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Biomedical subjects

S Wallace

Publications and source records attributed to S Wallace.

At least 37 records · Page 2Linked to original sources
PubMed2001

Recombinant human erythropoietin for chronic renal failure anaemia in pre-dialysis patients.

BACKGROUND: Treatment with recombinant human erythropoietin (rHu EPO) in dialysis patients has been shown to be highly effective in terms of correcting anaemia and improving quality of life. There is debate concerning the benefits of rHu EPO use in pre-dialysis patients. There is a concern that rHu EPO may accelerate the deterioration in renal function, however the opposing view is that if rHu EPO is as effective in pre-dialysis patients that by improving the patients sense of well-being the onset of dialysis could be delayed. OBJECTIVES: To assess the effects of rHu EPO use in pre-dialysis patients with renal anaemia. SEARCH STRATEGY: We searched MEDLINE (1980 to May Week 3 2001), EMBASE (1984 to Week 24 2001), BIOSIS (1985 to January 1997), CINAHL (1982 to October 1997), The Cochrane Library (Issue 1, 1997), CHEMABS (1984 to November 1996), SIGLE (1980 to June 1996), CRIB (10th edition, 1995), UK NRR (14TH consolidation, September 1996), RSC ( 1980 to February 1997), HealthSTAR (1995 to October 1997), IBSS (1984 to July 1997), NEED (July 1997) and reference lists of relevant articles. We contacted biomedical companies and investigators in the field and we hand searched Kidney International (including all supplements but excluding all conference proceedings except for 1994) July 1983 to May 1997 inclusive. The internet was also searched on: August 1997. We had also identified some studies from a previous broad search for all randomised controlled trials (RCTs) relevant to the management of end-stage renal disease. Date of the most recent search: June 2001. SELECTION CRITERIA: RCTs or quasi-RCTs comparing the use of rHu EPO with no rHu EPO or placebo in pre-dialysis patients. DATA COLLECTION AND ANALYSIS: Only published data were used. Data were abstracted by a single investigator onto a standard form. A sample of the data abstracted was double-checked by another reviewer. The data abstracted were relevant to the predetermined outcome measures. Some authors were contacted to clarify how patients were allocated to groups. All authors from included studies were contacted for missing information. MAIN RESULTS: Twelve studies with a total of 232 participants met the inclusion criteria and where possible data from these were summated by meta-analyses (Peto's Odds Ratio (OR) and Weighted Mean Difference (WMD)). The majority of the trials included small numbers and were of short duration (8-10 weeks) with the exception of three trials. There was a marked improvement in haemoglobin (mean difference 2.3g/dL, 95% CI 1.37 to 3.23) and haematocrit (WMD 9.92%, 95% CI 8.78 to 11.05) with the treatment and a decrease in the number of patients requiring blood transfusion (OR 0.25, 95% CI 0.09 to 0.69). The data from all studies which reported quality of life or exercise capacity demonstrated an improvement in the rHu EPO group. None of the measures of progression of renal disease (when a summary statistic was calculated) demonstrated a statistically significant difference. Though the requirement for antihypertensive treatment appears to be increased by rHu EPO (OR 1.84, 95% CI 1.02 to 3.32), there was no other statistically significant increase in adverse events. Based on the limited current evidence, decisions therefore have to be made on whether the putative benefits in terms of quality of life identified in the review are worth the extra costs of pre-dialysis rHu EPO. REVIEWER'S CONCLUSIONS: This review has shown that treatment with rHu EPO in pre-dialysis patients corrects anaemia and avoids the requirement for blood transfusions. There are also improvements in quality of life and exercise capacity. There may be increased hypertension. Most of the trials were not of sufficient duration to assess the effects of rHu EPO on progression of renal disease. In the long term, questions still remain about whether pre-dialysis rHu EPO either speeds up or delays the onset of dialysis. Thus there is insufficient evidence on the total costs and benefits of treating pre-dialysis patients with rHu EPO.

Anemia↗
PubMed2001

Imaging techniques used for the detection of 8-oxoguanine adducts and DNA repair proteins in cells and tissues.

The presence of 8-oxoguanine (8-oxoG) in DNA is considered a marker of oxidative stress and DNA damage. Numerous biochemical techniques have been described for its detection in cells or tissues. Although these approaches are quantitative, they do not provide insights into whether the lesion occurs in mitochrondrial versus genomic DNA. In addition, biochemical techniques are not amenable to the evaluation of individual cells or archival tissues. Antibodies have been raised against 8-oxoG, which may circumvent some of these issues. In this review, we described the use of in situ imaging techniques to detect oxidative DNA damage including the comet assay. We will review our previous work that describes the utility of an antibody fragment (Fab) engineered to recognize 8-oxoG in DNA. Furthermore, we will discuss the analysis of DNA repair enzymes in the assessment of oxidative DNA damage. Finally, advantages and potential concerns associated with immunodetection of 8-oxoG are discussed.

Animals↗
PubMed2001

Gliomatosis cerebri in a 10-year-old girl masquerading as diffuse encephalomyelitis and spinal cord tumour.

Gliomatosis cerebri is the unifying term used when diffuse glial infiltration occurs throughout the cerebral hemispheres. The very few cases reported in children have presented with intractable epilepsy, corticospinal tract deficits, unilateral tremor, headaches, and developmental delay. Antemortem diagnosis is difficult because of the vagueness of the physical, radiological and pathological findings. Adult cases may simulate an acute diffuse encephalomyelitis and show postmortem evidence of a marked swelling of the spinal cord. Apparently benign intracranial hypertension with papilloedema has also been recorded. We report a 10-year-old girl who presented with a history and physical signs suggestive of benign intracranial hypertension. A diffuse encephalomyelopathy occurred, which was complicated by spinal cord swelling, followed by deterioration and death. Gliomatosis cerebri affecting the brain and spinal cord was found at postmortem examination.

Brain Neoplasms↗
PubMed2001

B-lymphotropic viruses in a novel tropical splenic lymphoma.

Peripheral blood from patients with a novel tropical splenic lymphoma, characterized by splenomegaly and circulating naïve CD5-negative villous B lymphocytes, has been screened for evidence of an association with the B-lymphotropic viruses, Epstein--Barr virus (EBV), hepatitis C virus (HCV) and human herpesvirus 8 (HHV8). No increased prevalence of EBV, HCV and HHV8 was demonstrated using serological and molecular techniques, compared with a geographical, age-matched control group. However, lymphoma patients had markedly raised EBV antibody levels without a concomitant increase in the rate of detection of viral genomes in the peripheral blood. This phenomenon also occurred in patients with hyper-reactive malarial splenomegaly, a condition that occurs in the same geographical area and that is clinically indistinguishable from tropical splenic lymphoma, adding further weight to the suggestion that there may be an aetiological association between these two disorders.

Adolescent↗
PubMed2001

Federal prison residential drug treatment reduces substance use and arrests after release.

OBJECTIVE: The effectiveness of federal prison-based residential drug and alcohol treatment programs was evaluated using event history procedures that addressed the problem of selection bias and included a wide range of control variables. METHODS: The sample comprised 760 treatment subjects and 809 comparison subjects. Treatment subjects were from 20 different prisons of medium, low, and minimum security levels. Comparison subjects were drawn from over 30 prisons. RESULTS: The results indicated that individuals who entered and completed in-prison residential treatment were less likely to experience the critical postrelease outcomes of new arrests and substance use during the first 6 months following release. CONCLUSIONS: Without controlling for selection bias, the effects of treatment would most likely have been attenuated. The results have greater generalizability than other studies of prison-based treatment. This study occurred within a multisite context of 20 programs serving both male and female inmates and operating within different security levels and different geographic regions.

Adult↗
PubMed2001

Alternative solutions to the problem of selection bias in an analysis of federal residential drug treatment programs.

In an evaluation of prison-based residential drug treatment programs, the authors use three different regression-based approaches to estimating treatment effects. Two of the approaches, the instrumental variable and the Heckman approach, attempt to minimize selection bias as an explanation for treatment outcomes. Estimates from these approaches are compared with estimates from a regression in which treatment is represented by a dummy variable. The article discusses the advantage of using more than one method to increase confidence in findings when possible selection bias is a concern. Three-year outcome data for 2,315 federal inmates are used in analyses where the authors separately examine criminal recidivism and relapse to drug use for men and women. Statistical tests lead the authors to conclude that treatment reduces criminal recidivism and relapse to drug use. The treatment effect was largest when the inference was based on the Heckman approach, somewhat smaller when based on the instrumental variable approach, and smallest when based on the traditional dummy variable approach. Treatment effects for females were not statistically significant.

Crime↗
PubMed2001

Paracrine interactions of chondrocytes and macrophages in cartilage degradation: articular chondrocytes provide factors that activate macrophage-derived pro-gelatinase B (pro-MMP-9).

Cells of the monocyte/macrophage lineage are involved in the development of inflammatory joint diseases such as rheumatoid arthritis. This disease is characterized by cartilage degradation and synovial membrane inflammation with a progressive loss of joint function. The pathological processes are still not well understood. Therefore it would be interesting to develop a suitable experimental in vitro model system for defined studies of monocyte/macrophage and chondrocyte interactions at the molecular level. For that purpose we cocultured chondrocytes from adult human articular cartilage with human monocytes and macrophages for defined periods of time in agarose without addition of serum. We performed zymographic and western blot analysis of culture medium, completed by quantitative RT-PCR of each chondrocyte, monocyte and macrophage RNA, respectively. The reliability of the newly established coculture systems is confirmed by causing a clear decrease of intact aggrecan in the coculture medium plus concurrent appearance of additional smaller fragments and a reduction of chondrocyte aggrecan and collagen II gene expression in the presence of monocytes. In culture medium from cocultures we detected active forms of the matrix metalloproteinases MMP-1, MMP-3 and MMP-9 accompanied by induction of gene expression of MMP-1, membrane type 1 MMP (MT1-MMP) and tissue inhibitor of metalloproteinase 2 (TIMP-2) in chondrocytes. No gene expression of MMP-9 was detectable in chondrocytes, the enzyme was solely expressed in monocytes and macrophages and was downregulated in the presence of chondrocytes. Our results suggest that MMP-9 protein in coculture medium originated from monocytes and macrophages but activation required chondrocyte-derived factors. Because addition of plasmin, a partial activator of pro-MMP-3 and pro-MMP-1, enhanced the activation of pro-MMP-9 and pro-MMP-1 in cocultures but not in monocultured macrophages, and the presence of MMP-3 inhibitor II prevented pro-MMP-9 activation, we assumed a stepwise activation process of pro-MMP-9 that is dependent on the presence of at least MMP-3 and possibly also MMP-1.

Adult↗
PubMed2001

Postadmission disparities in nursing home stays of whites and minority elderly.

This study examined the type of nursing home stay of white and minority elderly and investigated whether minority differences in nursing home admissions were extended to the type of stay, and if so, what accounted for those differences. African American/white and Latino/white elderly were compared with respect to stays of (1) longer than three months, (2) shorter than three months and discharged alive (recovery), and (3) shorter than three months and deceased (terminal). African American elderly in nursing homes were significantly less likely to have recovery stays than were white elderly. Multivariate analysis revealed that this difference was due to Medicaid coverage. Overall, elderly with Medicaid coverage were more likely to make long-term stays in nursing homes. The findings highlight the importance of Medicaid coverage for short-term recovery nursing home stays. Reductions of benefits or restrictions in eligibility would negatively and disproportionately affect the nursing home stays of elderly African Americans.

Black or African American↗
PubMed2001

Effectiveness of water soluble poly(L-glutamic acid)-camptothecin conjugate against resistant human lung cancer xenografted in nude mice.

A camptothecin (CPT) formulation that can be easily administered, is less toxic, and has greater antitumor effect is needed. In this study, a water-soluble CPT derivative was obtained by direct coupling of CPT to poly(L-glutamic acid) (PG) through the C20(S)-hydroxyl group. CPT was released from the resulting conjugate, PG-CPT, in phosphate-buffered saline with a zero-order kinetics in the initial 50 days. The release rates were 0.623% per day, 1.081% per day, and 1.396% per day at pH 5.3, 7.4, and 9.0, respectively. In vitro, PG-CPT was less potent in inhibiting cell growth than was free CPT in all human tumor cell lines tested. However, PG-CPT showed better antitumor activity and tolerability than did CPT in vivo. When H322 human lung tumor cells were inoculated subcutaneously in nude mice, PG-CPT delayed the growth of these well-established tumors with an absolute growth delay of 32 days when given as 4 doses with 4-day intervals between injections at an equivalent CPT dose of 40 mg/kg. When H322 cells were inoculated intratracheally in nude mice, 5 doses of intravenous injection of PG-CPT at an equivalent CPT dose of 10 mg/kg on days 4, 8, 12, 16, and 20 after inoculation significantly prolonged the median survival of treated mice, averaging 1.8-fold that of untreated mice (p=0.01). Increasing the dose of PG-CPT to an equivalent CPT dose of 40 mg/kg per injection administered in 4 doses on days 4, 8, 12, and 16 prolonged the median survival of treated mice by 4-fold (p=0.0008). Significantly, mice with intratracheally inoculated H322 tumors were resistant to both CPT and cisplatin treatments. These studies demonstrated that PG may be used as an effective solubilizing carrier for CPT and that PG-CPT may have potential application in the treatment of lung cancer.

Animals↗
PubMed2001

Genome scan of idiopathic generalized epilepsy: evidence for major susceptibility gene and modifying genes influencing the seizure type.

Idiopathic generalized epilepsy (IGE) is a common, complex disease with an almost exclusively genetic etiology but with variable phenotypes. Clinically, IGE can be divided into different syndromes. Varying lines of evidence point to the involvement of several interacting genes in the etiology of IGE. We performed a genome scan in 91 families ascertained through a proband with adolescent-onset IGE. The IGEs included juvenile myoclonic epilepsy (JME), juvenile absence epilepsy (JAE), and epilepsy with generalized tonic clonic seizures (EGTCS). Our linkage results support an oligogenic model for IGE, with strong evidence for a locus common to most IGEs on chromosome 18 (lod score 4.4/5.2 multipoint/two-point) and other loci that may influence specific seizure phenotypes for different IGEs: a previously identified locus on chromosome 6 for JME (lod score 2.5/4.2), a locus on chromosome 8 influencing non-JME forms of IGE (lod score 3.8/2.5), and, more tentatively, two newly discovered loci for absence seizures on chromosome 5 (lod scores 3.8/2.8 and 3.4/1.9). Our data also suggest that the genetic classification of different forms of IGE is likely to cut across the clinical classification of these subforms of IGE. We hypothesize that interactions of different combinations of these loci produce the related heterogeneous phenotypes seen in IGE families.

Adolescent↗
PubMed2001

Conjugation with (111)In-DTPA-poly(ethylene glycol) improves imaging of anti-EGF receptor antibody C225.

UNLABELLED: Significant liver uptake often limits the clinical application of radiolabeled antibodies in radioimmunodetection. The purpose of this study was to evaluate the gamma-imaging properties of an antiepidermal growth factor receptor (EGFR) antibody, C225, conjugated with heterofunctional poly(ethylene glycol) (PEG) with 1 terminus of the polymer attached to a radiometal chelator, diethylenetriaminepentaacetic acid (DTPA). METHODS: Two preparations of PEG-modified C225, one with 20% and the other with 60% amine substitution, were labeled with (111)In. The conjugates, (111)In-DTPA-PEG-C225, were injected intravenously into nude mice with EGFR-positive A431 tumors. For comparison, C225 directly labeled with (111)In was also injected. In a competitive study, mice with A431 tumors were pretreated intravenously with 100-fold excess of native C225, followed by an injection of (111)In-DTPA-PEG-C225 30 min or 20 h later. In addition, (111)In-DTPA-PEG-C225 was injected into mice with EGFR-positive MDA-MB-468 tumors and EGFR-negative MDA-MB-435 tumors. Images were acquired at 5 min and at 2, 6, 24, and 48 h after injection of the radiotracers. Regions of interest (ROIs) were drawn on the computer images around the whole body, liver, muscle, and tumor. The counts per pixel in the tumor and normal tissues were calculated. At 48 h, the mice were killed and dissected. Blood, liver, muscle, and tumor samples were removed and the radioactivity of each sample was measured. RESULTS: In A431 tumor xenografts, the tumor uptake of C225 modified with PEG was not significantly different than the uptake of unmodified (111)In-DTPA-C225. Uptake in the liver, however, was reduced by 38%-45%, and the reduction increased with increasing degree of PEG substitution. Tumors of A431 and MDA-MB-468 xenografts were clearly visualized with (111)In-DTPA-PEG-C225, whereas tumors of the MDA-MB-435 xenograft, which expresses low levels of EGFR, were not as readily visible. The tumor-to-blood ratios of (111)In-DTPA-PEG-C225 in A431 and MDA-MB-468 xenografts were about 3 fold higher than in MDA-MB-435 xenografts. Blocking EGFR by pretreatment with native C225 significantly reduced the uptake of (111)In-DTPA-PEG-C225 in the liver. The tumor-to-blood ratios in mice with A431 tumors were decreased 2.5-2.7 fold after pretreatment with a large excess of C225. Similar results were obtained with MDA-MB-468 tumor xenografts. In contrast, the tumor-to-blood ratios in mice with MDA-MB-435 tumor xenografts were not significantly different in C225-pretreated mice than in nonpretreated mice. CONCLUSION: These findings indicate that (111)In-DTPA-PEG-C225 selectively localized to the tumors expressing high levels of EGFR. PEG-modification of C225 significantly reduced its liver uptake, resulting in improved visualization of EGFR-positive tumors. Using PEG as a linker between the monoclonal antibody and metal chelator is a useful strategy to optimize the imaging characteristics of antibody-based scintigraphic agents.

Animals↗
PubMed2001

Cold climate wetlands: design and performance.

Constructed wetlands are gaining widespread use as a simple, low cost means of wastewater treatment. Introduction of constructed wetlands technology into the northern United States has been limited by the ability of conventional wetland systems to operate without freezing during the winter. A design approach using subsurface-flow constructed wetlands covered with an insulating mulch layer has been demonstrated to prevent freezing. However, introduction of a mulch layer will affect oxygen transfer rates, pollutant removal performance, and plant establishment. These factors must be addressed for successful application of constructed wetlands technology in cold climates.

Biodegradation, Environmental↗
PubMed2000

Potentiation of ovarian OCa-1 tumor radioresponse by poly (L-glutamic acid)-paclitaxel conjugate.

PURPOSE: It has been shown that paclitaxel (TXL) can strongly enhance tumor cells' sensitivity to radiation. We examined whether the radiosensitizing effect of paclitaxel can be further enhanced when it is delivered systemically as a polymer-drug conjugate that provides enhanced tumor uptake and prolonged release of TXL in the tumor. METHODS AND MATERIALS: C3Hf/Kam mice bearing 8-mm murine ovarian OCa-1 tumors were treated with i.v.-injected Poly(L-glutamic acid)-paclitaxel (PG-TXL) at an equivalent TXL dose of 80 mg/kg, followed 24 h later by single doses of local radiation ranging from 5 to 15 Gy. To determine how long the radiopotentiation persisted at extended times after PG-TXL administration, mice with OCa-1 tumors were given i.v. PG-TXL and 4, 24, 48, 72, 120, or 168 h later their tumors were irradiated at a dose of 10 Gy. Antitumor activity was determined by delay in tumor growth. Cell cycle distribution was assayed using flow cytometry. Tumor vascular volume was estimated using Tc-99 m-labeled red blood cells. RESULTS: PG-TXL strongly potentiated the radioresponse of the OCa-1 tumor. The enhancement factors ranged from 2.79 to 4.28, depending on radiation dose, when PG-TXL preceded radiation by 24 h. The enhancement factor derived from radiation dose-response curves was as high as 5.13. The radiosensitizing effect of PG-TXL was also dependent on the interval between PG-TXL administration and radiation delivery, with greater enhancement been observed when the interval was decreased. The percentage of G2/M cells was significantly increased to 21.4% 48 h after PG-TXL but declined to a preinjection level of 14.8% 72 h after PG-TXL. PG-TXL only moderately increased the tumor vascular volume by 37% 24 h after PG-TXL administration. CONCLUSION: PG-TXL markedly potentiated response of OCa-1 tumor to radiation. When compared to literature data obtained from the same tumor model used here, PG-TXL exhibited stronger radiosensitization effect than TXL. Although its action is possibly mediated by arrest of cells in G2/M phases of cell cycle and by increased tumor blood supply, PG-TXL may exert its radiopotentiation activity through increased tumor uptake of PG-TXL and sustained release of TXL in the tumor. Our results show that conjugation of TXL to a polymer has the potential to further enhance its radiosensitizing activity and that clinical trials of PG-TXL in combination with radiation is warranted.

Animals↗
PubMed2000

No evidence for a major susceptibility locus for juvenile myoclonic epilepsy on chromosome 15q.

Juvenile myoclonic epilepsy (JME) is a distinct epileptic syndrome with a complex mode of inheritance. Several studies found evidence for a locus involved in JME on chromosome 6 near the HLA region. Recently, Elmslie et al. [1997] reported evidence of linkage in JME to chromosome 15q14 assuming a recessive mode of inheritance with 50% penetrance and 65% linked families. The area on chromosome 15q14 encompasses the location of the gene for the alpha-7 subunit of the nicotinic acetylcholine receptor. This could fit the hypothesis that there are two interacting loci, one on chromosome 6 and on chromosome 15 or that there is genetic heterogeneity in JME. In an independent dataset of JME families, we tested for linkage to chromosome 15 but found little evidence for linkage. Moreover, families with more than one family member affected with JME provide a lodscore of 3.4 for the HLA-DR/DQ haplotype on chromosome 6. The lodscore for these same families on chromosome 15q14 is <-2 assuming homogeneity and the maximum lodscore is 0.2 assuming alpha =.25. Only one of these families has a negative lodscore on chromosome 6 and a positive lodscore of 0.5 on chromosome 15q14. Our results indicate that this possible gene on chromosome 15 plays at most a minor role in our JME families. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:49-52, 2000.

Chromosome Mapping↗
PubMed2000

Evidence-based medicine and health economics: a case study of end stage renal disease.

This paper explores the potential for use of an economic evaluation framework alongside systematic reviews. Clinical issues in dialysis therapy for end stage renal disease are used as case studies. The effectiveness data required were obtained from a systematic review of randomized controlled trials. Resource use and cost data were obtained from three sources; the identified randomized controlled trials, a separate review of observational studies and primary data collection. The results of the case studies show that, although simple economic evaluations were possible, issues arose, such as how transferable results are between settings and how appropriate it is to focus on the average patient. The interface between economic evaluation and systematic reviews needs to be further developed in order to ensure that the best available evidence can be used to inform future policy and research.

Chi-Square Distribution↗
PubMed2000

Biodistribution of paclitaxel and poly(L-glutamic acid)-paclitaxel conjugate in mice with ovarian OCa-1 tumor.

PURPOSE: Poly(L-glutamic acid)-paclitaxel (PG-TXL) is a water-soluble paclitaxel (TXL) conjugate made by conjugating TXL to poly(L-glutamic acid) via ester bonds. In preclinical studies, PG-TXL has shown significant antitumor activity against a variety of solid tumors. To elucidate the relationship between tissue distribution and antitumor efficacy of PG-TXL, we studied and compared the biodistribution of PG-TXL and TXL. METHODS: Female C3Hf/Kam mice bearing syngeneic ovarian OCa-1 tumors were injected with either [3H]TXL or PG-[3H]TXL at an equivalent TXL dose of 20 mg/kg. Mice were killed at various times after drug injection, and samples of blood, spleen, liver, kidney, lung, heart, muscle, brain, fat, and tumor were removed and the radioactivity counted. In addition, concentrations of free [3H]TXL released from PG-[3H]TXL in the spleen, liver, kidney, and tumor were analyzed by using high-performance liquid chromatography (HPLC). Whole-body autoradiographs of mice killed 1 day and 6 days after administration of PG-[3H]TXL were obtained to study the intratumoral distribution of PG-TXL. RESULTS: When [3H]TXL was conjugated to polymer, the biodistribution pattern of PG-[3H]TXL differed from that of [3H]TXL. Based on area under the tissue concentration-time curve (AUC) values, tumor exposure to [3H]TXL was five times greater when administered as PG-TXL than as TXL formulated in Cremophor EL/alcohol vehicle. Furthermore, concentrations of free paclitaxel released from PG-[3H]TXL remained relatively constant in tumor tissue, being 489, 949 and 552 ng/g tumor tissue at 5, 48 and 144 h after dosing, respectively. Autoradiographic images of mice injected with PG-[3H]TXL revealed that radioactivity was primarily located in the periphery of the tumor on day 1 after drug administration and was homogeneously diffused into the center of the tumor by day 6. Over the 144-h study period, [3H]TXL concentrations, predominantly as the inactive conjugate, were higher in tissues with a more abundant reticular endothelial system (i.e. liver, kidney, spleen, lung) than in tissues with less abundant or lacking RE systems (i.e. muscle, fat, brain). Both [3H]TXL and PG-[3H]TXL were excreted primarily through the hepatobiliary route, with a small fraction of each drug (5% and 8.7%, respectively) excreted into the urine within 48 h. CONCLUSIONS: This study indicates that the distribution to tumor tissue was enhanced when [3H]TXL was administered as a macromolecular conjugate, and that free TXL was released and maintained within the tumor for a prolonged period. Thus, the antitumor activity of PG-TXL observed in preclinical studies may be attributed in part to enhanced tumor uptake of PG-TXL.

Animals↗
PubMed2000

Dosimetry errors in endovascular high-dose-rate brachytherapy.

Monte Carlo data were used to demonstrate the dosimetry of the microSelectron high-dose-rate (HDR) iridium 192 (192Ir) stepping source. These data were used to assess the accuracy of the Nucletron brachytherapy planning system (BPS version 13) for peripheral vessel endovascular brachytherapy. Dose rates from the high-dose-rate (HDR) source are calculated using the Monte Carlo code MCNP4A. Calculations are made at 0.25-cm intervals in the longitudinal direction on sleeves of radii of 1 and 0.25 cm. The Monte Carlo data are summed and weighted to simulate the longitudinal dose distribution at a distance of 1 and 0.25 cm from an 192Ir source stepping through a straight pathway. A comparison is made between the simulated Monte Carlo dosimetry and the Nucletron brachytherapy planning system's dosimetry. This study illustrates and quantifies the dosimetric errors at small distances associated with a point source dose calculation algorithm. The effects of step size, dwell time optimization, and active length on the accuracy of BPS v.13 for HDR endovascular brachytherapy are demonstrated.

Algorithms↗