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Biomedical subjects

Richard E Harris

Publications and source records attributed to Richard E Harris.

At least 19 recordsLinked to original sources
PubMed2007

Chemotherapy for myeloid malignancy in children with Fanconi anemia.

BACKGROUND: Children with Fanconi anemia (FA) have a markedly increased risk of developing myeloid malignancies. Historically, patients with FA and myeloid malignancy have extremely poor outcomes. There are currently no clinical trials or case series addressing the use of chemotherapy for children with FA, except in the context of preparative regimens for stem cell transplantation (SCT). In this report we describe the toxicity of a chemotherapy approach for patients with FA and myeloid malignancy to achieve cytoreduction prior to SCT. PATIENTS AND METHODS: Four patients with FA and myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) were treated with chemotherapy (fludarabine 30 mg/m(2) and cytosine arabinoside 300 mg/m(2) each on days 2-4 and granulocyte-colony stimulating factor (G-CSF) 5 microg/kg on days 1-5), termed reduced intensity FLAG prior to SCT. RESULTS: The chemotherapy was well tolerated with expected hematologic toxicity and no measurable toxicity in other organs. Two of the three patients with AML cleared blasts from their bone marrow. Reduction in marrow cellularity was also achieved in one patient with hypercellular MDS. CONCLUSION: These data indicate that children with FA and myeloid malignancy can tolerate chemotherapy and achieve clearance of disease. It remains unclear whether pre-SCT chemotherapy improves currently poor survival rates for SCT in FA patients with myeloid malignancies and further studies are needed to determine if there is a clinical role for this strategy.

Acute Disease↗
PubMed2007

Favorable histology, MYCN-amplified 4S neonatal neuroblastoma.

We report a neonate with 4S neuroblastoma and MYCN amplification, but favorable Shimada histology, successfully treated with chemotherapy and 13-cis-retinoic acid without stem cell transplantation. MYCN amplification in neuroblastoma is usually associated with unfavorable Shimada histology; the presence of these features in infants with 4S disease confers a poor prognosis. A small number of infants with 4S neuroblastoma and MYCN amplification have favorable Shimada histology. In this subgroup of infants, histopathology may be equally important in predicting outcome.

Adrenal Gland Neoplasms↗
PubMed2006

Unrelated donor bone marrow transplantation for the treatment of Fanconi anemia.

Bone marrow transplantation (BMT) is the only known cure for the hematologic manifestations of Fanconi anemia (FA). Potential benefits of unrelated donor BMT for FA, however, have been severely limited by graft rejection and treatment-related mortality with resultant poor survival. Therefore, we evaluated the impact of potential prognostic factors on hematopoietic recovery, graft-versus-host disease (GVHD), and mortality in 98 recipients of unrelated donor BMT who received transplants between 1990 and 2003. Probabilities of neutrophil (89% vs 69%; P = .02) and platelet (74% vs 23%; P < .001) recovery were higher after fludarabine-containing regimens than nonfludarabine-containing regimens. Risks of acute GVHD (relative risk [RR], 4.29; P < .001) were higher with non-T-cell-depleted grafts. The day-100 mortality rate was significantly higher after nonfludarabine-containing regimens than fludarabine-containing regimens (65% vs 24%, respectively; P < .001). Corresponding 3-year adjusted overall survival rates were 13% versus 52% (P < .001). In addition, mortality was higher in recipients who were older (> 10 years), who were cytomegalovirus (CMV) seropositive, and who received more than 20 blood product transfusions before BMT. Based on these results, significant practice changes are suggested: use of a fludarabine-containing conditioning regimen in the context of T-cell-depleted marrow allografts, and earlier referral for transplantation prior to excessive transfusions in patients with marrow failure.

Acute Disease↗
PubMed2006

Cerebrospinal fluid corticotropin-releasing factor concentration is associated with pain but not fatigue symptoms in patients with fibromyalgia.

Previous studies have identified stress system dysregulation in fibromyalgia (FM) patients; such dysregulation may be involved in the generation and/or maintenance of pain and other symptoms. Corticotropin-releasing factor (CRF) is the principal known central nervous system mediator of the stress response; however, to date no studies have examined cerebrospinal fluid (CSF) CRF levels in patients with FM. The relationship between CSF CRF level, heart rate variability (HRV), and pain, fatigue, and depressive symptoms was examined in patients with FM. Among participants (n=26), CSF CRF levels were associated with sensory pain symptoms (r=0.574, p=0.003) and affective pain symptoms (r=0.497, p=0.011), but not fatigue symptoms. Increased HRV was also strongly associated with increased CSF CRF and FM pain. In multivariate analyses adjusting for age, sex, and depressive symptoms, the association between CSF CRF and sensory pain symptoms (t=2.54, p=0.027) persisted. Women with FM who reported a history of physical or sexual abuse had lower CSF CRF levels than women who did not report such a history. CSF CRF levels are associated with both pain symptoms and variation in autonomic function in FM. Differences in CSF CRF levels among women with and without a self-reported history of physical or sexual abuse suggest that subgroups of FM patients may exist with different neurobiological characteristics. Further studies are needed to better understand the nature of the association between CSF CRF and pain symptoms in FM.

Adrenal Cortex Hormones↗
PubMed2006

Bone marrow transplantation versus prolonged intensive chemotherapy for children with acute lymphoblastic leukemia and an initial bone marrow relapse within 12 months of the completion of primary therapy: Children's Oncology Group study CCG-1941.

PURPOSE: To compare conventional sibling bone marrow transplantation (CBMT), BMT with alternative donor (ABMT), and chemotherapy (CT) for children with acute lymphoblastic leukemia (ALL) and an early first marrow relapse. PATIENTS AND METHODS: After informed consent, 214 patients with ALL and early marrow relapse began multiagent induction therapy. One hundred sixty-three patients with fewer than 25% marrow blasts and count recovery at the end of induction (second remission [CR2]) were allocated by donor availability. Fifty patients with sibling donors were allocated to CBMT. Seventy-two patients were randomly allocated between ABMT and CT while 41 patients refused allocation. RESULTS: Overall, 3-year event free survival from entry is 19% +/- 3%. Thirty-two of 50 CBMT patients (64%) and 19 of 37 ABMT patients (51%) underwent transplantation in CR2 with 3-year disease-free survival of 42% +/- 7% and 29% +/- 7%. The 3-year DFS is 29% +/- 7%, 21% +/- 7%, and 27% +/- 8% for patients allocated to CBMT, ABMT, and CT, respectively. Contrary to protocol, 12 of 35 patients allocated to CT underwent BMT in CR2. Of these, five patients died after BMT and 5 patients relapsed. CONCLUSION: More than one half of patients died, failed reinduction, or relapsed again before 3 months after CR2 (median time to BMT). Intent-to-treat pair-wise comparison of ABMT with CT, CT with CBMT, and CBMT with ABMT yields hazards of 1.2, 1.1, 0.8 with P values of .56, .80, and .36, respectively. Outcomes remain similar and poor for children with ALL and early marrow relapse. BMT is not a complete answer to the challenge of ALL and early marrow relapse.

Adolescent↗
PubMed2006

Optimization of conditioning for marrow transplantation from unrelated donors for patients with aplastic anemia after failure of immunosuppressive therapy.

In 87 patients with aplastic anemia who failed to respond to immunosuppressive treatment, we determined the minimal dose of total body irradiation (TBI) required when added to antithymocyte globulin (ATG, 30 mg/kg x 3) plus cyclophosphamide (CY, 50 mg/kg x 4) to achieve engraftment of unrelated donor marrow. TBI was started at 3 x 200 cGy, to be escalated or deescalated in steps of 200 cGy depending on graft failure or toxicity. Patients were aged 1.3 to 53.5 years (median, 18.6 years). The interval from diagnosis to transplantation was 3 to 328 months (median, 14.6 months). Donors were HLA-A, -B, -C, -DR, and -DQ identical for 62 patients, and nonidentical for 1 to 3 HLA loci at the antigen or allele level for 25. The dose-limiting toxicity was diffuse pulmonary injury. The optimum TBI dose was 1 x 200 cGy. Nine patients did not tolerate ATG and were prepared with CY + TBI. Graft failure occurred in 5% of patients. With a median follow-up of 7 years, 38 (61%) of 62 HLA-identical, and 10 (40%) of 25 HLA-nonidentical transplant recipients are surviving. The highest survival rate with HLA-identical transplants was observed at 200 cGy TBI. Thus, low-dose TBI + CY + ATG conditioning resulted in excellent outcome of unrelated transplants in patients with aplastic anemia who had received multiple transfusions.

Adolescent↗
PubMed2006

Asparagine depletion after pegylated E. coli asparaginase treatment and induction outcome in children with acute lymphoblastic leukemia in first bone marrow relapse: a Children's Oncology Group study (CCG-1941).

PURPOSE: Re-induction outcomes vary for children with acute lymphoblastic leukemia (ALL) and marrow relapse. We explored possible relationships among asparaginase (ASNase) activity levels, asparagine (ASN) depletion, anti-ASNase antibody titers, and response to re-induction therapy in children and adolescents with ALL and an 'early' first marrow relapse. PATIENTS AND METHODS: After appropriate informed consent, we enrolled children and adolescents 1-21 years old with ALL and first marrow relapse within 12 months of completion of primary therapy. Induction therapy included intramuscular pegylated ASNase on Days 2 and 16. We assessed ASNase activity, anti-ASNase antibody titers against native and pegylated (E. coli) ASNase, and amino acid levels of asparagine (ASN) and glutamine (GLN) on Days 0, 14, and 35 of re-induction. RESULTS: Ninety-three patients were at least partially assessable. Among 21 patients with M1 marrow status at Day 35, the median Day 14 ASN level was <1 microM. This is significantly lower than the median Day 14 ASN level of 4 microM in the group of patients with M3 marrow at Day 35. Neither Day 0 nor Day 35 antibody titers predicted ASNase enzymatic activity level on Day 14. Surprisingly, Day 14 ASNase activity did not predict serum ASN level on Day 14. However, Day 0 and Day 35 anti-native ASNase antibody titers, and Day 0 anti-PEG ASNase antibody titers correlated positively with Day 14 serum ASN levels as one might expect from neutralizing antibody. Day 35 anti-PEG ASNase antibody titers did not. CONCLUSIONS: Patients with greater ASN depletion were more likely to achieve second remission in the context of six-drug therapy.

Antibody Formation↗
PubMed2006

How do we know that the pain in fibromyalgia is "real"?

Fibromyalgia is a common idiopathic pain condition often resulting in increased morbidity and disability in patients. The lack of peripheral abnormalities in this disease has led clinicians and researchers alike to question if this syndrome represents a valid entity. Recent genetic findings suggest that specific gene mutations may predispose individuals to develop fibromyalgia. In addition, neurobiological studies indicate that fibromyalgia patients have abnormalities within central brain structures that normally encode pain sensations in healthy pain-free controls. Future studies that focus on central neurobiological and/or genetic influences in fibromyalgia may bring insight into mechanisms of this problematic disease and ultimately result in improved treatments.

Central Nervous System↗
PubMed2006

Comparison of clinical and evoked pain measures in fibromyalgia.

UNLABELLED: Evoked pain measures such as tender point count and dolorimetry are often used to determine tenderness in studies of fibromyalgia (FM). However, these measures frequently do not improve in clinical trials and are known to be influenced by factors other than pain such as distress and expectancy. The purpose of this investigation was to determine whether evoked pain paradigms that present pressure stimuli in a random fashion (eg, Multiple Random Staircase [MRS]) would track with clinical pain improvement in patients with FM better than traditional measures. Sixty-five subjects enrolled in a randomized clinical trial of acupuncture were observed longitudinally. Clinical pain was measured on a 101-point numerical rating scale (NRS) and the Short Form McGill Pain Questionnaire (SF-MPQ), whereas evoked pressure sensitivity was assessed via manual tender point count, dolorimetry, and MRS methods. Improvements in clinical pain and evoked pain were assessed irrespective of group assignment. Improvement was seen in clinical pain during the course of the trial as measured by both NRS (P = .032) and SF-MPQ (P = .001). The MRS was the only evoked pain measure to improve correspondingly with treatment (MRS, P = .001; tender point count and dolorimeter, P > .05). MRS change scores were correlated with changes in NRS pain ratings (P = .003); however, this association was not stronger than tender point or dolorimetry correlations with clinical pain improvement (P > .05). Pain sensitivity as assessed by random paradigms was associated with improvements in clinical FM pain. Sophisticated pain testing paradigms might be responsive to change in clinical trials. PERSPECTIVE: Trials in fibromyalgia often use both clinical and experimental methods of pain assessment; however, these two outcomes are often poorly correlated. We explore the relationship between changes in clinical and experimental pain within FM patients. Pressure pain testing that applies stimuli in a random order is associated with improvements in clinical pain, but this association was not stronger than other experimental techniques.

Acupuncture Analgesia↗
PubMed2006

Policy for therapeutic acupuncture in an academic health center: a model for standard policy development.

Acupuncture as a therapeutic modality offers multiple applications. Its effectiveness coupled with its general acceptance by conventional health care professionals makes it one of the first complementary and alternative medicine (CAM) modalities to be incorporated in an integrative approach to care. However, few centers that offer acupuncture have written standard policies to regulate its use. This lack of standard policies may impede provision of quality care, serve as a barrier to cross-institutional data collection and clinical application of that data, and may put health care professionals and institutions at risk when credentialing or malpractice liability has not been clearly addressed. Here we present a policy for acupuncture, created by a diverse group of health care professionals at the University of Michigan Health System. It may function as a generalizable template for standard policy development by institutions incorporating acupuncture.

Academic Medical Centers↗
PubMed2005

Momentary relationship between cortisol secretion and symptoms in patients with fibromyalgia.

OBJECTIVE: To compare the momentary association between salivary cortisol levels and pain, fatigue, and stress symptoms in patients with fibromyalgia (FM), and to compare diurnal cycles of cortisol secretion in patients with FM and healthy control subjects in a naturalistic environment. METHODS: Twenty-eight patients with FM and 27 healthy control subjects completed assessments on salivary cortisol levels and pain, fatigue, and stress symptoms, 5 times a day for 2 consecutive days, while engaging in usual daily activities. Only those participants who adhered to the protocol (assessed via activity monitor) were included in the final analyses. RESULTS: Twenty FM patients and 16 healthy control subjects adhered to the protocol. There were no significant differences in cortisol levels or diurnal cortisol variation between FM patients and healthy controls. Among women with FM, a strong relationship between cortisol level and current pain symptoms was observed at the waking time point (t = 3.35, P = 0.008) and 1 hour after waking (t = 2.97, P = 0.011), but not at the later 3 time points. This association was not due to differences in age, number of symptoms of depression, or self-reported history of physical or sexual abuse. Cortisol levels alone explained 38% and 14% of the variation in pain at the waking and 1 hour time points, respectively. No relationship was observed between cortisol level and fatigue or stress symptoms at any of the 5 time points. CONCLUSION: Among women with FM, pain symptoms early in the day are associated with variations in function of the hypothalamic-pituitary-adrenal axis.

Adult↗
PubMed2005

Characterization and consequences of pain variability in individuals with fibromyalgia.

OBJECTIVE: A growing body of evidence suggests that real-time electronic assessments of pain are preferable to traditional paper-and-pencil measures. We used electronic assessment data derived from a study of patients with fibromyalgia (FM) to examine variability of pain over time and to investigate the implications of pain fluctuation in the context of a clinical trial. METHODS: The study group comprised 125 patients with FM who were enrolled in a randomized, placebo-controlled trial of milnacipran. Pain intensity levels were captured in real time by participants using electronic diaries. Variability in pain was assessed as the standard deviation of pain entries over time (pain variability index [PVI]). RESULTS: Substantial between-subject differences in pain variability were observed (mean +/- SD PVI 1.61 +/- 0.656 [range 0.27-4.05]). The fluctuation in pain report was constant over time within individuals (r = 0.664, P < 0.001). Individuals with greater variability were more likely to be classified as responders in a drug trial (odds ratio 6.14, P = 0.006); however, this association was primarily attributable to a greater change in pain scores in individuals receiving placebo (r = 0.460, P = 0.02) rather than active drug (r = 0.09, P > 0.10). CONCLUSION: Among individuals with FM, there were large between-subject differences in real-time pain reports. Pain variability was relatively constant over time within individuals. Perhaps the most important finding is that individuals with larger pain fluctuations were more likely to respond to placebo. It is not clear whether these findings are applicable only to patients with FM or whether they may also be seen in patients with other chronic pain conditions.

Cyclopropanes↗
PubMed2005

Differences in unpleasantness induced by experimental pressure pain between patients with fibromyalgia and healthy controls.

Pain possesses both sensory and affective dimensions, which are highly correlated yet distinct. Comparison of these dimensions within experimental pain settings has resulted in the construct of relative unpleasantness. Relative unpleasantness is defined as the amount of affective unpleasantness elicited for a given sensory magnitude. The aim of this study was to determine the relationship between affective and sensory components of evoked pain in subjects with fibromyalgia (FM) and healthy controls. Here we show that patients with FM unexpectedly display less relative unpleasantness than healthy controls in response to random noxious pressure stimuli. Relative unpleasantness was not correlated with distress, anxiety, or depression, which were pronounced in the FM group. Clinical pain in patients with FM was perceived to be more unpleasant than the evoked pain stimuli. These results are consistent with the concept that chronic pain may reduce the relative unpleasantness of evoked pain sensations.

Adult↗
PubMed2005

Treatment of fibromyalgia with formula acupuncture: investigation of needle placement, needle stimulation, and treatment frequency.

OBJECTIVES: The objective of this study was to investigate whether typical acupuncture methods such as needle placement, needle stimulation, and treatment frequency were important factors in fibromyalgia symptom improvement. DESIGN/SETTINGS/SUBJECTS: A single-site, single-blind, randomized trial of 114 participants diagnosed with fibromyalgia for at least 1 year was performed. INTERVENTION: Participants were randomized to one of four treatment groups: (1) T/S needles placed in traditional sites with manual needle stimulation (n = 29): (2) T/0 traditional needle location without stimulation (n = 30); (3) N/S needles inserted in nontraditional locations that were not thought to be acupuncture sites, with stimulation (n = 28); and (4) N/0 nontraditional needle location without stimulation (n = 2 7). All groups received treatment once weekly, followed by twice weekly, and finally three times weekly, for a total of 18 treatments. Each increase in frequency was separated by a 2-week washout period. OUTCOME MEASURES: Pain was assessed by a numerical rating scale, fatigue by the Multi-dimensional Fatigue Inventory, and physical function by the Short Form-36. RESULTS: Overall pain improvement was noted with 25%-35% of subjects having a clinically significant decrease in pain; however this was not dependent upon "correct" needle stimulation (t = 1.03; p = 0.307) or location (t = 0.76; p = 0.450). An overall dose effect of treatment was observed, with three sessions weekly providing more analgesia than sessions once weekly (t = 2.10; p = 0.039). Among treatment responders, improvements in pain, fatigue, and physical function were highly codependent (all p < or = 0.002). CONCLUSIONS: Although needle insertion led to analgesia and improvement in other somatic symptoms, correct needle location and stimulation were not crucial.

Acupuncture Analgesia↗
PubMed2005

Using acupressure to modify alertness in the classroom: a single-blinded, randomized, cross-over trial.

BACKGROUND: Previous reports have suggested that acupressure is effective in reducing pain and improving sleep quality; however, its effects on alertness have not been characterized. OBJECTIVES: The aim of this study was to determine whether two different acupressure treatments have opposing effects on alertness in a full-day classroom setting. DESIGN: This was a cross-over (two-treatments; three periods), single-blinded, randomized trial. SETTING: The University of Michigan School of Public Health was the setting. SUBJECTS: Students attending a course in clinical research design and statistical analysis at the University of Michigan participated in the study. INTERVENTIONS AND OUTCOME MEASURES: Blinded subjects were randomized to two acupressure treatment sequences: stimulation-relaxation-relaxation or relaxation-stimulation-stimulation. Acupressure treatments were self administered over 3 consecutive days. Pre- and post-treatment alertness scores were assessed each day using the Stanford Sleepiness Scale (SSS). Changes in the SSS score (afternoon-morning) were analyzed using a mixed regression model of fixed and random effects. Important factors that were expected to affect alertness, such as caffeine and previous night's sleep, were also assessed. RESULTS: Baseline characteristics and protocol compliance were similar between the two sequences. Stimulation acupressure treatment yielded a 0.56-point greater difference in score on the SSS, corresponding to less fatigue, compared to the relaxation acupressure treatment (p = 0.019). Day of study (p = 0.004) and hours of overnight sleep (p = 0.042) also significantly affected the change in SSS scores. Incorporating participants' beliefs as to which treatment they received did not significantly alter the observed treatment effect. CONCLUSIONS: Acupressure at stimulation and relaxation points has differential effects on alertness in a classroom setting. Further research is necessary to confirm these findings and to determine whether stimulation and relaxation acupressure are equally effective in influencing alertness.

Acupressure↗
PubMed2004

Comparison of graft-versus-host-disease and survival after HLA-identical sibling bone marrow transplantation in ethnic populations.

The association of ethnicity with the incidence of graft-versus-host disease (GVHD) and other clinical outcomes after transplantation is controversial. We compared the results of HLA-identical sibling bone marrow transplantations for leukemia, performed between 1990 and 1999, among different ethnic populations, including 562 Japanese, 829 white Americans, 71 African Americans, 195 Scandinavians, and 95 Irish. Results for adults and children were analyzed separately. Multivariate analyses of adult patients showed that white Americans, African Americans, and Irish cohorts were at significantly higher risk for acute GVHD than Japanese or Scandinavian cohorts (relative risk [RR] = 1.77, P < .001; RR = 1.84, P < .006; RR = 2.22, P < .001, respectively). White Americans, African Americans, and Irish, but not Scandinavians, were at significantly higher risk for early (within 3 months of transplantation) transplant-related mortality (TRM) compared with Japanese (RR = 2.99, P < .001; RR = 5.88, P < .001; RR = 2.66, P < .009, respectively). No differences in the risk for chronic GVHD, relapse, and overall survival were noted. In the pediatric cohort (limited to Japanese and white Americans), white Americans were at significantly higher risk for acute (RR = 1.93; P = .04) and chronic (RR = 3.16; P = .002) GVHD. No differences in other clinical outcomes were noted. Our findings suggest that ethnicity may influence the risk for GVHD, though overall survival rates after transplantation remain similar.

Adult↗