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Biomedical subjects

K M Sullivan

Publications and source records attributed to K M Sullivan.

At least 73 records · Page 4Linked to original sources
PubMed1997

Cyclosporine or cyclosporine plus methylprednisolone for prophylaxis of graft-versus-host disease: a prospective, randomized trial.

Patients with a lymphohematopoietic malignancy considered to be at high risk for posttransplant relapse were enrolled in a study to compare the use of cyclosporine (CSP) as a single agent with a combination of methylprednisolone (MP) and CSP for graft-versus-host disease (GVHD) prophylaxis after marrow transplantation from an HLA-identical sibling donor. Sixty patients were randomized to receive CSP only and 62 were randomized to receive CSP plus MP. Daily CSP was started on day -1 (5 mg/kg/d intravenously) and administered at gradually reduced doses until day 180. MP was started on day 7 at 0.5 mg/kg/d, increased to 1.0 mg/kg/d on day 15, started on a taper schedule on day 29, and discontinued on day 72. All 104 evaluable patients (surviving > or =28 days) had sustained engraftment. The incidence rates of grades II-IV acute GVHD were 73% and 60% for patients receiving CSP and CSP plus MP, respectively (P = .01). No difference was seen for grades III-IV GVHD. However, chronic GVHD occurred somewhat more frequently in patients receiving CSP plus MP (44%) than in patients receiving only CSP (21%; P = .02). The incidence of de novo chronic GVHD was marginally higher in patients receiving CSP plus MP (P = .08). No significant differences in the risk of infections were observed. There was a suggestion that the risk of relapse was lower in patients receiving CSP plus MP (P = .10) and, although the overall survival in the two groups was not different (P = .44), there was a slight advantage in favor of CSP plus MP-treated patients for relapse-free survival (P = .07). These results suggest that prophylactic MP, when combined with CSP, has only limited efficacy in acute GVHD prevention and may increase the probability of chronic GVHD.

Adolescent↗
PubMed1997

Marrow transplantation for chronic myeloid leukemia: the influence of plasma busulfan levels on the outcome of transplantation.

The influence of busulfan (BU) plasma concentration on outcome of transplantation from HLA identical family members for the treatment of chronic myelogenous leukemia (CML) was examined in 45 patients transplanted in chronic phase (CP) (n = 39) or accelerated phase (AP) (n = 6). All patients received the same regimen of BU, 16 mg/kg orally and cyclophosphamide (CY), 120 mg/kg intravenously. Plasma concentrations of BU at steady state (C(SS)BU) during the dosing interval were measured for each patient. The mean C(SS)BU was 917 ng/mL (range, 642 to 1,749; median, 917; standard deviation, 213). Of patients with C(SS)BU below the median, seven (five of 18 in CP and two of four in AP) developed persistent cytogenetic relapse and three of these patients died. There were no relapses in patients with C(SS)BU above the median. The difference in the cumulative incidence of relapse between the two groups was statistically significant (P = .0003). C(SS)BU was the only statistically significant determinant of relapse in univariable or multivariable analysis. The 3-year survival estimates were 0.82 and 0.64 for patients with C(SS)BU above and below the median (P = .33). There was no statistically significant association of C(SS)BU with survival or nonrelapse mortality, although the power to detect a difference in survival between 0.82 and 0.64 was only 0.24, similarly C(SS)BU above the median was not associated with an increased risk of severe regimen-related toxicity. We conclude that low BU plasma levels are associated with an increased risk of relapse.

Adult↗
PubMed1997

Infectious morbidity in long-term survivors of allogeneic marrow transplantation is associated with low CD4 T cell counts.

Survivors of allogeneic marrow transplants are immunodeficient for at least 1 year after grafting. Multiple defects of immunity have been found; however, it is not known which defect primarily accounts for the high infectious morbidity of these patients. Twenty-nine allograft recipients who were in complete remission of the original disease were examined for the following parameters of immunity at 1 year after transplant: infection score (gauging the number and severity of infections within the 6 months prior to the annual exam), serum total IgM, IgG, and IgA, anti-Haemophilus influenzae IgG, anti-Streptococcus pneumoniae IgG, skin test reactivity, and the blood counts of B cells, CD4+ T cells, CD8+ T cells, and their subsets. THe only parameter inversely correlated with the infection score was CD4+ T cell count (P = 0.005 in univariable analysis, P = 0.06 in multivariable analysis). We conclude that infectious morbidity of long-term transplant survivors is related to the reconstitution of CD4+ T cells.

Adolescent↗
PubMed1997

Quasielastic light scattering study of the living human lens as a function of age.

PURPOSE: To determine contributions of molecular scattering elements to the increase with age in the light scattered from the human ocular lens in vivo. METHODS: We used quasielastic light scattering to measure autocorrelation functions of the intensity of light scattered in vivo from three locations (anterior, nuclear and posterior) along the optic axis in ocular lenses of 225 subjects, ranging from 17 to 63 years of age. We deduced probability distributions of key parameters (Is, If, Ii, IT), which describe contributions of slowly diffusing (Is), rapidly diffusing (If) and relatively immobile (Ii) scattering elements to the total light intensity (IT) scattered into the collection optics. We deduced characteristic time tau s and tau f that describe the Brownian motion of scattering elements. RESULTS: Probability distributions for each age decile show clearly defined shifts in key parameters with age. IT at the nucleus increases by a factor of three from age 20 to 60 years. This increase is produced principally by an approximate five-fold increase is Is. IT and Is and can be detected with an accuracy of approximately +/- 10%. We estimate threshold values for IT, which mark the boundary beyond which clinical cataract becomes manifest. This boundary represents 6 to 8 times the light scattering efficiency expected from the newborn lens. CONCLUSIONS: This methodology permits a sensitive, quantitative, clinically useful representation of the pre-cataractous molecular changes associated with aging in the living human lens.

Adolescent↗
PubMed1997

Validation of a simple, manual urinary iodine method for estimating the prevalence of iodine-deficiency disorders, and interlaboratory comparison with other methods.

The measurement of urinary iodine in population-based surveys provides a biological indicator of the severity of iodine-deficiency disorders. We describe the steps performed to validate a simple, inexpensive, manual urinary iodine acid digestion method, and compare the results using this method with those of other urinary iodine methods. Initially, basic performance characteristics were evaluated: the average recovery of added iodine was 100.4 +/- 8.7% (mean +/- SD), within-assay precision (CV) over the assay range 0-0.95 mumol/L (0-12 micrograms/dL) was < 6%, between-assay precision over the same range was < 12%, and assay sensitivity was 0.05 mumol/L (0.6 microgram/dL). There were no apparent effects on the method by thiocyanate, a known interfering substance. In a comparison with five other methods performed in four different laboratories, samples were collected to test the method performance over a wide range of urinary iodine values (0.04-3.7 mumol/L, or 0.5-47 micrograms/dL). There was a high correlation between all methods and the interpretation of the results was consistent. We conclude that the simple, manual acid digestion method is suitable for urinary iodine analysis.

Arsenic↗
PubMed1997

Use of thyroid stimulating hormone testing in newborns to identify iodine deficiency.

Iodine deficiency has traditionally been associated with goiter and cretinism. More recently, iodine deficiency has been recognized as the leading worldwide cause of preventable intellectual impairment. Intellectual and neurologic deficits occur because of a lack of thyroid hormone during critical phases of brain development. More sensitive biologic tests may be useful in determining the true extent of iodine deficiency in populations. Thyroid stimulating hormone (TSH) levels among urban newborns from countries with known iodine deficiency problems were determined using a sensitive whole-blood spot assay. Results found prevalences of high TSH (> 5 mU/L whole blood units using a sensitive monoclonal assay) ranging from 32-80% compared with a prevalence of 3% usually found in iodine-replete areas. These findings suggest that developing brains of newborns are at risk from the detrimental effects of iodine deficiency in these urban areas. The results presented suggest the need for effective intervention programs in urban areas as well.

Developing Countries↗
PubMed1997

Factors associated with anemia in refugee children.

A nutrition survey was performed in 1990 among children 6 through 35 mo of age living in Palestinian refugee camps in Syria, Jordan, the West Bank, Gaza Strip and Lebanon. Overall, 67% [95% confidence interval (CI): 66, 68] were anemic (hemoglobin <110 g/L), ranging from 54% in the West Bank to 75% in Syria. The following factors were significantly associated with anemia in one or more of three age groups (6-11.9, 12-23.9 and 24-35.9 mo) by logistic regression: living in Syria, Lebanon, or Gaza [with prevalence odds ratios (POR) in the range of 1.4-2.6 depending on the age group and area, relative to children living in Jordan]; never having been breast-fed (POR = 1.7); male sex (POR = 1.2); maternal illiteracy (POR = 1.4 relative to those with >/=6 y of education); having a recent (within 2 wk) or current episode of fever or diarrhea; and stunting. Recent or current illness and stunting interacted in two age groups with the general trend of stunted children with recent or current illness having high POR. Early childhood anemia is associated with factors reflecting poor socioeconomic status and recent diarrheal and febrile illnesses in Palestinian refugee camps.

Aging↗
PubMed1997

Long-term appearance of lacerations repaired using a tissue adhesive.

BACKGROUND: Histoacryl Blue (HAB), a tissue adhesive, has been shown to decrease laceration repair time, cause less pain to the child, eliminate the need for suture removal, and result in a similar short-term cosmetic outcome compared with conventional suturing. Reports suggest that poor correlation can exist between the short-term and long-term cosmetic outcomes for lacerations repaired by conventional suturing. Therefore, this study compares the long-term cosmetic outcome of HAB to conventional suturing for laceration repair in children. DESIGN: Prospective, randomized clinical trial. PARTICIPANTS: Children presenting an urban pediatric emergency department for laceration repair between October 1994 and February 1995 were eligible. Patients less than 1 or more than 18 years old, those with lacerations more than 5 cm in length, or in areas of high tension or mobility were excluded. INTERVENTIONS: After routine wound management, including subcutaneous closure when deemed necessary, patients were randomized to receive skin sutures or HAB for cutaneous closure. Photographs taken at the 2-month and 1-year follow-up visits were evaluated for cosmetic appearance by two plastic surgeons blinded to the method of repair. RESULTS: Sixty-one children were enrolled: HAB (N = 30), suture (N = 31). Thirty HAB and 25 sutured patients were assessed at 2 months, while 17 HAB and 15 sutured patients were reevaluated at 1 year. Patients that followed-up at 2 months and 1 year were comparable to those with no follow-up in: treatment group (HAB vs suture), demographics, wound characteristics, and initial parental satisfaction. The two plastic surgeons graded the cosmetic appearance of the wounds repaired by HAB to be comparable to those repaired by conventional suturing at both the 2-month and 1-year follow-up. CONCLUSIONS: The use of HAB is an ideal alternative to conventional suturing for the cutaneous closure of low tension lacerations in children with a long-term cosmetic outcome comparable to conventional suturing.

Adolescent↗
PubMed1997

The evolving role of blood and marrow transplantation for the treatment of autoimmune diseases.

With over 4 decades of seminal contributions to the development and application of BMT, Dr. Thomas stresses the importance of collaboration between rheumatologists and transplant clinicians in developing this evolving area of treatment. While the debate concerning the value of TBI in the conditioning regimen and the use of autologous or allogeneic stem cells will continue, he states there is simply no other way to answer these questions than to begin well designed clinical studies. As pointed out by Dr. Hahn, unexpected post-transplant complications may arise in patients with SSc and SLE and possibly require modifications to the transplant procedure similar to the experience in patients with other specific diseases. Other difficulties may be encountered, including restricted funding of the transplant procedure by insurance carriers. The emergence of managed care contracts and payer limitations in the United States described by Dr. Appelbaum could hinder the development of innovative, curative therapies. As initial clinical data are being collected, it is vital to actively support patient referral and participation in clinical studies that will ultimately establish the indications, risks, costs, and benefits of hematopoietic stem cell transplantation for autoimmune disease.

Autoimmune Diseases↗
PubMed1997

Pre-existing autoimmune disease in patients with long-term survival after allogeneic bone marrow transplantation.

We reviewed the experience with allogeneic bone marrow transplantation (BMT) at Fred Hutchinson Cancer Research Center and affiliated Seattle hospitals for patients with preexisting autoimmune diseases. The review was limited to patients who received transplants between 1969 and 1989 from a related donor and who had at least 3 years of relapse-free survival. Of 901 evaluable patients, 11 were identified with a preexisting autoimmune disease and 2 with diseases that were possibly autoimmune in nature. Pretransplant diseases identified in this review included rheumatoid arthritis (n = 1), discoid or systemic lupus (n = 2), insulin dependent Type 1 diabetes (n = 3), hyperthyroidism (n = 4), dermatitis herpetiformis (n = 1), vasculitis (n = 1), and Crohn's disease (n = 1). All 13 patients survive with a median followup of 14 (range, 7-20) years after transplantation from an HLA identical sibling (n = 10), parent (n = 1) or identical twin (n = 2). Pre and post-transplant histories are presented. Variables to be considered in the assessment of any beneficial effect of BMT are discussed, including consideration of different patterns of activity that describe the natural history of various autoimmune diseases. Although autoimmune disease did not recur after allogeneic BMT in these 13 patients, disease and post-transplant variables may confound the interpretation of results from retrospective analysis.

Adolescent↗
PubMed1997

Longterm followup and quality of life after hematopoietic stem cell transplantation.

The success of marrow or blood stem cell transplantation may depend upon events arising months to years later. Transplant regimen related toxicity may include cataract formation due to corticosteroids or total body irradiation (TBI) and endocrine or gonadal dysfunction requiring hormonal replacement. By 15 to 20 years post-transplant, the cumulative incidence of secondary malignancies (including skin cancers) ranges from 4% (no TBI) to 14% (prior irradiation) in patients with previous aplastic anemia. Chronic graft versus-host-disease (GVHD) develops in 33% of HLA-identical sibling transplants and requires 1 to 2 years of immunosuppressive therapy. In allograft recipients free of GVHD, there are very few late infections or complications. These findings are confirmed by multidimensional studies of the quality of life of adult patients surviving 6 to 18 years after marrow transplantation and demonstrate that 80% of patients rate their quality of life as good to excellent and 5%, as poor. Considerations of late effects of transplant and maintenance of quality of life are key considerations when weighing the risks and benefits of stem cell grafts for the treatment of severe autoimmune diseases. Careful followup and reporting of these initial patient cohorts will be vital in determining the longterm success of stem cell transplantation.

Adult↗
PubMed1997

Development of a protocol for allogeneic marrow transplantation for severe systemic sclerosis: paradigm for autoimmune disease.

Some types of severe autoimmune disease are associated with significant morbidity and a high mortality rate. Many of these cases occur in young adults who, even if they survive, become severely debilitated. Systemic sclerosis (SSc) is a paradigm for other severe autoimmune diseases in which patients with poor prognostic features can be identified early in the course of the disease. Allogeneic marrow transplantation may be effective for the control of autoimmune diseases like SSc because the preparative regimen will significantly suppress the host immune system and the antihost effects of the donor immune system in the engrafted marrow will help maintain the suppression of the host immune system. Considering the morbidity and poor prognosis associated with severe SSc and the favorable outcome now associated with allogeneic marrow transplantation from HLA identical siblings for other nonmalignant diseases, Phase I and II studies are warranted. These will evaluate the safety of allogeneic marrow transplantation and explore its role in the management and control of a severe autoimmune disease. We review issues important in the development of an allogeneic marrow transplant protocol for severe SSc, including patient selection, plan of treatment, prevention of graft versus host disease, supportive care, and evaluation after transplant.

Adolescent↗
PubMed1997

Autologous stem cell transplantation for autoimmune diseases: issues in protocol development.

For patients with autoimmune disease resistant to conventional therapy, aggressive strategies employing high dose chemoradiotherapy and autologous stem cell transplant appear to be warranted. Support for this approach comes from animal studies employing marrow transplantation, which have shown promising results. Likewise, longterm control of autoimmune disease has been demonstrated in some survivors of allogeneic transplants for malignancy who incidentally had preexisting autoimmune disease. Initial strategies for autografting will use intensive transplant regimens incorporating cyclophosphamide with or without total body irradiation. Peripheral blood stem cell grafts purified by CD34 selection will be depleted of lymphocytes, and lead to rapid hematologic reconstitution after treatment. Close monitoring for disease responses, adverse effects of intensive immunosuppression, and longterm sequelae of high dose therapies will be required. Initial studies are best performed as close collaborations between rheumatologists and transplant specialists in appropriate research centers.

Animals↗
PubMed1997

Methotrexate and cyclosporine for graft-vs.-host disease prevention: what length of therapy with cyclosporine?

One hundred three patients with leukemia, aplastic anemia, or myelodysplastic syndrome were treated by marrow transplantation from genotypically HLA-identical siblings (n = 92) or HLA haploidentical family members differing for one HLA antigen on the nonshared haplotype (n = 11). To prevent graft-vs.-host disease (GVHD), they were administered postgrafting immunosuppression with a short course of intermittent methotrexate with daily cyclosporine for no more than 11 days. Customarily, we have given cyclosporine for 180 days after transplant. In the current study, we asked whether cyclosporine could be stopped earlier without affecting the risk of chronic GVHD. By day 60, patients who never had acute GVHD, or whose acute GVHD had resolved, were randomized to have cyclosporine stopped (n = 52) or continued for the usual 180 days (n = 51). Results were analyzed with a median follow-up of 9.3 years after transplant, and showed that patients in whom cyclosporine was discontinued on day 60 had a significantly more rapid onset (p = 0.001), but not a significantly higher overall incidence of chronic GVHD than those in whom the drug was stopped on day 180 (43 vs. 54%; p = 0.26). Transplant-related mortality was comparable among patients without preceding acute GVHD, regardless of when cyclosporine was discontinued (11% for both study arms). However, transplant-related mortality appeared to increase among patients with preceding acute GVHD in whom cyclosporine was stopped by day 60 (38 vs. 17%). Results suggest that cyclosporine can safely be discontinued early in patients who never had evidence of acute GVHD, while those with preceding acute GVHD would benefit from a longer course of the drug. Because of the relatively small sample sizes, these results would best be treated as promising preliminary findings that should be confirmed in larger randomized studies.

Adult↗
PubMed1997

Medium-term results of pediatric patients undergoing orthotopic heart transplantation.

To establish the medium-term results of our transplant population, we retrospectively reviewed the charts of 51 consecutive patients who underwent orthotopic heart transplantation between July 1988 and April 1995. These patients comprised two groups: group A consists of 26 patients (age 6 days to 16.4 years, median 1.4 years) with no previous heart surgery, and group B consists of 25 patients (ages 0.1 to 14.3 years, median 8.3 years), all of whom had heart surgery before undergoing transplantation. There was no difference between these groups in early or late survival rates, and neither age at transplantation nor sex was an indicator of survival. There have been 14 deaths, six early (before hospital discharge) and eight late. Early deaths have predominantly been attributed to long-term ventilation and hemodynamic instability before transplantation, and late deaths to graft coronary artery disease (n = 4), acute coronary vasculitis (n = 3), and acute cellular rejection (n = 1). Although infection has resulted in significant morbidity (57 hospital admissions), there have been no late deaths resulting from infection. Sepsis accounts for four early deaths in chronically ill patients. Orthotopic heart transplantation in the pediatric patient with and without previous heart surgery is a viable option for those with end-stage heart disease and those in whom other surgical options carry a prohibitively high mortality rate.

Actuarial Analysis↗
PubMed1997

Collaborative multicenter investigation of marrow transplantation for sickle cell disease: current results and future directions.

We present updated results of a multicenter collaborative investigation of bone marrow transplantation for sickle cell disease. Between September 1991 and April 1997, thirty-four children less than 16 years of age with severe sickle cell disease received marrow allografts from HLA-identical siblings. Indications for transplantation included a history of stroke (n = 17), recurrent acute chest syndrome or sickle pulmonary disease (n = 10), and recurrent vaso-occlusive crises (n = 7). Twenty-one patients received regular red blood cell (RBC) transfusions to prevent complications of sickle cell disease. Patients were prepared for transplantation with busulfan, cyclophosphamide, and antithymocyte globulin or CAMPATH (Cambridge Pathology) antibody. Thirty-two of the 34 patients survived, with a median follow-up of 26.5 months (range, 0.2-66.9 months); and 28 patients demonstrated stable engraftment of donor hematopoietic cells. Graft rejection or recurrence of sickle cell disease occurred in four patients, and two patients died of intracranial hemorrhage or graft-vs.-host disease. In the group of 34 children with symptoms of advanced sickle cell disease, current Kaplan-Meier estimates of survival and event-free survival are 93% and 79%, respectively.

Adolescent↗
PubMed1997

Safeguarding the administration of high-dose chemotherapy: a national practice survey by the American Society for Blood and Marrow Transplantation.

Overdoses of high-dose chemotherapy before hematopoietic cell transplantation are serious adverse events, but their frequency and etiology are unknown. The American Society for Blood and Marrow Transplantation (ASBMT) conducted an anonymous national survey to identify errors in safety practices during the administration of high-dose chemotherapy. The questionnaire was returned from 115 (68%) of 170 hematopoietic transplant centers in the United States. Ninety-four of the programs were university or affiliated centers, 19 were community hospitals, and 41 were founded since 1990. A total of 7650 transplants were reported for 1994: 22% of the programs performed 1-20 transplants, 60% performed 21-100 transplants, and 18% performed more than 100 transplants. Fifteen of the 115 responding centers reported a total of 18 patients inadvertently given overdoses of cisplatin (n=3), carboplatin (n=2), busulfan (n=2), cytosine arabinoside (n=2), cyclophosphamide (n=2), interleukin-2 (n=2), or other agents (n=5) between 1989 and 1994. Cumulative drug doses given as a daily dose (six cases) and nursing infusion errors (six cases) were the most common errors. The estimated chemotherapy overdose error rate was 0.06%, or 6 cases/10,000 transplants, with 95% confidence limits of 0.03-0.11%. The overdose rate among more experienced centers in operation before 1990 was lower than that among newer centers (p < 0.01). Large centers (> 100 transplants performed in 1994) experienced errors at rates lower than those in medium-sized centers (21-100 transplants, p = 0.03). Although the number of events was small in this self-reporting survey, overdoses were noted in 13% of the responding centers, especially among more recently established units. Safety practices need to emphasize multidisciplinary checkpoints at the physician, pharmacist, nursing, and institutional levels. Based on these survey results, ASBMT recommendations for further safeguards for high-dose chemotherapy administration are proposed.

Adult↗