Search PubMed⌕ Search

Biomedical subjects

K B Miller

Publications and source records attributed to K B Miller.

At least 19 recordsLinked to original sources

A prospective, randomized trial for the prevention of mucositis in patients undergoing hematopoietic stem cell transplantation.

Oral mucositis is a complication common to many cancer therapies and produces considerable pain and morbidity. The present study reports a double-blind, prospective, randomized clinical trial testing the efficacy of a calcium phosphate mouth rinse (Caphosol) with fluoride treatments vs a standard regimen of fluoride rinsing and placebo tray treatments in 95 patients undergoing hematopoietic stem cell transplantation (HSCT). The days and severity of mucositis were prospectively evaluated. There were statistically significant decreases in days of mucositis (3.72 vs 7.22 P=0.001), duration of pain (2.86 vs 7.67, P=0.0001), dose of morphine (34.54 mg vs 122.78 mg), days of morphine (1.26 vs 4.02, P=0.0001) and days to the onset of engraftment ANC (absolute neurotrophil count)>200 mm(3) (11.12 vs 12.56) in the Caphosol and fluoride treatment group vs fluoride-rinse group, respectively. Caphosol, a neutral, supersaturated, Ca(2+)/PO(4)(3-) mouth rinse, used in combination with topical fluoride treatments, is superior to fluoride rinse alone in reducing the frequency, intensity and duration of oral mucositis in patients undergoing HSCT.

Analysis of Variance↗

Extracorporeal photopheresis in chronic graft-versus-host disease.

Despite significant advances in stem cell manipulation and post-transplant immunosuppression, chronic graft-versus-host disease (cGVHD) remains a cause of major long-term morbidity in survivors of allogeneic stem cell transplantation. Extracorporeal photopheresis (ECP) is a novel therapeutic intervention which has demonstrated efficacy in patients with refractory acute and chronic GVHD. Clinical responses have been reported in skin and visceral GVHD. While the long-term immunomodulatory effects of ECP in cGVHD are unknown, recent studies of patients undergoing a 6- to 12-month course of ECP treatment demonstrated an attenuation of Th1-mediated cytokine secretion by activated T-helper cells, a shift in the DC1/DC2 ratio favoring plasmacytoid rather than monocytoid dendritic cell profiles, and a decrease in antigen responsiveness by dendritic cells. The implications of these immunomodulatory effects of ECP on pathogenesis and clinical outcome remains a fertile area for future research.

Bone Marrow Transplantation↗

Randomized trial of filgrastim versus chemotherapy and filgrastim mobilization of hematopoietic progenitor cells for rescue in autologous transplantation.

Peripheral blood cell (PBC) rescue has become the mainstay for autologous transplantation in patients with lymphoma, multiple myeloma, and solid tumors. Different methods of hematopoietic progenitor cell (HPC) mobilization are in use without an established standard. Forty-seven patients with relapsed or refractory lymphoma received salvage chemotherapy and were randomized to have HPC mobilization using filgrastim [granulocyte-colony-stimulating factor (G-CSF)] alone for 4 days at 10 microg/kg per day (arm A) or cyclophosphamide (5 g/m(2)) and G-CSF at 10 microg/kg per day until hematologic recovery (arm B). Engraftment and ease of PBC collection were primary outcomes. All patients underwent the same high-dose chemotherapy followed by reinfusion of PBCs. There were no differences in median time to neutrophil engraftment (11 days in both arms; P =.5) or platelet engraftment (14 days in arm A, 13 days in arm B; P =.35). Combined chemotherapy and G-CSF resulted in higher CD34(+) cell collection than G-CSF alone (median, 7.2 vs 2.5 x 10(6) cells/kg; P =.004), but this did not impact engraftment. No differences were found in other PBC harvest outcomes or resource utilization measures. A high degree of tumor contamination, as studied by consensus CDR3 polymerase chain reaction of the mobilized PBCs, was present in both arms (92% in arm A vs 90% in arm B; P = 1). No differences were found in overall survival or progression-free survival at a median follow-up of 21 months. This randomized trial provides clinical evidence that the use of G-CSF alone is adequate for HPC mobilization, even in heavily pretreated patients with relapsed lymphoma.

Adult↗

Immunomodulatory effects of extracorporeal photochemotherapy in patients with extensive chronic graft-versus-host disease.

Extracorporeal photochemotherapy (ECP) has been associated with clinical improvement in several patients with acute and chronic graft-versus-host disease (cGVHD) after allogeneic bone marrow transplantation, but the mechanism of action is unknown. This study tested the hypothesis that in patients with cGVHD, ECP modulates alloreactivity by affecting activated lymphocyte populations or by altering the interaction between effector lymphocytes and antigen-presenting cells (APCs). Ten patients who had refractory cGVHD were treated with ECP, and the clinical response to and immunologic effects of this therapy were assessed. Seven patients had a response and 3 had no change in clinical manifestations of cGVHD. One patient died from catheter-related sepsis. Immunologic effects observed after ECP included normalization of inverted ratios of CD4 to CD8 cells, an increase in the number of CD3-CD56+ natural killer (NK) cells, and a decrease in CD80+ and CD123+ circulating dendritic cells. The results suggest that ECP modulates both NK cells and APC populations in patients with cGVHD.

Adult↗

Phase II study of combination human recombinant GM-CSF with intermediate-dose cytarabine and mitoxantrone chemotherapy in patients with high-risk myelodysplastic syndromes (RAEB, RAEBT, and CMML): an Eastern Cooperative Oncology Group Study.

A Phase II study of GM-CSF with intermediate-dose cytarabine and mitoxantrone was conducted in patients with high-risk myelodysplastic syndrome. It was designed to evaluate if priming with growth factor could increase the efficiency of chemotherapy. In this older population only two of 10 patients achieved a bone marrow CR, including one patient whose leukemic blasts had an "S" phase increase of 2.55x at 48 hr. Unexpected hepatotoxicity was noted. This regimen cannot be recommended for this elderly population of patients.

Aged↗

Genetic and environmental influences on anorexia nervosa syndromes in a population-based twin sample.

BACKGROUND: Genetic and environmental influences on broadly-defined anorexia nervosa (AN) syndrome were examined in a population-based twin sample. METHODS: AN syndrome was assessed in 672 female 17 year-old twins using structured interviews and a self-report questionnaire. RESULTS: Twenty-six probands with AN syndrome were identified. Biometrical model-fitting analyses indicated that genetic and non-shared environmental factors accounted for 74% and 26% of the variance in AN syndrome, respectively. CONCLUSIONS: Findings support previous research indicating significant genetic and non-shared environmental influences on AN syndromes.

Adolescent↗

A multicenter, randomized, double-blind comparison of different doses of intravenous immunoglobulin for prevention of graft-versus-host disease and infection after allogeneic bone marrow transplantation.

Intravenous immunoglobulin is approved for use in allogeneic bone marrow transplant recipients for prevention of graft-versus-host disease (GVHD) and infections, but the minimally effective dose has not been established. In this multicenter, randomized, double-blind trial, patients undergoing allogeneic marrow transplantation were randomized to receive 100 mg/kg, 250 mg/kg, or 500 mg/kg doses of intravenous immunoglobulin. Each dose was given weekly for 90 days and then monthly until 1 year after transplant. Six hundred and eighteen patients were evaluated. Acute GVHD (grades 2-4) occurred in 39% of the patients (80 of 206) in the 100 mg/kg group, 42% of the patients (88 of 208) in the 250 mg/kg group, and in 35% of the patients (72 of 204) in the 500 mg/kg group (P = 0.344). Among patients with unrelated marrow donors, a higher dose of intravenous immunoglobulin (500 mg/kg) was associated with less acute GVHD (P = 0.07). The incidences of chronic GVHD, infection and interstitial pneumonia were similar for all three doses of intravenous immunoglobulin. The dose of intravenous immunoglobulin also had no effect on the types of infection, relapse of hematological malignancy or survival. Except for more frequent chills (P = 0.007) and headaches (P = 0.015) in patients given the 500 mg/kg or 250 mg/kg dose of immunoglobulin, adverse events were similar for all three doses. These results suggest that 100 mg/kg, 250 mg/kg, and 500 mg/kg doses of intravenous immunoglobulin are associated with similar incidences of GVHD and infections in most allogeneic marrow transplants. These results should be considered when designing cost-effective strategies for the use of intravenous immunoglobulin in allogeneic marrow transplants receiving other current regimens for prophylaxis of GVHD and infection.

Adolescent↗

Social adjustment over 10 years following diagnosis with bulimia nervosa.

OBJECTIVE: The authors sought to describe social adjustment among women diagnosed with bulimia nervosa more than a decade earlier. METHOD: A cohort of women who were diagnosed with bulimia nervosa between 1981 and 1987 were located and invited to participate in follow-up assessments. RESULTS: Although the current sample demonstrated considerable improvement in disordered eating behaviors and social adjustment, measures of social adjustment suggested continued impairment in interpersonal relationships and only a modest association with eating disorder outcome. DISCUSSION: Continued difficulties in social adjustment may reflect an underlying vulnerability from which disordered eating developed. Treatments for bulimia nervosa may benefit from including interpersonal skills training.

Adult↗

Myelodysplastic syndromes.

Myelodysplastic syndromes (MDS) are a heterogeneous group of disorders with a variable clinical course and prognosis. Treatment should be individualized based on the patient's age, subtype, percent blasts in the marrow, and cytogenetics. The use of the International Prognostic Scoring Index is helpful in assigning prognosis. The standard of care for low-risk patients is supportive care. Low-risk patients with symptomatic anemia should be considered for a trial of erythropoietin. The serum erythropoietin (EPO) level may help predict response to treatment. The treatment of the symptomatic and high-risk patient is unclear. Low-dose cytarabine, amifostine, and 5-azacitidine can induce responses in selected patients, but the duration of responses is short, and treatment does not appear to prolong survival. Intensive chemotherapy should be reserved for high-risk, younger patients. Topotecan and intermediate cytarabine appear to have an active regimen, but remissions are short. Younger patients who present with high-risk MDS without an antecedent history of MDS should receive intensive acute myeloid leukemia (AML) induction chemotherapy. Younger patients with high-risk MDS and an HLA-compatible donor should be offered an allogeneic stem cell transplant.

Age Factors↗

Treatment of primary resistant or relapsed multiple myeloma with high-dose chemoradiotherapy, hematopoietic stem cell rescue, and granulocyte-macrophage colony-stimulating factor.

In this prospective, multicenter, phase 2 study, multiple myeloma (MM) patients with primary resistant disease or recurrent chemosensitive disease, in chemoresistant relapse, or in second or subsequent remission were treated with high-dose chemoradiotherapy followed by autologous peripheral blood stem cell (PBSC) rescue. PBSCs were collected using granulocyte-macrophage colony-stimulating factor (GM-CSF) 5 microg/kg per day subcutaneously for 3 days. Patients underwent high-dose chemoradiotherapy consisting of melphalan (140 mg/m2 x 1 day), cyclophosphamide (60 mg/kg per day x 2 days), methylprednisolone (2 g/d x 7 days), and total body radiation (150 cGy bid x 3 days) followed by peripheral blood stem cell reinfusion (> or = 1.2 x 10(9) mononucleated cells per kg) and GM-CSF support (5 microg/kg per day) and were evaluated for response, survival, and toxicity. Thirty-six patients, median age 53.4 years, completed the study. The mean pretransplantation cumulative melphalan dose was 464 +/- 72 mg. Excluding the 3 patients (8.3%) who failed to engraft, the median times to engraftment and platelet recovery were 10 days (range, 8-39 days) and 17 days (range, 7-67 days), respectively. Four patients (11.1%) died of complications related to the regimen (main causes of death, sepsis and acute respiratory distress syndrome) within the first 100 days. Twenty-two patients (61.1%) achieved complete response (CR), 8 (22.2%) partial response, and 2 (5.5%) no response. Two patients developed myelodysplastic syndrome after achieving CR. For all 36 patients, the probability of overall survival at 5 years was 27.3%. Median survival was 31 months (range, 0.3-81 months) in all patients and 42 months (range, 3.4-81 months) in those with CR. The probabilities of overall and disease-free survival at 5 years for the 22 patients who achieved CR were 43.6% and 15.7%, respectively. This high-dose chemotherapy regimen coupled with PBSC rescue is associated with a high CR rate and is capable of inducing long-term survival in a subset of heavily pretreated patients with primary resistant or recurrent MM.

Adolescent↗

Varicella zoster virus infections following allogeneic bone marrow transplantation: frequency, risk factors, and clinical outcome.

Reactivation of varicella zoster virus (VZV) is a common event in patients undergoing allogeneic bone marrow transplantation (BMT) and may lead to life-threatening complications. We retrospectively analyzed the incidence, clinical outcome, and risk factors for VZV infections occurring within the first 5 years of transplantation in 100 consecutive adults undergoing allogeneic BMT between 1992 and 1997. Forty-one patients (41%) developed VZV reactivation a median of 227 days (range 45-346 days) post-transplantation. Twelve percent of VZV reactivation occurred in the first 100 days and 88% within the first 24 months. Among those who survived for 2 or more years after transplantation (n = 47), 59% developed VZV infection. Forty percent of patients with VZV reactivation required admission with a mean hospital stay of 7.2 days. Two patients developed encephalitis, and 1 died despite antiviral therapy. The most frequent complications were post-herpetic neuralgia and peripheral neuropathy (68%). Thoracic dermatomal zoster represented 41% of the infections; disseminated cutaneous involvement was observed in 17% of patients. No clinical or epidemiologic risk factors were associated with recurrence. Administration of ganciclovir for prevention of cytomegalovirus infection delayed the onset of VZV infection beyond 4 months (P = .06). In a further subset analysis, patients with a limited chronic graft-versus-host disease (GVHD) had a lower estimated incidence of VZV reactivation compared with those with extensive chronic GVHD (P = .11). We conclude that complications from reactivation of VZV infection are common and associated with considerable morbidity and mortality in patients undergoing allogeneic BMT.

2-Aminopurine↗

High dietary manganese lowers heart magnesium in pigs fed a low-magnesium diet.

Young pigs were fed a diet moderately high or low in manganese (Mn) (0.95 +/- 0.10 mmol Mn/kg, n = 8 or 0.040 +/- 0.003 mmol Mn/kg, n = 6) and deficient in magnesium (Mg) (4.1 mmol Mg/kg) for 5 wk. All eight pigs consuming the high Mn diet died following convulsive seizures, whereas only two of six died in the group fed low Mn. In an attempt to determine the cause of death, a subsequent study examined the interactive effect of deficient dietary Mg and Mn on the tissue distribution of Mg and Mn. Pigs were individually fed, for 5 wk, diets that contained: 4.1 mmol Mg/kg and 36.0 micromol Mn/kg, 4.1 mmol Mg/kg and 0.91 mmol Mn/kg, 4.1 mmol Mg/kg and 0.91 mmol Mn/kg with added ultratrace minerals, or 41.1 mmol Mg/kg and 0. 91 mmol Mn/kg, and ultratrace minerals. Liver and skeletal muscle Mn concentrations were significantly elevated by increased dietary Mn. Increased dietary Mn did not affect heart Mn, but heart Mg concentrations were significantly depressed by high, as compared to low, dietary Mn (38.7 +/- 3.3 vs. 32.7 +/- 2.6 mmol Mg/kg). These data suggest high dietary Mn may exacerbate Mg deficiency in heart muscle and thus may be a complicating factor in the deaths observed in Mg-deficient pigs.

Animals↗

Predictive validity of bulimia nervosa as a diagnostic category.

OBJECTIVE: The authors sought to investigate the predictive validity of bulimia nervosa as a diagnostic category. METHOD: More than 10 years after they appeared as patients with bulimia nervosa, 177 women (participation rate=79.7%) completed follow-up assessments. RESULTS: Among the women with a current eating pathology, most engaged in recurrent binge eating and purging. Anorexia nervosa and binge eating disorder were relatively uncommon. Eating disorder outcome was significantly related to the presence of mood, substance use, and impulse control disorders but not to the presence of anxiety disorders. CONCLUSIONS: These results support the validity of bulimia nervosa as a diagnostic category that is distinct from anorexia nervosa. Furthermore, these results suggest that bulimic symptoms are associated with disorders involving distress and disinhibition.

Anorexia Nervosa↗

Extramedullary tumors of myeloid blasts in adults as a pattern of relapse following allogeneic bone marrow transplantation.

BACKGROUND: Extramedullary tumors of lymphoid and myeloid blasts outside the well-defined sanctuaries following allogeneic bone marrow transplantation (allo-BMT) are rare. Little is known about the biology, treatment, and outcome of these tumors in this setting. METHODS: In this retrospective analysis, 134 consecutive patients with acute myeloid leukemia (AML) or chronic myeloid leukemia (CML) who underwent allo-BMT at a single institution between 1990 and 1998 were reviewed. Five cases of isolated extramedullary myeloid sarcoma that occurred as patterns of recurrence following allo-BMT between 1990 and 1998 are reported. These patients were treated with radiotherapy, systemic chemotherapy, or a second allo-BMT. Clinical outcome is compared with posttransplantation bone marrow relapses observed during the same period at the same institution. The literature on the clinical characteristics, currently available treatment, and outcome of posttransplantation myeloid sarcoma patients was reviewed. RESULTS: Excluding isolated skin and central nervous system recurrences, the frequency of extramedullary myeloid sarcoma encountered as a relapse pattern following allo-BMT was determined to be 3.7% among patients with acute or chronic leukemia of myeloid origin. The survival of patients who were managed with radiotherapy and systemic chemotherapy was less than 4 months. A patient who underwent a second allo-BMT following local radiotherapy is alive and in complete remission more than 33 months after the diagnosis of myeloid sarcoma. The median survival of 17 patients with posttransplantation bone marrow relapse following allo-BMT was 2.2 months. When posttransplantation medullary recurrences are analyzed, patients with CML had a median survival of 12 months, with a significantly better 5-year survival rate than patients with AML (0 vs. 60%, P = 0.015; median survival, 12 months). CONCLUSIONS: The clinical outcomes of patients with recurrent isolated extramedullary myeloid sarcoma following allo-BMT are poor, as in any leukemic relapse, with the exception of patients with CML in this setting.

Adult↗

Long-term outcome of bulimia nervosa.

BACKGROUND: Since bulimia nervosa's introduction to the psychiatric nomenclature in 1979, data concerning long-term outcome have been largely unavailable. METHODS: Women with the diagnosis of bulimia nervosa between 1981 and 1987 who participated in 1 of 2 studies were located and invited to participate in follow-up assessments. RESULTS: More than 80% of the women from these studies participated in follow-up assessments and the results represent findings for 173 women. More than 10 years following presentation (mean+/-SD length of follow-up, 11.5+/-1.9 years), 11% of this sample met full criteria for bulimia nervosa, and 0.6% met full criteria for anorexia nervosa. An additional 18.5% met criteria for eating disorder not otherwise specified, and 69.90% of this sample were either in full or in partial remission. For predictive factors, only the duration of the disorder at presentation and history of substance use problems demonstrated prognostic significance. Baseline treatment condition was not associated with remission of disordered eating symptoms by the follow-up assessment. CONCLUSIONS: The findings suggest that the number of women who continue to meet full criteria for bulimia nervosa declines as the duration of follow-up increases; approximately 30%, however, continued to engage in recurrent binge eating or purging behaviors (incidence rate, 0.026 cases per person-years). A history of substance use problems and a longer duration of the disorder at presentation predicted worse outcome.

Adult↗

The association of interleukin 6 with clinical and laboratory parameters of acute pelvic inflammatory disease.

OBJECTIVE: We sought (1) to determine whether interleukin 6 levels are increased in plasma and cervical secretions and endometrial tissue obtained from women with a clinical diagnosis of pelvic inflammatory disease, (2) to determine whether interleukin 6 levels in these sample sites reflected the clinical severity of acute infection, and (3) to determine whether interleukin 6 levels in endometrial tissue obtained from these women were higher in the presence of histologic endometritis. STUDY DESIGN: We performed a prospective pilot study on 20 women with a clinical diagnosis of pelvic inflammatory disease (patients) and then compared them with 20 women presenting to the gynecology clinic without pelvic complaints (control subjects). Interleukin 6 levels were measured by enzyme-linked immunologic testing in plasma, cervical secretions, and endometrial biopsy specimens. RESULTS: Cervical interleukin 6 levels were higher in patients than control subjects (median, 317 vs 111 pg/mL; P =.003). Among women with pelvic inflammatory disease, statistically significant positive correlations were noted between the clinical severity score and the erythrocyte sedimentation rate (r = 0.45; P =.04), the clinical severity score and the white blood cell count (r = 0.49; P =.03), the plasma interleukin 6 levels and the erythrocyte sedimentation rate (r = 0.55; P =.02), and the plasma interleukin 6 levels and the white blood cell count (r = 0.54, P =.01). Endometrial tissue interleukin 6 levels were also higher in patients with versus those without histologic endometritis (median, 427 vs 17 pg/mL; P =.004). CONCLUSION: In this pilot study interleukin 6 levels in cervical secretions were significantly higher in women with pelvic inflammatory disease versus those without pelvic inflammatory disease. In women with pelvic inflammatory disease, endometrial tissue samples with histologic evidence of endometritis were observed to have higher levels of interleukin 6. Interleukin 6 may be a useful adjunct to the clinical diagnosis of pelvic inflammatory disease.

Acute Disease↗

Catastrophic hemorrhage on sternal reentry: still a dreaded complication?

BACKGROUND: To define the incidence of catastrophic hemorrhage (CH) during reoperations, the experience of the University of New Mexico was reviewed and compared with the practice of surgeons contacted by questionnaire. METHODS: At the University of New Mexico, 610 reoperations were reviewed and 210 deemed high risk because of multiple reoperation, aneurysm, patent grafts, chamber's enlargement, conduit or previous mediastinitis. In the questionnaire, we asked about reentry technique, occurrence and outcome of CH, and precautions for high-risk patients. RESULTS: At the University of New Mexico there were 4 CH with 1 death, and in the questionnaire there were 2,046 CH with 392 deaths. Our rate per surgeon was lower than that of the questionnaire. Rate of CH according to the saw was 2.09 for reciprocating, 2.0 for sagittal, and 1.74 for stryker in the questionnaire. Our rate was lower (0.65) with a micro sagittal saw. High-risk category predicted CH during sternotomy (p = 0.01) but only conduit (p = 0.005) was significant by univariate analysis. CONCLUSIONS: The risk of CH could be as high as 1%. The sagittal micro oscillating saw is the safest reported to date. Presence of a conduit increases the risk by 2.5 fold.

Adolescent↗