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J Burroughs

Publications and source records attributed to J Burroughs.

16 recordsLinked to original sources

Progenitor content of autologous grafts: mobilized bone marrow vs mobilized blood.

The progenitor content of autologous peripheral blood progenitor and stem cell collections is a major determinant of prompt hematopoietic recovery following autologous stem cell transplantation. We analyzed unstimulated bone marrow (BM) and peripheral blood (PB) apheresis products in comparison to those collected following G-CSF or GM-CSF stimulation. We quantitated their committed (CFU-GM) and primitive (long-term culture-initiating cells, LTC-IC) progenitors in relation to hematologic recovery in 63 patients undergoing autografting for lymphoid malignancies. G-CSF, but not GM-CSF, substantially enriched the committed progenitor content (2.5-3.6-fold) of both PB and BM grafts. G-CSF also enriched the LTC-IC content of BM and PB compared to control grafts. GM-CSF augmented (11.5-fold) the LTC-IC content of stimulated BM, but not GM-CSF-mobilized PB. Neutrophil recovery was substantially quicker in recipients of BM or PB mobilized with G-CSF or GM-CSF. In contrast, red cell and platelet recovery was accelerated in recipients of GM-CSF-stimulated BM (but not PB) and G-CSF-stimulated PB (but not BM). No direct correlation between progenitor dose and hematopoietic recovery for neutrophils, platelets or red cells was observed. Cytokine stimulation can augment the committed and more primitive multilineage progenitor content of BM and PB grafts, to a differing extent. The uncertain relationship with multilineage myeloid recovery emphasizes the limitations in using clonogenic progenitor analyses to assess the adequacy of an autologous graft prior to transplantation.

Adolescent↗

Hematopoietic growth factors for graft failure after bone marrow transplantation: a randomized trial of granulocyte-macrophage colony-stimulating factor (GM-CSF) versus sequential GM-CSF plus granulocyte-CSF.

Delay in hematologic recovery after bone marrow transplantation (BMT) can extend and amplify the risks of infection and hemorrhage, compromise patients' survival, and increase the duration and cost of hospitalization. Because current studies suggest that granulocyte-macrophage (GM) colony-stimulating factor (CSF) may potentiate the sensitivity of hematopoietic progenitor cells to G-CSF, we performed a prospective, randomized trial comparing GM-CSF (250 micrograms/m2/d x 14 days) versus sequential GM-CSF x 7 days followed by G-CSF (5 micrograms/kg/d x 7 days) as treatment for primary or secondary graft failure after BMT. Eligibility criteria included failure to achieve a white blood cell (WBC) count > or = 100/microL by day +21 or > or = 300/microL by day +28, no absolute neutrophil count (ANC) > or = 200/microL by day +28, or secondary sustained neutropenia after initial engraftment. Forty-seven patients were enrolled: 23 received GM-CSF (10 unrelated, 8 related allogeneic, and 5 autologous), and 24 received GM-CSF followed by G-CSF (12 unrelated, 7 related allogeneic, and 5 autologous). For patients receiving GM-CSF alone, neutrophil recovery (ANC > or = 500/microL) occurred between 2 and 61 days (median, 8 days) after therapy, while those receiving GM-CSF+G-CSF recovered at a similar rate of 1 to 36 days (median, 6 days; P = .39). Recovery to red blood cell (RBC) transfusion independence was slow, occurring 6 to 250 days (median, 35 days) after enrollment with no significant difference between the two treatment groups (GM-CSF: median, 30 days; GM-CSF+G-CSF; median, 42 days; P = .24). Similarly, platelet transfusion independence was delayed until 4 to 249 days (median, 32 days) after enrollment, with no difference between the two treatment groups (GM-CSF: median, 28 days; GM-CSF+G-CSF: median, 42 days; P = .38). Recovery times were not different between patients with unrelated donors and those with related donors or autologous transplant recipients. Survival at 100 days after enrollment was superior after treatment with GM-CSF alone. Only 1 of 23 patients treated with GM-CSF died versus 7 of 24 treated with GM-CSF+G-CSF who died 16 to 84 days (median, 38 days) after enrollment, yielding Kaplan-Meier 100-day survival estimates of 96% +/- 8% for GM-CSF versus 71% +/- 18% for GM-CSF+G-CSF (P = .026). These data suggest that sequential growth factor therapy with GM-CSF followed by G-CSF offers no advantage over GM-CSF alone in accelerating trilineage hematopoiesis or preventing lethal complications in patients with poor graft function after BMT.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗

Diffusible factors from the murine cell line M2-10B4 support human in vitro hematopoiesis.

Significantly more primitive human hematopoietic progenitors are maintained and differentiate when cultured separately from the stroma by a microporous membrane ("stroma-noncontact" cultures) than when cultured in direct contact with stromal layers ("stroma-contact" cultures). This suggests that diffusible stroma-derived factors may be sufficient for the in vitro induction of progenitor proliferation and differentiation. To further characterize stroma-derived factors that maintain long-term bone marrow culture initiating cells (LTBMC-IC), we compared the hematopoietic supportive capacity of human marrow stroma with that of the murine marrow stroma-derived fibroblast cell line M2-10B4 as well as two embryonic fibroblast cell lines, the human FHS-173-WE and the murine NIH-3T3 cell lines. We demonstrate that LTBMC-IC, present in human CD34+/HLA-DR- (DR- cells), are maintained equally well and give rise to similar numbers of committed progenitors, that is--colony-forming cells (CFC)--when cultured in contact with human marrow stroma or any cell line feeder (stroma-contact cultures). LTBMC-IC, cultured in marrow stroma or M2-10B4 stroma-noncontact cultures, were maintained significantly better and gave rise to significantly more CFC than when cultured in human marrow stroma or M2-10B4 contact cultures. However, LTBMC-IC maintenance and differentiation in FHS-173-WE or NIH-3T3 noncontact cultures was significantly less than in human marrow stroma or M2-10B4 noncontact cultures. These studies indicate that systematic comparison of diffusible growth stimulatory factors in conditioned media from M2-10B4 cells and FHS-173-WE may lead to the characterization of growth regulatory factors required for in vitro maintenance and differentiation of human primitive LTBMC-IC. Since diffusible factors from the M2-10B4 cell line can support human hematopoiesis, our observations may also have important implications for in vitro stem cell expansion protocols.

Animals↗

Overview of Taxol safety.

The safety profile of Taxol administered intravenously as a single agent has been established based on the experience of 655 patients. Of these patients, 253 were treated in nine phase I studies, and 402 were treated in eight disease-oriented phase II studies. Myelosuppression, specifically neutropenia, was the dose-limiting toxicity in all studies conducted in patients with solid tumors. Neutropenia was schedule dependent and was less severe when Taxol was administered via a 3-hour infusion. Severe hypersensitivity reactions were controlled in the phase II program with a premedication regimen consisting of dexamethasone, an antihistamine, and an H2 blocker. Cardiovascular toxicities were minimal and do not indicate constant electrocardiographic monitoring during Taxol infusions. Peripheral neuropathy was usually mild to moderate and dose related; however, it rarely caused treatment discontinuation. Additional adverse events associated with Taxol include arthralgia/myalgia, mucositis, nausea and vomiting, and alopecia.

Bone Marrow↗

Distinguishing cerebrospinal fluid abnormalities in children with bacterial meningitis and traumatic lumbar puncture.

The characteristics of cerebrospinal fluid (CSF) associated with traumatic lumbar puncture, defined as CSF red blood cell (RBC) count greater than 1000/mm3, were reviewed in 92 previously healthy children greater than 1 month of age; 30 had bacterial meningitis and 62 had negative CSF cultures. The purpose was to distinguish CSF profiles of the two groups despite contamination with peripheral blood elements. In each case, white blood cell (WBC) counts were observed (O) and compared with those predicted (P), calculated as P = CSF RBC X (blood WBC/blood RBC). Comparison of O:P ratios revealed that all 30 patients with bacterial meningitis had ratios greater than or equal to 1, 28 (93%) had ratios greater than 10, and 24 (80%) had ratios greater than 100; by contrast, only 2 patients (3%) with culture-negative CSF had ratios greater than 10, 21 (34%) had ratios of 1-10, and 39 (63%) had ratios less than 1. Significant differences were observed in the rate of O:P ratio greater than or equal to 1 (100% vs. 32%), CSF differential cell count predominance of polymorphonuclear leukocytes (97% vs. 11%), hypoglycorrhachia (73% vs. 3%), and positive Gram's-stained smear for pathologic organisms (80% vs. 0) in those with and without bacterial meningitis, respectively (P less than .0001). Thus, in children greater than 1 month of age, CSF abnormalities associated with bacterial meningitis are rarely obscured by blood contamination from traumatic lumbar puncture.

Cerebrospinal Fluid↗

A critical look at nursing observations.

Our experience has suggested that not only do nurses on hospital wards waste time making too many unnecessary clinical observations, but that it is very difficult to persuade them to modify the pattern of their practice. We therefore conducted a survey by questionnaire among trained nurses in one health district of their everyday ward practice and attitudes to clinical observations. This showed that whilst a majority of nurses questioned believe in the importance of routine observations for patient care, there is a lack of consistency in the criteria and communication procedures used that must seriously limit the value of the information obtained by the individual nurse. We believe that uncritical faith in routine observations is a barrier to rationalizing procedures to optimize efficient use of the professional skills of ward nurses in this regard. There is need for more thought to be given to the problem and in particular it is important that doctors play a more active role in decision making.

Attitude of Health Personnel↗

Relapse following discontinuation of lithium maintenance therapy in adolescents with bipolar I illness: a naturalistic study.

The authors conducted an 18-month naturalistic prospective follow-up study of 37 adolescents whose bipolar I illness had been stabilized with lithium carbonate during inpatient hospitalization. Thirteen of the patients discontinued prophylactic lithium therapy shortly after discharge. The relapse rate of bipolar illness in these 13 patients was nearly three times higher than the rate in patients who continued lithium prophylaxis without interruption. Early relapse among lithium-treated patients was associated with a greater risk of relapsing again. The authors discuss the theoretical and clinical implications of these findings.

Adolescent↗

A controlled family study of anorexia nervosa.

A family study of eating disorders in first and second-degree relatives of anorexia nervosa and nonanorexic psychiatrically ill control probands found increased rates of anorexia-nervosa, bulimia nervosa, and subclinical anorexia nervosa in relatives of anorexic probands. The pattern of familial clustering suggests that these disorders may represent variable expressions of a common underlying psychopathology, although restricter and bulimic subforms of eating disorder may segregate within families. Implications of these findings for understanding factors important to the pathogenesis and subclassification of eating disorders are discussed.

Adolescent↗

Sjögren's syndrome in a young adult.

Sjögren's syndrome is very uncommon in young adults and children. Young patients who have connective tissue disorders should be observed carefully for any signs of this condition. Recurring parotitis, especially in females, should trigger a high index of suspicion that salivary stasis is occurring and that Sjögren's syndrome may be present. Young patients who are diagnosed as having Sjögren's syndrome should be followed very carefully because they are at much greater risk to develop lymphoma.

Adult↗

Anorexia nervosa. An affective disorder?

Follow-up data on 26 patients hospitalized during adolescence for anorexia nervosa are presented. The mean length of follow-up was 4.9 years. There were no mortalities. Only one patient at the time of follow-up was still possibly anorexic. However, a substantial number of the patients did have other eating difficulties. Most striking was the clinical psychopathology present at follow-up, particularly the incidence of affective disorder. A large number of patients manifested depressive symptomatology in both the premorbid and the postmorbid states, as well as at the time of follow-up. A family history of affective disorder was particularly common in the mothers of the anorexic patients. Data from this study are consistent with the hypothesis that there is a strong relationship between anorexia nervosa and affective disorder.

Adolescent↗

A family study of bipolar I disorder in adolescence. Early onset of symptoms linked to increased familial loading and lithium resistance.

Lifetime rates of psychiatric illness were compared in relatives of adolescent probands with bipolar I disorder and in relatives of age-matched schizophrenic controls. Familial aggregation of major affective disorders was observed in bipolar probands, the rate of bipolar I disorder greatly exceeding that reported in relatives of adult bipolar probands. Adolescent probands with childhood onset of psychiatric disturbance were distinguished from probands who had no premorbid childhood psychiatric abnormality in two ways: (1) significantly increased aggregation of bipolar I disorder in first-degree relatives; and (2) poorer antimanic response to lithium carbonate. These data underscore important heterogeneity in adolescent-onset bipolar disorder.

Adolescent↗