostic factors in a univariate analysis of disease-free survival in patients with cervix cancer. A high risk group of patients with bulky hypoxic tumors have a significantly higher probability of relapse and death.

Adenocarcinoma↗
PubMed1998

Thyroid hormone receptor is a negative regulator in p53-mediated signaling pathways.

Thyroid hormone nuclear receptors (TRs) are ligand-dependent transcription factors which regulate growth, differentiation, and development. The molecular mechanism by which TRs mediated these effects remains unclear. A prevailing hypothesis is that TRs exert their biological effects by cooperating with other transcription factors. We have recently shown that the human TR subtype beta1 (hTRbeta1) interacts with the tumor suppressor p53, which plays a critical role in cell-cycle regulation and tumorigenesis. This interaction of hTRbeta1 with p53 leads to an impairment of TR function. The present study examined whether hTRbeta1 could modulate the function of p53. Mapping of the domains of p53 responsible for the interaction with hTRbeta1 indicated that the regions involved resided in the DNA-binding domain and carboxy terminus of p53. In agreement with this finding, hTRbeta1 increased the binding of p53 to p53 DNA-binding elements. This increase in DNA binding, however, resulted in repression of p53-dependent transcription activation in transfected cells. Furthermore, hTRbeta1 led to an inhibition of the p53-mediated induction of bax and gadd45 expression. In contrast, the p53-induced expression of p21 was not affected by hTRbeta1, suggesting that the expression of p53-regulated genes is differentially modulated by hTRbeta1. Because the expressions of bax, gadd45, and p21 are directly regulated by p53, these results indicate that hTRbeta1 can modulate p53-regulated gene expression and support the hypothesis that there is cross-talk between these two regulatory pathways. The cross-talk between these two transcription factors could play an important role in the biology of normal and cancer cells.

Breast Neoplasms↗
PubMed1998

Cardiovascular effects of ozone exposure in human volunteers.

We hypothesized that ozone (O3) exposure acutely affects cardiovascular hemodynamics in humans and, in particular, in subjects with essential hypertension. We studied 10 nonmedicated hypertensive and six healthy male adults. Each subject, after catheterization of the right heart and a radial artery, was exposed in an environmentally controlled chamber to filtered air (FA) on one day and to 0.3 ppm O3 on the following day for 3 h with intermittent exercise. Relative to FA exposure, O3 exposure induced no statistically significant changes in cardiac index, ventricular performance, pulmonary artery pressure, pulmonary and systemic vascular resistances, ECG, serum cardiac enzymes, plasma catecholamines and atrial natriuretic factor, and SaO2. The overall results did not indicate major acute cardiovascular effects of O3 in either the hypertensive or the control subjects. However, mean preexposure to postexposure changes were significantly (p < 0.02) larger with O3 than with FA for rate-pressure product (1,353 beats/min/mm Hg) and for heart rate (8 beats/min); these responses were not significantly different between the hypertensive and the control subjects. Significant O3 effects were also observed for mean FEV1 (-6%), and AaPO2 (> 10 mm Hg increase), which were not significantly different between the two groups. These results suggest that O3 exposure can increase myocardial work and impair pulmonary gas exchange to a degree that might be clinically important in persons with significant preexisting cardiovascular impairment, with or without concomitant lung disease.

Adult↗
PubMed1998

Steady-state relative bioavailability of three oral ganciclovir dosage regimens delivering 6,000 mg/day in patients with human immunodeficiency virus.

This study was designed to determine the steady-state relative bioavailability of ganciclovir after three dosage regimens designed to deliver 6,000 mg/day. The study design was an open-label, randomized, three-treatment crossover design in which 22 human immunodeficiency virus (HIV) and cytomegalovirus (CMV) seropositive patients received in random order multiple oral doses of ganciclovir 1,000 mg six times a day, 1,500 mg four times a day, and 2,000 mg three times a day. Blood samples were obtained on day 3 of each oral regimen over a 24-hour time interval. Mean steady-state average serum concentrations of ganciclovir were greater than 1.0 microgram/mL, which exceeds the median in vitro inhibitory concentration (IC50) of most CMV isolates (0.5-1.0 microgram/mL). All three regimens resulted in values for area under the concentration-time curve from 0 to 24 hours (AUC0-24) that were comparable to those seen after maintenance ganciclovir intravenous infusions of 5 mg/kg/day. The 1,000 mg six times daily regimen resulted in an AUC0-24 that was significantly higher than that of the 1,500 mg four times daily or the 2,000 mg three times daily regimens, although the differences were less than 12.5%.

Administration, Oral↗
PubMed1998

A placebo-controlled trial of the immune modulator, lentinan, in HIV-positive patients: a phase I/II trial.

Lentinan is a beta 1-->3 glucan isolated from Lentinus edodes (Shiitake mushroom) which has immune modulating properties. We have conducted two phase I/II placebo-controlled trials on a total of 98 patients. In one study at the San Francisco General Hospital (SFGH), ten patients each were administered 2, 5, or 10 mg of lentinan or placebo i.v. once a week for eight weeks. In the second study at the Community Research Initiative in New York (CRI), two groups of 20 patients each were administered 1 or 5 mg of lentinan i.v. twice a week for 12 weeks, and ten patients were administered placebo (vehicle containing mannitol plus dextran 40) i.v. twice a week. Entry criteria were an HIV positive test, CD4 levels of 200-500 cells, age 18-60 years, and without current opportunistic infections. This study confirms, in Caucasian subjects also, the good tolerability of lentinan observed in Japanese cancer patients. Side effects were mainly mild, especially when infusion was carried out over a 30-minute period. In the SFGH study, where administration was over a ten minute period, there were nine side effects severe enough to be reported to the FDA (one case each of anaphylactoid reaction, back pain, leg pain, depression, rigor, fever, chills, granulocytopenia and elevated liver enzymes) and there were four patients who discontinued therapy because of side effects. In the CRI study, where infusion was over a 30-minute period, there were no side effects reportable to the FDA and there were four dropouts due to side effects or personal preference. Most side effects resolved promptly after the discontinuation of medication, and all of them were relieved within 24 hours. Patients in the study have shown a trend toward increases in CD4 cells and in some patients neutrophil activity. Because of the small numbers, these values do not have statistical significance. Inasmuch as no side effects such as anemia, leukopenia, pancreatitis or neuropathy were seen, and in view of the positive effects of lentinan on certain surrogate markers (recognizing that these were small studies), we recommended a long-term clinical trial of lentinan in combination with didanosine (ddI) or zidovudine in HIV positive patients. Most patients in these trials did not have measurable p24 levels. In the CRI trials of ten patients with elevated p24 levels, eight on lentinan and two on placebo had decreased p24 levels. Of these decreases, those with lentinan and one with placebo were marked. These results were provocative and needed confirmation. Subsequent to this study, a trial of lentinan in combination with didanosine (ddI) showed a mean increase of 142 CD4 cells/mm3 over a twelve month period, in contrast to a decrease in CD4 cells in patients on ddI alone (Gordon et al. 1995).

Adjuvants, Immunologic↗
PubMed1998

Absolute bioavailability and dose proportionality of oral ganciclovir after ascending multiple doses in human immunodeficiency virus (HIV)-positive patients.

This study was designed to determine the bioavailability and dose linearity and proportionality of ganciclovir after multiple oral administrations of 3,000 mg to 6,000 mg per day. In an open-label, randomized, four-treatment crossover design, 24 patients seropositive for human immunodeficiency virus (HIV) and cytomegalovirus (CMV) received in random order multiple oral doses of ganciclovir 1,000 mg every 3 hours (six times a day), 1,000 mg four times a day, and 1,000 mg three times a day and a single 5-mg/kg intravenous infusion (over 1 hour) of ganciclovir. Blood samples for pharmacokinetic determinations were obtained on day 3 of each oral regimen and on the day of the intravenous infusion over a 24-hour time interval. Mean steady-state average serum concentrations of ganciclovir were 0.54, 0.79, and 0.99 microgram/mL, respectively, with the 3, 4, and 6 g/day oral regimens. The steady-state area under the concentration-time curve (AUC0-24) for the 6,000 mg/day oral regimen approached that of the single-dose intravenous regimen. There was a proportional increase in AUC0-24 between the 3 and 4 g/day dosage regimens, but not between the 4 and 6 g/day regimens. This suggests nonlinear absorption of ganciclovir at higher dosages, although the departure from proportionality was less than 11%.

Adult↗
PubMed1998

Atherosclerotic lesions, myocardial damage and lipidograms: a multiarterial study applying an atherometric system and canonical correlation.

472 autopsy subjects were examined with the following aims: to study the association pattern of atherosclerotic lesions between different arterial sectors, the impact of serum lipid disorders (total cholesterol, HDL-c, LDL-c, VLDL-c, and triglycerides were analyzed) and the association pattern between the atherosclerotic lesions in different arterial sectors and the degree of heart damage. For morphometric analysis of the vessels (aorta, circle of Willis, coronary, renal, iliac, and femoral arteris) the atherometric system was used. The most relevant results were as follows: the lipid disorders show their greatest impact in the heart, coronary and femoral arteries and abdominal aorta, whereas the strongest correlations between the atherosclerotic lesions in different arterial sectors were found in those with anatomical continuity.

Arteries↗
PubMed1998

Routine analysis of plasma busulfan by gas chromatography-mass fragmentography.

Busulfan (BU) is a widely used alkylating agent for antineoplastic therapy and marrow ablation in preparation for bone marrow transplantation (BMT). High-dose BU often leads to successful preparation and low relapse but is associated with veno-occlusive disease of liver. We established a protocol to determine postdosage plasma BU concentrations by gas chromatography-mass fragmentography in an attempt to relate clinical outcome to plasma BU concentrations. We used nonisotopic pusulfan as the internal standard. After extraction into ethyl acetate, BU and pusulfan were iodinated into 1, 4-diiodobutane and 1,5-diiodopentane, respectively. Gas chromatography-mass spectrometry (GC-MS) analysis was carried out on an Hewlett-Packard (HP) 5890II gas chromatograph with a 30-m 100% methyl silicon narrow bore, fused-silica capillary column interfaced with an HP 5970A mass spectrometer. Helium was the carrier gas. The sample molecules were identified by total ion monitoring and quantified by selective ion monitoring of m/z 183 and 197. The calibration curve was linear to 4 mg/L. The limit of quantification was 0.04 mg/L, and the analytical recovery was approximately 97%. The within-day and between-day imprecision (CV) was <6% and 9%, respectively. In a preliminary study of 12 children, the BU areas under the BU-time curve were 616-949 micromol. min/L after the first dose and 793-1143 micromol. min/L after the fifth dose. We conclude that the GC-MS procedure is suitable for routine analysis of plasma BU.

Adolescent↗