Determining the prevalence and risk factors for prescription drug unaffordability.

BACKGROUND: Prescription affordability is a key component of healthcare accessibility and a determinant of health outcomes. Prior studies indicate that up to 1 in 4 Americans report difficulty affording prescriptions. OBJECTIVE(S): This study aims to identify factors associated with cost-based prescription refusal. METHODS: We identified 17,869 study participants from the 2017 National Health Interview Survey who had been prescribed at least one medication in the past 12 months. The outcome was defined as inability to afford at least one prescription medication. Covariates included demographic data, medical history, and social attitudes. Logistic regression models were constructed to identify predictors of cost-based prescription refusal. RESULTS: Among 8223 study participants, 8.1% reported the inability to afford at least one prescription medication in the past 12 months. Twenty-seven covariates were correlated with prescription unaffordability, and 8 were selected by the LASSO: Income (Odds ratio (OR) 0.55), Concerned About Bills (OR 2.0), Emergency Department Visits past 12 months (OR 1.33), Dissatisfaction with Medical Care (OR 1.3), Seeking Insurance Through the Health Insurance Marketplace (OR 1.26), Feeling Sad Most of the Time (OR 1.24), History of Asthma (OR 1.26) and History of Diabetes (OR 1.24). CONCLUSIONS: Prescription unaffordability remains a significant public health problem and is more common among low-income individuals and patients with, chronic medical conditions.

Prophylactic 5-Fr pancreatic duct stents are superior to 3-Fr stents: a randomized controlled trial.

BACKGROUND: Temporary prophylactic pancreatic duct stenting effectively reduces post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) in high-risk patients, but the optimal stent remains unclear. We compared rate of spontaneous passage, and technical difficulty of placement for 3-Fr and 5-Fr stents. METHODS: A randomized controlled trial at a single academic medical center. Patients deemed high risk for PEP randomly received 5-Fr or 3-Fr pancreatic duct stents. Primary outcome was spontaneous stent passage by 2 weeks. Secondary outcomes were ease and time for stent placement, and number of guide wires required for the entire procedure. RESULTS: Patients (69 female [89 %]; mean age 44.9 years, standard deviation [SD] 16.8) were randomly assigned to receive 5-Fr (n = 38) and 3-Fr (n = 40) stents. Indications for stenting were similar. Seven patients in the 3-Fr group actually received a 5-Fr stent, and two in the 5-Fr group had a 3-Fr stent. Spontaneous passage or non-passage was confirmed in 64 (83 %). No statistically significant difference in spontaneous passage rates was seen (5-Fr group, 68.4 %; 3-Fr group 75.0 %; P = 0.617). Non-passage rates were 10.5 % (5-Fr group) and 10.0 % (3-Fr group) ( P = 1.00). The study was stopped after a futility analysis for the primary end point. Placement of 5-Fr stents was rated easier, at a mean score of 1.8 (5-Fr) vs. 3.4 (3-Fr), P < 0.001, with a trend towards being faster, 9.2 vs. 11.1 minutes ( P = 0.355). Fewer guide wires were required for 5-Fr stent placement, 1.5 vs. 1.9 ( P = 0.002). PEP rates did not differ ( P = 0.519). CONCLUSION: Placement of 5-Fr compared to 3-Fr pancreatic duct stents for PEP prophylaxis is easier, faster, and requires fewer wires. No statistically significant difference in spontaneous passage was found between the two sizes.

Expression of 12-lipoxygenase as a biomarker for melanoma carcinogenesis.

12-Lipoxygenase (12-LOX), through its metabolite 12( )-hydroxyeicosatetraenoic acid [12( )-HETE], has been demonstrated to play a pivotal role in experimental melanoma invasion and metastasis, and 12-LOX expression may be important in early human melanoma carcinogenesis. We have studied the differences in 12-LOX protein expression during the progression of melanoma from human melanocytic cells to benign and dysplastic naevi to malignant metastatic disease. 12-LOX expression was determined in normal human skin melanocytes and in melanocytes found in compound naevi, dysplastic naevi and melanomas using a platelet-type 12-LOX antibody with a diaminobenzidine immunoperoxidase system detection system and was quantified using the analysis software NIH Image 1.62. Mean cellular pixel densities for 12-LOX staining ( = 50 cells/histological type) were unchanged in compound naevi ( = 0.14) and were increased in dysplastic naevi and melanomas compared with normal skin melanocytes ( = 0.03 and = 0.01, respectively). Similarly, melanomas had higher levels of expression compared with dysplastic naevi ( = 0.03). 12-LOX expression was significantly different between compound naevus and dysplastic naevus melanocytes ( = 0.01). These data suggest that 12-LOX may be an important novel marker for cancer progression within the melanoma system, and therefore could be a useful biomarker and therapeutic target for melanoma chemoprevention.

Definition of the supraclavicular and infraclavicular nodes: implications for three-dimensional CT-based conformal radiation therapy.

PURPOSE: To delineate with computed tomography (CT) the anatomic regions containing the supraclavicular (SCV) and infraclavicular (IFV) nodal groups, to define the course of the brachial plexus, to estimate the actual radiation dose received by these regions in a series of patients treated in the traditional manner, and to compare these doses to those received with an optimized dosimetric technique. MATERIALS AND METHODS: Twenty patients underwent contrast material-enhanced CT for the purpose of radiation therapy planning. CT scans were used to study the location of the SCV and IFV nodal regions by using outlining of readily identifiable anatomic structures that define the nodal groups. The brachial plexus was also outlined by using similar methods. Radiation therapy doses to the SCV and IFV were then estimated by using traditional dose calculations and optimized planning. A repeated measures analysis of covariance was used to compare the SCV and IFV depths and to compare the doses achieved with the traditional and optimized methods. RESULTS: Coverage by the 90% isodose surface was significantly decreased with traditional planning versus conformal planning as the depth to the SCV nodes increased (P < .001). Significantly decreased coverage by using the 90% isodose surface was demonstrated for traditional planning versus conformal planning with increasing IFV depth (P = .015). A linear correlation was found between brachial plexus depth and SCV depth up to 7 cm. CONCLUSION: Conformal optimized planning provided improved dosimetric coverage compared with standard techniques.

Dose escalation in non-small-cell lung cancer using three-dimensional conformal radiation therapy: update of a phase I trial.

PURPOSE: High-dose radiation may improve outcomes in non-small-cell lung cancer (NSCLC). By using three-dimensional conformal radiation therapy and limiting the target volume, we hypothesized that the dose could be safely escalated. MATERIALS AND METHODS: A standard phase I design was used. Five bins were created based on the volume of normal lung irradiated, and dose levels within bins were chosen based on the estimated risk of radiation pneumonitis. Starting doses ranged from 63 to 84 Gy given in 2.1-Gy fractions. Target volumes included the primary tumor and any nodes >or= 1 cm on computed tomography. Clinically uninvolved nodal regions were not included purposely. More recently, selected patients received neoadjuvant cisplatin and vinorelbine. RESULTS: At the time of this writing, 104 patients had been enrolled. Twenty-four had stage I, four had stage II, 43 had stage IIIA, 26 had stage IIIB, and seven had locally recurrent disease. Twenty-five received chemotherapy, and 63 were assessable for escalation. All bins were escalated at least twice. Although grade 2 radiation pneumonitis occurred in five patients, grade 3 radiation pneumonitis occurred in only two. The maximum-tolerated dose was only established for the largest bin, at 65.1 Gy. Dose levels for the four remaining bins were 102.9, 102.9, 84 and 75.6 Gy. The majority of patients failed distantly, though a significant proportion also failed in the target volume. There were no isolated failures in clinically uninvolved nodal regions. CONCLUSION: Dose escalation in NSCLC has been accomplished safely in most patients using three-dimensional conformal radiation therapy, limiting target volumes, and segregating patients by the volume of normal lung irradiated.

Immunogenetic therapy of human melanoma utilizing autologous tumor cells transduced to secrete granulocyte-macrophage colony-stimulating factor.

We performed a clinical study of five patients with melanoma to evaluate the immunobiological effects of retrovirally transduced autologous tumor cells given as a vaccine to prime draining lymph nodes. Patients were inoculated with both wild-type (WT) and GM-CSF gene-transduced tumor cells in different extremities. Approximately 7 days later, vaccine-primed lymph nodes (VPLNs) were removed. There was an increased infiltration of dendritic cells (DCs) in the GM-CSF-secreting vaccine sites compared with the WT vaccine sites. This resulted in a greater number of cells harvested from the GM-CSF-VPLNs compared with the WT-VPLNs at a time when serum levels of GM-CSF were not detectable. Four of five patients proceeded to have the adoptive transfer of GM-CSF-VPLN cells secondarily activated and expanded ex vivo with anti-CD3 MAb and IL-2. One patient had a durable complete remission of metastatic tumor. Utilizing cytokine (IFN-gamma, GM-CSF, IL-10) release assays, GM-CSF-VPLN T cells manifested diverse responses when exposed to tumor antigen in vitro. In two of two patients, GM-CSF-VPLN T cell responses were different from those of matched WT-VPLN cells. This study documents measurable immunobiologic differences of GM-CSF-transduced tumor cells given as a vaccine compared with WT tumor cells. The complete tumor remission in one patient provides a rationale to pursue this approach further.

Serum thyroglobulin levels after thyroxine withdrawal in patients with low risk papillary thyroid carcinoma.

We hypothesized that elevated levels of serum thyroglobulin (Tg) are frequently found as the only index of residual neoplasm in patients with low-risk papillary thyroid carcinoma. The records of patients operated on for papillary thyroid carcinoma over a 2-year period were reviewed, and the patients were allocated to risk groups by a validated staging method that does not include Tg levels. Of the 35 patients who manifested a low-risk carcinoma, 9 (26%) exhibited elevated Tg concentrations (11-53 ng/mL) during thyroxine withdrawal after therapies, while clinical, scintigraphic, and radiographic studies at least 1 year later showed no evidence of tumor. Prior scintigraphic imaging of therapeutic doses of 131I in 8 of 9 patients demonstrated no distant metastases, further confirming the low-risk status of this group. The staging method predicts that only 0.9% of patients with low-risk papillary carcinoma will have a cause specific death in 20 years. Elevated Tg concentrations have not been shown to forecast independently the survival of patients with low-risk papillary carcinoma. Thus, although frequently encountered, elevated Tg concentrations are unlikely to predict shortened survival in patients with papillary carcinoma for whom low risk has been determined from other data.

Immunological effects of BCG as an adjuvant in autologous tumor vaccines.

The role of Bacillus Colmette-Guérin (BCG) as an adjuvant in autologous tumor vaccines was examined. In nine patients with renal cell cancer, irradiated tumor cells alone (wild-type, WT) or with BCG were inoculated intradermally into contralateral thighs. Seven to 10 days later, the draining vaccine-primed lymph nodes (WT-VPLN and BCG-VPLN) were excised. BCG increased the number of harvested VPLN cells by 10-fold (mean +/- SE = 61.8 +/- 20.6/x10(-7)/patient). BCG-VPLN had significantly greater percentages of CD3(+) and CD4(+) T cells compared to WT-VPLN. Both groups of VPLN cells were activated in vitro with anti-CD3 or anti-CD3/CD28 mAbs followed by expansion in IL-2. Anti-CD3/CD28 activation resulted in greater expansion of CD4(+) T cells compared to anti-CD3. After activation, VPLN cells were stimulated with irradiated autologous tumor targets and cytokines (IFN-gamma, GM-CSF, IL-10) released into the supernatants were measured 24 h later. Anti-CD3/CD28-activated BCG-VPLN cells were found to have a greater release of IFN-gamma compared with that of WT-VPLN cells, which was not observed significantly with IL-10 or GM-CSF. BCG resulted in increased VPLN cell yield as well as enhanced type 1 (IFN-gamma release) immune responses of VPLN cells to autologous tumor without upregulating type 2 (IL-10 release) responses. Anti-CD3/CD28 was superior to anti-CD3 activation in this cellular response.

The multidisciplinary melanoma clinic: a cost outcomes analysis of specialty care.

The traditional process of melanoma care delivery can differ substantially among providers regarding screening laboratories, staging work-ups, surgical margins, and outpatient versus inpatient surgical management. It has been suggested that multidisciplinary care may provide a more cost-effective management approach. We sought to evaluate whether coordinated multidisciplinary melanoma care that follows evidence-based, consensus-approved clinical practice guidelines at a large academic medical center can provide a more efficient alternative to traditional community-based strategies with clinical outcomes that are at least equivalent. The University of Michigan Multidisciplinary Melanoma Clinic (MDMC) possesses a database of demographic, clinical, and treatment information for all patients seen since its inception. A consecutive sample of 104 patients with local disease who were treated in the Michigan community were compared with 104 blindly selected subjects treated at the MDMC during an identical time period, matched for Breslow depth and melanoma body site. Patients treated in the MDMC would save a third party payer roughly $1600 per patient when compared with a similar group treated in the Michigan community. Surgical morbidity, length of hospitalization, and long-term survival of MDMC patients were similar to those reported in the literature. The cost discrepancy is explained by the fundamental differences in the usage pattern of health care resources exhibited by the MDMC compared with the community setting.

A novel approach to assess changes in endocrine secretion: analysis of GnRH antagonist (Nal-Glu) suppression of gonadotropin release in ovariectomized ewes.

Circulating hormone levels reflect the outcome of multiple feedback systems. A method to accurately assess the dynamics of hormonal changes in samples collected at infrequent intervals and compare these dynamic processes among treatment groups is presented. In this approach, a smooth curve is fitted to each time series of concentrations produced in an experiment, the curves are summarized by numerical measurements, and the measurements are subjected to statistical analysis. The method is demonstrated on data from an experiment that explores the differential effects of a competitive GnRH receptor antagonist (Nal-Glu) on circulating levels of LH and FSH. In this experiment, six adult ovariectomized Suffolk ewes were treated with one of three doses of Nal-Glu using a crossover design. LH and FSH concentrations were determined in hourly samples of jugular blood for 24 h after treatment. Applying the analytical approach, we observed differential effects of increasing concentrations of Nal-Glu on circulating LH and FSH concentrations. The magnitude of LH suppression was similar from dose to dose, while the duration of LH suppression was dose-dependent. In contrast, all doses of Nal-Glu elicited similar effects on the amplitude, duration and time to recovery of FSH suppression. Studies conducted in vitro utilizing dispersed ovine pituitary cells in culture demonstrated that the differential effects of Nal-Glu on FSH and LH secretion were not the outcome of differential sensitivity of FSH and LH to GnRH. The differential effects of Nal-Glu on circulating LH and FSH concentrations may be due to a number of factors, including other releasing or release-inhibiting hormones, paracrine modulators involved in selective regulation of FSH, and/or differences in clearances.

Adoptive immunotherapy with vaccine-primed lymph node cells secondarily activated with anti-CD3 and interleukin-2.

PURPOSE: In preclinical studies, we have reported the ability to induce immune T cells in lymph nodes (LN) primed by in vivo vaccination with tumor cells admixed with a bacterial adjuvant. These LN cells can be activated and expanded ex vivo for the successful immunotherapy of established tumors. We have applied these methods to generate vaccine-primed LN in patients with advanced melanoma and renal cell cancer (RCC) for therapy. MATERIALS AND METHODS: Irradiated autologous tumor cells admixed with bacille Calmette-Guérin (BCG) were used to vaccinate patients. Seven days later, draining LN were removed for activation with anti-CD3 monoclonal antibody (mAb) followed by expansion in interleukin-2 (IL-2). Activated LN cells were administered intravenously (IV) with the concomitant administration of IL-2. RESULTS: A total of 23 patients were evaluated (11 melanoma and 12 RCC). Vaccine-primed LN were expanded ex vivo with a mean of 8.4 x 10(10) cells administered per patient. Among 20 patients assessed, 15 demonstrated minimal cytotoxicity of autologous tumor cells by the activated LN cells, with the remaining mediating nonspecific cytotoxicity. By contrast, a majority of the activated LN cells showed highly specific release of granulocyte-macrophage colony-stimulating factor (GM-CSF) and interferon gamma (IFN-gamma) to autologous but not allogeneic tumor stimulation. This tumor-specific cytokine release was found to be major histocompatibility complex (MHC) class I-restricted, which indicates the involvement of CD8+ cells. Among 11 melanoma patients, one had a partial tumor response. Among 12 RCC patients, two had complete and two partial responses. A trend (P = .066) between the enhancement of delayed-type hypersensitivity (DTH) reactivity to autologous tumor after therapy and tumor regression was observed. CONCLUSION: Tumor vaccines can be used to induce immunologically specific T-cell responses against melanoma and RCC in draining LN. Anti-CD3/IL-2 activation of primed LN cells can be reliably performed for clinical therapy and appears to have activity in patients with metastatic RCC.

Effect of bromodeoxyuridine on radiation-induced DNA damage and repair based on DNA fragment size using pulsed-field gel electrophoresis.

We have used biphasic linear ramping pulsed-field gel electrophoresis (PFGE) to understand the effect of incorporation of bromodeoxyuridine (BrdUrd) on radiation-induced DNA damage and repair. This technique permits a determination of the fragment size distribution produced immediately after irradiation as well as during the repair period. We found that incorporation of BrdUrd increased the induction and decreased the repair of radiation damage. The fragment size distribution was consistent with a random breakage model. When we found that significantly more damage was detected after irradiation of deproteinized DNA compared to intact cells, we studied the effects of BrdUrd incorporation on the radiation response of cells or DNA at various phases of preparation for electrophoresis: cells adherent to the culture dish (A), trypsinized cells (B), agarose-embedded cells (C) and deproteinized DNA (D). Although there was a general tendency to detect more damage when irradiation was performed later in the preparation process, steps B and C were the only successive steps which were significantly different. These findings demonstrate that incorporation of BrdUrd randomly increases the induction of radiation damage and decreases its repair at the level of 200 kbp to 5 Mbp fragments. Furthermore, they confirm that the amount of damage detected depends upon the conditions of the cells or DNA at the time of irradiation.

A double-blind, randomized, placebo-controlled trial of prostaglandin E1 in liver transplantation.

A double-blind placebo-controlled trial of intravenous prostaglandin PGE1 (40 micrograms/h) was conducted in adult orthotopic liver transplant recipients. Infusion was started intraoperatively and continued for up to 21 days. Patients were followed up for 180 days postoperatively. Among 172 patients eligible for treatment in the study, 160 could be evaluated (78 PGE1; 82 placebo). Patient and graft survival were similar (PGE1: 16 deaths, 9 retransplantations [7 survivors]; controls: 15 deaths, 6 retransplantations [3 survivors]). In patients with surviving grafts, however, PGE1 administration resulted in a 23% shorter mean duration of hospitalization following transplantation (PGE1: 24.4 days; controls: 31.8 days; P = .02) and a 40% shorter length of time postoperatively in the intensive care unit (PGE1: 8.2 days; controls 13.7 days; P = .05). Reduced needs for renal support (P = .03) or surgical intervention other than retransplantation (P = .02) were also noted with PGE1 use. Further, PGE1 administration resulted in a trend toward improved survival rates in patients with mild renal impairment (preoperative serum creatinine 1.5 mg percent or greater; P = .08). Neither the incidence of acute cellular rejection nor of primary nonfunction was significantly different in the two groups. Phlebitis was the only complication that was more common during PGE1 administration, (PGE1: 9; controls: 4). These results suggest that PGE1 use in hepatic allograft recipients reduces morbidity and may result in sizable cost reductions.

Use of fluorescence in situ hybridization (FISH) to study chromosomal damage induced by radiation and bromodeoxyuridine in human colon cancer cells.

PURPOSE: Although the thymidine analog radiation sensitizer bromodeoxyuridine (BrdUrd) increases radiation-induced chromosomal aberrations, it is not known whether these aberrations are uniformly distributed among chromosomes. Using fluorescence in situ hybridization, we carried out a study to test the hypothesis that BrdUrd-induced radiosensitization may be mediated by nonuniform chromosomal damage. METHODS AND MATERIALS: Log phase HT29 human colon cancer cells were exposed to 10 microM BrdUrd (or media alone) for one cell cycle, and the G1 cells were separated by centrifugal elutriation. Half of the control and BrdUrd samples were irradiated with 8 Gy. Cells were then incubated for 24-28 h, and metaphase spreads were prepared. Fluorescence in situ hybridization was performed using paint probes for chromosomes 1 and 4. RESULTS: We found that radiation induced 0.20 aberrations per chromosome in chromosome 4. Based on the ratio of the relative lengths of chromosome 1-4 (1.34), it was predicted that chromosome 1 would have approximately 0.26 aberrations per chromosome. However, we observed 0.39 aberrations per chromosome 1, which was significantly greater than the predicted (p < 0.001 by chi-square). Incubation with BrdUrd prior to irradiation significantly increased the aberrations found in chromosome 1 (by a factor of 1.4) and chromosome 4 (by a factor of 1.9) compared to radiation alone (p < 0.001) for both chromosome 1 and 4). CONCLUSION: This study demonstrates that individual chromosomes in human colon cancer cells show significantly different rates of aberration after irradiation. Furthermore, the BrdUrd-mediated increase in radiation-induced chromosomal aberrations may not be uniform among chromosomes.

Identification of aperiodic seasonality in non-Gaussian time series.

Time series that arise from biological experimentation can exhibit seasonality where the lengths of the seasons may vary. In addition, such time series may not be stationary with respect to either mean, variance, or autocorrelation, thus making the usual waveform-fitting techniques inappropriate. An agglomerative clustering algorithm for identifying seasons in such series is proposed, consisting of an initialization step, iterative steps where clusters are combined into larger clusters, and a stopping rule for the iteration. The clusters can be associated with seasons or phases, and biological cycles can be identified from the phases. Results of a simulation and an analysis of luteinizing hormone concentrations are presented.

P450 3A activity and cyclosporine dosing in kidney and heart transplant recipients.

Interpatient differences in the kinetics of cyclosporine appear to result in part from interindividual differences in the catalytic activity of an enzyme termed P450 3A. We investigated the relationship between P450 3A activity, as measured by the erythromycin breath test (ERMBT), and the appropriate stable daily dose of cyclosporine as currently determined by physicians at our institution. The ERMBT was administered to kidney and heart allograft recipients who had attended at least two monthly clinic visits without having their daily cyclosporine dose changed. There was a significant positive correlation between the ERMBT result and the daily cyclosporine doses (in milligrams per kilogram) in both the heart (r = 0.68; p = 0.04; n = 9) and kidney (r = 0.68; p = 0.03; n = 10) recipients. To confirm our findings, we prospectively administered the ERMBT on multiple occasions to 20 patients who were undergoing kidney transplantation. Although the transplant physicians were blinded to the ERMBT results, the test predicted the stable daily doses of cyclosporine that they ultimately prescribed to the patients (r = 0.54; p = 0.015). When data from all 39 patients were pooled and subjected to multiple regression analysis, the ERMBT was the only variable examined that significantly correlated with the stable daily cyclosporine dose (r = 0.63; p < 0.001; n = 39). In the 20 patients prospectively studied, the prescribed daily dose of cyclosporine generally decreased during the months after surgery and the percentage changes in cyclosporine daily dose correlated with changes in P450 3A activity during this period (r = 0.47; p = 0.03).(ABSTRACT TRUNCATED AT 250 WORDS)

Predictors of toxicity in treating patients with neuroblastoma by radiolabeled metaiodobenzylguanidine.

We searched for methods that would enable prescriptions of the maximum tolerable doses of iodine-131 metaiodobenzylguanidine (MIBG) and iodine-125 MIBG in the treatment of patients with neuroblastoma. We correlated doses, defined in different ways, with subsequent platelet levels in treated patients to determine accurate predictors of the most frequent toxicity, thrombocytopenia. Nine patients with neuroblastoma were given 131I-MIBG (4.9-8.1 GBq or 132-220 mCi) and ten were given 125I-MIBG (8.3-30.0 GBq or 224-809 mCi) as initial treatments. These therapies were sufficiently varied that correlations could be made between indices of the doses and the subsequent toxicity as reflected in circulating platelet levels. Predictors of toxicity were: whole-body absorbed dose of radiation (cGy) calculated from pretherapy tracer doses of 131I-MIBG; GBq/kg of body weight; and GBq/m2 of body surface area. Toxicity was recorded as the nadir of the platelet level and platelet/pretherapeutic level (platelet ratio). For treatments with 131I-MIBG, the highest correlation was obtained between cGy and the log10-transformed platelet ratio (r = -0.86), but comparison of GBq/m2 and the platelet nadir (r = -0.76) or the platelet ratio (r = -0.74) or the log10 transformed platelet ratio (r = -0.73) gave comparable and statistically significant results. For treatments with 125I-MIBG, significant correlations were obtained between GBq/m2 and the platelet ratio (r = -0.81) or GBq/kg and the log10-transformed platelet ratio; the correlation between cGy and any toxicity index was low. Per administered GBq, 131I-MIBG was 2.6 times more potent than 125I-MIBG in causing a platelet ratio of 0.1.(ABSTRACT TRUNCATED AT 250 WORDS)

An algorithm for robust non-linear analysis of radioimmunoassays and other bioassays.

The four-parameter logistic function is an appropriate model for many types of bioassays that have continuous response variables, such as radioimmunoassays. By modelling the variance of replicates in an assay, one can modify the usual parameter estimation techniques (for example, Gauss-Newton or Marquardt-Levenberg) to produce parameter estimates for the standard curve that are robust against outlying observations. This article describes the computation of robust (M-) estimates for the parameters of the four-parameter logistic function. It describes techniques for modelling the variance structure of the replicates, modifications to the usual iterative algorithms for parameter estimation in non-linear models, and a formula for inverse confidence intervals. To demonstrate the algorithm, the article presents examples where the robustly estimated four-parameter logistic model is compared with the logit-log and four-parameter logistic models with least-squares estimates.

The use of biphasic linear ramped pulsed field gel electrophoresis to quantify DNA damage based on fragment size distribution.

PURPOSE: The development of biphasic linear pulse ramping gel electrophoresis has permitted resolution of DNA fragments from 200 Kbp to 6 Mbp in a single gel. We used this technique to measure radiation-induced DNA damage based on fragment size. METHODS AND MATERIALS: Human colon cancer cells (HT29 and LS174T) and Chinese hamster ovary cells were embedded in agarose, deproteinized, irradiated with 5-80 Gy, and assessed for DNA double strand breakage using pulsed field gel electrophoresis. The frequency of DNA double strand breakage determined using a previously published method was compared to the breakage frequency calculated using the fragment size distribution. RESULTS: Both methods produced similar estimates for breakage frequency of approximately 5 x 10(-9) breaks Gy-1 bp-1. CONCLUSIONS: These findings suggest that biphasic linear pulse ramping gel electrophoresis can yield a quantitative estimate of DNA fragment distribution resulting from irradiation. The ability to quantify the distribution of DNA fragment sizes produced by irradiation should yield important information concerning the mechanisms of both DNA double strand break induction and repair.

Correlation of the local and systemic cytokine response with clinical outcome following thermal injury.

Eighty-eight patients with acute thermal injury were evaluated. Forty-eight hours after injury, TNF, IL-6, and IL-8 were significantly present in the systemic circulation, lung, normal skin, and thermally injured skin. The presence of TNF, IL-6, and IL-8 proteins in the lung, normal skin, and thermally injured skin were associated with TNF, IL-6, and IL-8 mRNA upregulation. Logistic regression analysis controlling for the Abbreviated Burn Severity Index demonstrated that the presence of IL-8 in the lung was associated with early pulmonary physiologic dysfunction (p = 0.006) and nosocomial pulmonary infection (p = 0.040). We conclude that acute thermal injury initiates an early systemic, lung, and skin response involving TNF, IL-6, and IL-8. The TNF, IL-6, and IL-8 protein present in the lung and skin in response to acute thermal injury are generated locally and do not originate from the systemic cytokine pool. The lung cytokine response to acute thermal injury may initiate local organ failure.