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Biomedical subjects

J E Anderson

Publications and source records attributed to J E Anderson.

At least 37 records · Page 2Linked to original sources

Effect of selective internal radiation therapy and hepatic arterial chemotherapy on normal liver volume and spleen volume.

OBJECTIVE: To determine the effect of selective internal radiation therapy (SIRT) and hepatic arterial chemotherapy (HAC) on normal liver volume and spleen volume in patients receiving these treatments for advanced liver cancer. METHODS: In a phase III clinical trial to assess the benefit of SIRT over HAC one group of patients received SIRT + HAC while a second group received HAC only. All patients in this trial who had abdominal CT scans available before treatment, and at 3, 6, and 12 months after treatment were evaluated. Changes in normal hepatic parenchyma (NHP) volume, portal vein diameter and spleen volume were calculated for each patient and analysed for significant trends. RESULTS: The mean NHP volume decreased by 17% (P = 0.001) 12 months after treatment among patients receiving SIRT + HAC (N = 22), while the mean NHP volume among patients treated with HAC only (N = 15) was unchanged at 12 months. The mean portal vein diameter increased by 9% in both treatment groups, P = 0.048 and P < 0.001, respectively. The mean spleen volume increased by 48% (P < 0.001) and 26% (P = 0.001), respectively, in the two groups 12 months after treatment started. There was no clinical evidence of hepatic failure, portal hypertension or splenic dysfunction in any of the patients. CONCLUSIONS: Treatment of patients with SIRT + HAC causes contraction of the normal hepatic parenchyma, while treatment with HAC alone has no significant effect. Treatment with either SIRT + HAC or HAC alone causes a significant increase in portal vein diameter and spleen volume by 12 months after treatment. The increase in spleen volume and portal vein size is likely to be due to portal hypertension resulting from scarring within the liver as a result of chemical and radiation hepatitis.

Aged↗

Degradation of maternal cdc25c during the maternal to zygotic transition is dependent upon embryonic transcription.

To gain a better understanding of the molecular differences that may contribute to cleavage arrest and the poorer development associated with laboratory produced embryos, a series of experiments were conducted to quantitate the message levels of the cell cycle controller cdc25c, over the maternal to zygotic transition (MZT) in 4-cell in vivo- and in vitro-derived porcine embryos. The experiments were designed to measure both maternal and embryonic derived cdc25c transcripts by quantitative reverse transcription-competitive polymerase chain reaction (RT-cPCR), determine the point of the transition to zygotic genome activation, and study the interaction between initial embryonic transcription and maternal cdc25c degradation. Analysis of in vivo- and in vitro-derived embryos revealed no difference in cdc25c message level for any of the times P4CC (P > 0.05). Comparison of control embryos from 5- to 33-hr P4CC revealed a reduction in transcript quantities in the 10-hr P4CC group that was maintained at later time points (P < 0.05). Embryos cultured in the RNA polymerase inhibitor, alpha-amanitin, from cleavage to 5-, 10-, 18-, 25-, or 33-hr P4CC displayed no difference in cdc25c levels when compared to controls at similar time points (P > 0.05). However, if embryos were first exposed to alpha-amanitin after 18-hr P4CC with this treatment continuing to 33 hr, the levels of cdc25c transcript were reduced (P < 0.04) when compared to those embryos that were first exposed to the inhibitor at either 5- or 10-hr P4CC. This finding and the comparison of these same embryos to the 0-33-hr alpha-amanitin and control groups allowed us to conclude that cdc25c transcription began between 10- and 18-hr P4CC, with the degradation of maternal cdc25c message dependent on transcriptional initiation.

Amanitins↗

Determination of the onset of crystallization of N1-2-(thiazolyl)sulfanilamide (sulfathiazole) by UV-Vis and calorimetry using an automated reaction platform; subsequent characterization of polymorphic forms using dispersive Raman spectroscopy.

This work describes the use of UV/visible spectroscopy and calorimetry to follow the onset of crystallization of a commercially available compound, N(1)-2-(thiazolyl)sulfanilamide (sulfathiazole), during crystallization reactions performed using an automated reaction platform. Sulfathiazole has been the subject of numerous publications through which considerable confusion about the morphic form is apparent. This work does not attempt to investigate exhaustively the polymorph issue, but rather to exploit the use of the HEL auto-MATE for monitoring the onset of crystal formation. Real-time calorimetry and UV-Vis spectroscopy are compared as tools for determining the onset of crystallization. Subsequently, differential scanning calorimetry, dispersive Raman, and infrared spectroscopy analysis serve to identify the crystal forms generated by the HEL auto-MATE. A solvent-anti-solvent matrix and several bench-top crystallization experiments were performed to supplement the investigation in terms of generating the desired polymorphs.

Ammonia↗

Strike while the iron is hot: can stepped-care treatments resurrect relapsing smokers?

The efficacies of 2 group counseling step-up treatments for smoking cessation, cognitive-behavioral/skill training therapy (CBT) and motivational interviewing/supportive (MIS) therapy, were compared with brief intervention (BI) treatment in a sample of 677 smokers. Differential efficacy of the 2 step-up treatments was also tested in smokers at low and high risk for relapse (no smoking vs. any smoking during the first postquit week. respectively). All participants received 8 weeks of nicotine patch therapy. BI consisted of 3 brief individual cessation counseling sessions; CBT and MIS participants received BI treatment and 6 group counseling sessions. Neither CBT nor MIS treatment improved long-term abstinence rates relative to BI. Limited support was found for the hypothesis that high-risk smokers would benefit more from MIS than CBT. Other hypotheses were not supported.

Administration, Cutaneous↗

Relapse after allogeneic bone marrow transplantation for refractory anemia is increased by shielding lungs and liver during total body irradiation.

Patients with the refractory anemia (RA) subtype of myelodysplastic syndrome who undergo allogeneic bone marrow transplantation (BMT) have a low risk of relapse, but they have a high risk of nonrelapse mortality when prepared with conventional preparative regimens. To try to reduce nonrelapse mortality, we treated 14 RA patients with a modified approach to total body irradiation (TBI) followed by cyclophosphamide (CY) and HLA-identical sibling BMT. Median patient age was 44 years (range, 28 to 65 years). Patients received TBI with shielding of the right lobe of the liver and both lungs followed by electron beam boosts to shielded ribs. Total radiation exposure in nonshielded areas was 12 Gy (n = 10), 10 Gy (n = 3), or 6 Gy (n = 1). After TBI, patients received CY at 120 mg/kg over 2 days, followed by transplantation of unmanipulated bone marrow. All patients initially achieved engraftment with donor cells, although 2 patients had subsequent reemergence of host hematopoiesis without evidence of disease relapse. Five patients died of transplantation-related causes between 22 and 1262 days post-BMT. Four patients relapsed between 157 and 1096 days post-BMT. These 14 patients were compared with 46 historical controls with RA who received conventional CY/TBI or busulfan/CY preparative regimens. Patients in the experimental group had a similar nonrelapse mortality rate compared with the historical control group (29% versus 37%, respectively; P = .8), but a higher relapse rate (34% versus 2%, P = .0004) and a lower disease-free survival (38% versus 61%, P = .16). We conclude that this modified TBI approach is associated with an unacceptably high risk of relapse for patients with RA undergoing BMT.

Adult↗

An assessment of various household food security measures in Hawaiì has implications for national food security research and monitoring.

The Core Food Security Module (CFSM), the national food security monitoring tool, requires three affirmative responses to categorize households as food insecure. If this tool is unreliable or inaccurate, vulnerable segments of our population may be adversely affected. The objectives of the present study were to assess the credibility of applying the CFSM categorical measure to a population sample from Hawaiì and to assess the concurrent validity of the CFSM, the new face-valid measure and measures adapted from the Radimer/Cornell (RC) measure and Community Childhood Hunger Identification Project. The sample included 1469 respondents gathered through a statewide telephone sample and 144 food pantry recipients. Responses to the 18 CFSM questions were used to create all four measures. The credibility of the CFSM categorical measure was also assessed via comparisons with individual items and with the 1995 national modal CFSM response pattern. Categorical measures were compared across food security prevalence estimates and indices of income and vegetable intake and with the CFSM scale measure. Differences in the modal response pattern between samples affected CFSM categorization. Only 36% of households followed the Hawaiì modal response pattern, and categorization was not consistent with the content of key items. Although 85% of the households were classified as food secure by the CFSM, only 78% were classified as food secure with each of the other food security measures. Concurrent validity of all measures was confirmed. A reassessment of the national CFSM categorical measure appears warranted.

Adult↗

Metabolic adaptations in skeletal muscle overexpressing GLUT4: effects on muscle and physical activity.

To understand the long-term metabolic and functional consequences of increased GLUT4 content, intracellular substrate utilization was investigated in isolated muscles of transgenic mice overexpressing GLUT4 selectively in fast-twitch skeletal muscles. Rates of glycolysis, glycogen synthesis, glucose oxidation, and free fatty acid (FFA) oxidation as well as glycogen content were assessed in isolated EDL (fast-twitch) and soleus (slow-twitch) muscles from female and male MLC-GLUT4 transgenic and control mice. In male MLC-GLUT4 EDL, increased glucose influx predominantly led to increased glycolysis. In contrast, in female MLC-GLUT4 EDL increased glycogen synthesis was observed. In both sexes, GLUT4 overexpression resulted in decreased exogenous FFA oxidation rates. The decreased rate of FFA oxidation in male MLC-GLUT4 EDL was associated with increased lipid content in liver, but not in muscle or at the whole body level. To determine how changes in substrate metabolism and insulin action may influence energy balance in an environment that encouraged physical activity, we measured voluntary training activity, body weight, and food consumption of MLC-GLUT4 and control mice in cages equipped with training wheels. We observed a small decrease in body weight of MLC-GLUT4 mice that was paradoxically accompanied by a 45% increase in food consumption. The results were explained by a marked fourfold increase in voluntary wheel exercise. The changes in substrate metabolism and physical activity in MLC-GLUT4 mice were not associated with dramatic changes in skeletal muscle morphology. Collectively, results of this study demonstrate the feasibility of altering muscle substrate utilization by overexpression of GLUT4. The results also suggest that as a potential treatment for type II diabetes mellitus, increased skeletal muscle GLUT4 expression may provide benefits in addition to improvement of insulin action.

Animals↗

Developing standards in behavioral surveillance for HIV/STD prevention.

HIV/STD prevention programs are increasingly guided by behavioral rather than by disease indicators. Relevant HIV/STD-related behavioral information is currently available from a variety of surveys and surveillance systems at three levels: general population, infected populations, and high-risk populations. However, the utility of these systems for local program development is limited due to lack of standardization. In 1997 a Centers for Disease Control and Prevention working group was formed to develop a core set of items for HIV/STD behavioral surveillance for use across surveys. Core items were chosen on the basis of existing surveys and surveillance systems, relevant literature, testing in a cognitive laboratory, and field pilot-testing. A draft of the core set of sexual behavior questions is available on the web at http://www.cdc.gov/nchstp/od/core-workgroup for review and feedback. Questions on drug use, including drug injection practices, as well as questions on HIV testing and sexually transmitted diseases are in preparation and will also be posted on the web site for review.

Centers for Disease Control and Prevention, U.S.↗

Allogeneic and syngeneic marrow transplantation for myelodysplastic syndrome in patients 55 to 66 years of age.

We carried out bone marrow transplantation (BMT) in 50 patients with myelodysplastic syndrome (MDS) who were 55.3 to 66.2 years of age (median, 58.8 years). According to the criteria of the French-American-British (FAB) classification, 13 patients had refractory anemia (RA), 19 had RA with excess blasts (RAEB), 16 had RAEB in transformation or acute myelogenous leukemia (RAEB-T/AML), and 2 had chronic myelomonocytic leukemia (CMML). According to the recently established International Prognostic Scoring System (IPSS), available for 45 patients, 2 patients were considered low risk; 14, intermediate 1 risk; 19, intermediate 2 risk; and 10, high risk. Conditioning regimens were cyclophosphamide (CY) (120 mg/kg of body weight) plus 12-Gy fractionated total-body irradiation (FTBI) (n = 15), CY plus FTBI with lung and liver shielding (n = 4), busulfan (7 mg/kg) plus FTBI (n = 4), or busulfan (16 mg/kg) plus CY (n = 27). The busulfan-plus-CY group included 16 patients in whom busulfan was targeted to plasma levels of 600 to 900 ng/mL. In these 16 patients, steady-state levels of busulfan actually achieved were 714 to 961 ng/mL (mean +/- SD, 845 +/- 64 ng/mL; median, 838 ng/mL). The donors were HLA-identical siblings for 34 patients, HLA-nonidentical family members for 4, identical twins for 4, and unrelated volunteers for 6. All 46 patients surviving > 21 days had engraftment, and 22 patients (44%) are surviving 9 to 80 months after BMT. Specifically, among 13 patients with RA, 1 had relapse (cumulative incidence [CI] at 3 years, 8%) and 8 are surviving, for a Kaplan-Meier (KM) estimate of survival at 3 years of 59% (disease-free survival [DSF], 53%). Among 19 patients with RAEB, 3 had relapse (CI at 3 years, 16%), and 8 are surviving disease free (KM estimate at 3 years, 46%). Among 18 patients with RAEB-T/AML or CMML, 6 had relapse (CI at 3 years, 28%), and the KM estimate of DSF at 3 years is 33%. Relapse-free survival had an inverse correlation with cytogenetic risk classification and with the risk score according to the IPSS. Survival in all FAB categories was highest among patients enrolled in a protocol in which busulfan plasma levels were targeted to 600 to 900 ng/mL. These data indicate that BMT can be carried out successfully in patients with MDS who are older than 55 years of age. (Blood. 2000;95:1188-1194)

Aged↗

Successful percutaneous stenting of a right gastroepiploic coronary bypass graft using monorail delivery system: a case report.

The right gastroepiploic artery (RGEA) is being successfully used as an arterial conduit in a selected group of patients undergoing coronary artery bypass graft surgery. However, myocardial ischemia may result due to spasm, occlusion, and stenosis of this graft. The anastamosis site at distal right coronary artery (RCA) or posterior descending artery (PDA) is the most common location for stenosis of an in situ gastroepiploic coronary bypass graft. Balloon angioplasty of such stenoses has been reported with optimal short-term results. Stent deployment would decrease the restenosis rate, so that repeat procedures could be minimized for these technically challenging lesions. We describe a case of successful deployment of a stent with monorail delivery system at the anastamotic site stenosis of an in situ gastroepiploic right coronary artery bypass graft. This percutaneous coronary intervention could prevent redo coronary artery bypass graft surgery. Cathet. Cardiovasc. Intervent. 49:197-199, 2000.

Angioplasty, Balloon, Coronary↗

A phase I study of induction chemotherapy for older patients with newly diagnosed acute myeloid leukemia (AML) using mitoxantrone, etoposide, and the MDR modulator PSC 833: a southwest oncology group study 9617.

Older patients with acute myelogenous leukemia (AML) have overexpression of P-glycoprotein (Pgp+), and this has been shown to correlate quantitatively with therapeutic outcome. Since Pgp-mediated efflux of cytotoxic drugs can be inhibited by the cyclosporine analogue, PSC 833, we investigated the use of this agent with a 5-day mitoxantrone/etoposide regimen in patients over age 55 with newly diagnosed AML. Previous studies suggested a 33% incidence of grade IV/V non-hematologic toxicity with the use of mitoxantrone 10 mg/M(2) and etoposide 100 mg/M(2), each for 5 days, in this patient population. Since PSC 833 alters the pharmacokinetic excretion of MDR-related cytotoxins, this phase I dose-finding study was performed to identify doses of mitoxantrone/etoposide associated with a similar 33% incidence of grade IV/V non-hematologic toxicity, when given with PSC 833. Mitoxantrone/etoposide (M/E) doses were escalated in fixed ratio from a starting dose of M: 4 mg/M(2) and E: 40 mg/M(2), to M: 7 mg/M(2) and E: 70 mg/M(2), in successive cohorts of eight patients each. PSC 833 was well tolerated and the MTD of this M/E regimen with PSC 833 in this population was M: 6 mg/M(2) and E: 60 mg/M(2). The complete response (CR) rate for all patients was 50% (15/30) and was considerably higher for de novo than for secondary AML. These data suggest that the addition of PSC 833 to an M/E regimen for older patients with untreated AML is well tolerated but requires a reduction in M/E dosing to avoid increased toxicity.

Acute Disease↗

Treatment of chronic myelomonocytic leukaemia by allogeneic marrow transplantation.

We evaluated the outcome of allogeneic bone marrow transplantation (BMT) in 21 patients with chronic myelomonocytic leukaemia (CMML) who were treated at the Fred Hutchinson Cancer Research Center between 1990 and 1998. There were 11 male and 10 female patients with a median age of 47.4 years (range 1.0-62.9). Patients were conditioned either with total body irradiation (TBI) and chemotherapy, with or without antithymocyte globulin (n = 19), or with chemotherapy alone (n = 2). The marrow donor was an HLA-identical sibling in 12 patients, an HLA-non-identical related donor in three patients and an unrelated volunteer donor in six patients. All evaluable patients achieved sustained engraftment. Fifteen patients developed grades II-IV acute graft-versus-host disease (GVHD). Nine patients (43.0%) are surviving disease free at 0.7-8.1 years (median 6.9) after transplantation. Five patients relapsed 75-660 d after transplant and all died. Five patients died with organ failure and two died with GVHD and associated infections. The Kaplan-Meier estimates of disease-free survival and relapse at 3 years were 39% and 25% respectively. The probability of survival was improved in patients with shorter disease duration compared with those with a long interval from diagnosis to BMT. Thus, as with other myeloproliferative diseases or myelodysplastic syndromes, BMT offers curative therapy for a proportion of patients with CMML. We suggest that patients with CMML who have a suitable donor should be considered for transplantation, probably early in their disease course. However, it will be important to develop new regimens with enhanced antileukaemic efficacy without further increasing regimen-related toxicity and mortality.

Adolescent↗

Bone marrow transplantation for myelodysplasia.

Allogeneic bone marrow transplantation (BMT) is the only treatment modality that has consistently been demonstrated to cure patients with the myelodysplastic syndrome (MDS). Since the early 1980s, numerous publications have reported the results with BMT for over 700 patients with MDS and the lead patients are now disease-free for more than 16 years. Overall, these studies show that approximately 40% of patients are likely to be cured with allogeneic BMT. The best results have been reported for patients with refractory anemia who receive marrow from fully matched related donors, with 75% long-term disease-free survival rates. Factors that are associated with an increased risk of relapse and, thereby, shorter disease-free survival, include increased blast percentage and poor risk karyotype. Factors that are associated with an increased risk of non-relapse mortality and, in some studies, shorter disease-free survival, include longer disease duration, advanced patient age, therapy-related MDS, male patients, and use of mismatched or unrelated donors. However, favorable results have been seen in small studies of patients 55-66 years of age and in patients with refractory anemia undergoing matched unrelated donor BMT. Allogeneic BMT is appropriate therapy for patients with high or intermediate risk disease (risk category based on the International Prognostic Scoring System). The use of allogeneic BMT for patients with low risk disease is not well defined, but may be appropriate for particularly young individuals or those with a life-threatening single cytopenia.

Bone Marrow Transplantation↗

A role for nitric oxide in muscle repair: nitric oxide-mediated activation of muscle satellite cells.

Muscle satellite cells are quiescent precursors interposed between myofibers and a sheath of external lamina. Although their activation and recruitment to cycle enable muscle repair and adaptation, the activation signal is not known. Evidence is presented that nitric oxide (NO) mediates satellite cell activation, including morphological hypertrophy and decreased adhesion in the fiber-lamina complex. Activation in vivo occurred within 1 min after injury. Cell isolation and histology showed that pharmacological inhibition of nitric oxide synthase (NOS) activity prevented the immediate injury-induced myogenic cell release and delayed the hypertrophy of satellite cells in that muscle. Transient activation of satellite cells in contralateral muscles 10 min later suggested that a circulating factor may interact with NO-mediated signaling. Interestingly, satellite cell activation in muscles of mdx dystrophic mice and NOS-I knockout mice quantitatively resembled NOS-inhibited release of normal cells, in agreement with reports of displaced and reduced NOS expression in dystrophin-deficient mdx muscle and the complete loss of NOS-I expression in knockout mice. Brief NOS inhibition in normal and mdx mice during injury produced subtle alterations in subsequent repair, including apoptosis in myotube nuclei and myotube formation inside laminar sheaths. Longer NOS inhibition delayed and restricted the extent of repair and resulted in fiber branching. A model proposes the hypothesis that NO release mediates satellite cell activation, possibly via shear-induced rapid increases in NOS activity that produce "NO transients."

Animals↗

The core food security module scale measure is valid and reliable when used with Asians and Pacific Islanders.

The Core Food Security Measure (CFSM) is used nationally to assess the extent and severity of household food insecurity in the previous 12 mo due to inadequate money for food. Both a scale measure and a categorical measure were developed from a national cross-sectional sample. The objective of this research was to determine whether the CFSM scale measure is a reliable and valid food security measure for use in Hawaii, where at least 50% of the population is of Asian or Pacific Islander descent. We completed an independent assessment of the robustness of the internal scale construct validity of the CSFM scale measure and hierarchical order of items using the same Rasch methods used previously to develop the CSFM. From a sample of 1664 respondents, data from 362 were used in the Rasch analysis. Item goodness-of-fit statistics indicated that responses to the "adults cut the size or skip meals" item and its follow-up item were redundant [outfit mean-square residual (MnSq) = 0.6, z = -2]. Responses to the "(un)able to eat balanced meals" item were erratic (outfit MnSq = 2.1, z = 2). Findings pertaining to goodness-of-fit of the respondents indicated an acceptable rate of misfit (4.7%). Rate of misfit did not vary with family status or with any ethnic group except the Samoans. Overall, the CFSM scale measure fit as well with the Hawaii data as it did with national data, although identified limitations may affect food security monitoring and research.

Adult↗