Neonatal transport: time to change?
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Humans↗
Biomedical subjects
D Milligan
Publications and source records attributed to D Milligan.
Engraftment and molecular monitoring of CD34+ peripheral-blood stem-cell transplants for follicular lymphoma: a pilot study.
PURPOSE: A pilot study to validate the use of CD34+ selection (Ceprate SC) of blood stem-cell collection in patients with advanced follicular lymphoma receiving myeloablative chemoradiotherapy. PATIENTS AND METHODS: Seventeen patients were entered onto the protocol. Thirteen of 17 patients have undergone transplantation; the median age is 42.5 years (range, 33 to 51), seven of 13 are stage IVB, two stage IVA, three stage IIIB, and one stage IIB. All except two patients were treated after first or subsequent relapses after receiving cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemotherapy to achieve a good partial (six of 13) or complete (seven of 13) response before stem-cell mobilization with cyclophosphamide 3 g/m2 and filgrastim 300 microg once daily. RESULTS: Eleven of 13 patients had a detectable t(14;18) by nested polymerase chain reaction (PCR). Median CD34+ count before selection was 2.9 x 10(6)/kg (range, 1.17 to 11.3) and after CD34+ selection was 1.54 x 10(6)/kg (range, 0.88 to 7.6) with a median CD34+ yield of 62.4% (range, 17% to 95%) and purity of 60% (range, 39.3% to 73%). Of the 11 patients known to have t(14;18), 10 had PCR-detectable contamination of stem-cell harvests that became PCR negative in six of the 10 after CD34+ selection. Engraftment was rapid with a median day to absolute neutrophil count (ANC) greater than 0.5 x 10(9)/L of 13 days (range, 11 to 21) and platelet count greater than 20 x 10(9)/L of 14 days (range, 10 to 44). With a median follow-up duration of 15 months, three patients have remained persistently PCR-positive, two of whom received PCR-positive stem cells. Two have relapsed. Of the seven patients who received PCR-negative stem cells, five have had no PCR-detectable disease in posttransplant bone marrow samples. CONCLUSION: Longer follow-up duration is required to determine the significance of these findings, but we have confirmed the feasibility of CD34+ selected cells to deplete peripheral-blood stem cells of tumor cells from patients undergoing high-dose therapy for follicular lymphoma.
Adult↗
Crystal structure of an antagonist mutant of human growth hormone, G120R, in complex with its receptor at 2.9 A resolution.
Human growth hormone binds two receptor molecules and thereby induces signal transduction through receptor dimerization. At high concentrations, growth hormone acts as an antagonist because of a large difference in affinities at the respective binding sites. This antagonist action can be enhanced further by reducing binding in the low affinity binding site. A growth hormone antagonist mutant Gly-120 --> Arg, has been crystallized with its receptor as a 1:1 complex and the crystal structure determined at 2.9 A resolution. The 1:1 complex is remarkably similar to the native growth hormone-receptor 1:2 complex. A comparison between the two structures reveals only minimal differences in the conformations of the hormone or its receptor in the two complexes, including the angle between the two immunoglobulin-like domains of the receptor. Further, two symmetry-related 1:1 complexes in the crystal form a 2:2 complex with a large solvent inaccessible area between two receptor molecules. In addition, we present here a native human growth hormone-human growth hormone-binding protein 1:2 complex structure at 2.5 A resolution. One important difference between our structure and the previously published crystal structure at 2.8 A is revealed. Trp-104 in the receptor, a key residue in the hormone-receptor interaction, has an altered conformation in the low affinity site enabling a favorable hydrogen bond to be formed with Asp-116 of the hormone.
Crystallography, X-Ray↗
Dose intensification with autologous bone-marrow transplantation in relapsed and resistant Hodgkin's disease: results of a BNLI randomised trial.
High-dose chemotherapy and radiotherapy with autologous bone-marrow transplantation (ABMT) are increasingly used for the treatment of relapsed and resistant Hodgkin's disease, although there has been no randomised trial of this treatment. The British National Lymphoma Investigation therefore undertook a randomised comparison of high-dose chemotherapy (BEAM = carmustine, etoposide, cytarabine, and melphalan) plus ABMT with the same drugs at lower doses not requiring bone-marrow rescue (mini-BEAM) in patients with active Hodgkin's disease, for whom conventional therapy had failed. 20 patients were assigned treatment with BEAM plus ABMT and 20 mini-BEAM. All have been followed up for at least 12 months (median 34 months). 5 BEAM recipients have died (2 from causes related to ABMT and 3 from disease progression) compared with 9 mini-BEAM recipients (all disease progression). This difference was not significant (p = 0.318). However, both event-free survival and progression-free survival showed significant differences in favour of BEAM plus ABMT (p = 0.025 and p = 0.005, respectively). Recruitment to the trial became increasingly difficult because patients refused randomisation and requested ABMT. It was therefore closed early (40 patients rather than 66 intended). Nevertheless, we found a dose-response effect in these patients with relapsed and resistant Hodgkin's disease. High doses facilitated by ABMT can lead to better disease-free survival.
Adolescent↗
Treatment of aplastic anaemia (AA) with antilymphocyte globulin (ALG) and methylprednisolone (MPred) with or without androgens: a randomized trial from the EBMT SAA working party.
134 patients with acquired aplastic anaemia (AA) were given HALG 15 mg/kg/d for 5 d and methylprednisolone for 1 month, and randomized to receive (n = 69) or not (n = 65) oxymetholone 2 mg/kg/d p.o. daily for 4 months. Early mortality (< 120 d) was comparable in the two arms 12/69 (17%) and 11/65 (17%), and correlated with the severity of the disease (39%, 10% and 6% respectively in patients with neutrophil counts (PMN) < 0.2, 0.2-0.5, > 0.5 x 10(9)/l). The response rate at 120 d was significantly greater in patients receiving androgens (56% v 40%; P = 0.04); it was 68% v 48% (P = 0.02) in patients surviving 120 d, and 78% v 27% (P = 0.03) in females with PMN less than 0.5 x 10(9)/l. In a multivariate Cox analysis on patients with less than 0.5 x 10(9)/l PMN, the probability of responding without androgens was reduced compared to the androgen treatment arm (P = 0.05). Survival was comparable in the two groups (71% v 65%). It was superior (74% v 50%), but not significantly (P = 0.1) in females with PMN < or = 0.5 x 10(9)/l receiving androgens. Side-effects, including biochemical abnormalities and virilization, could be controlled and were reversible. In conclusion, the addition of androgens to HALG and methylprednisolone as first line treatment of aplastic anaemia significantly improves the response rate at 4 months, particularly in females with low neutrophil counts, although there is no significant effect on short-term survival. The reversible side-effects warrant the use of androgens as an adjunct to the first course of ALG in females with severe AA.
Adolescent↗
The effect of altitude on umbilical cord blood gases.
OBJECTIVE: Analysis of umbilical cord blood acid-base status has proven useful in the immediate care and resuscitation of the newborn and provides an objective measure of the intrapartum fetal environment. Our study was designed to determine whether there are any significant differences in the acid-base status of neonates delivered at a relatively high altitude of 6000 ft compared with sea-level controls. METHODS: Our study population consisted of 300 women who had undergone spontaneous vaginal delivery after uncomplicated labor; 150 delivered at an institution located at an elevation of 5900 ft and the remainder at an elevation of 87 ft. Exclusion criteria were hypertensive disease, diabetes, suspected fetal growth retardation, fetal distress, meconium-stained amniotic fluid, and chorioamnionitis. All patients received continuous electronic fetal monitoring, and tracings were reviewed by a physician blinded to the umbilical acid-base results. Umbilical cord arterial and venous samples were collected and analyzed within 30 minutes of delivery. RESULTS: Compared with sea-level controls, neonates delivered at high altitude had a significantly higher mean pH with lower mean carbon dioxide pressure values in both arterial and venous specimens (P less than .05). The difference between the mean arterial pH values was 0.026 (P less than .05, 95% confidence interval [CI] 0.015-0.037) and mean venous values was 0.037 (P less than .05, 95% CI 0.027-0.047). There were no significant differences in the arterial or venous oxygen pressure or oxygen saturation values between the study and control groups. There was a significant decrease in the mean birth weight of 320 g (P less than .05, 95% CI 199.5-441.3) and higher pre-delivery hematocrit values (2.4%; P less than .05, 95% CI 1.6-3.2) in the high-altitude population compared with the sea-level group. CONCLUSIONS: Neonates delivered at high altitude have significant alterations in umbilical blood acid-base measurements compared with neonates at sea level. Other significant differences include a lower infant birth weight and a higher maternal hematocrit relative to pregnant women at sea level.
Acid-Base Equilibrium↗
Transmission of Proteus syndrome from father to son?
We present a male infant with cranial hemi-hypertrophy, a lymphangioma, a lipoma, and epidermal naevi. A diagnosis of Proteus syndrome was made. His father had had a large lymphangioma resected from the right side of the face as a child. We propose that Proteus syndrome has been transmitted from father to son.
Adult↗
Successful treatment of acute myeloid leukemia beyond first remission with autologous bone marrow transplantation using busulfan/cyclophosphamide and unpurged marrow: the British autograft group experience.
The results in 34 adult patients with acute myeloid leukemia (AML) who have undergone autologous bone marrow transplantation (ABMT) using busulfan and cyclophosphamide (Bu/Cy) in 12 United Kingdom (UK) centers have been analyzed. There were 19 females and 15 males; median age was 40 years (range, 21 to 62 years). Nine patients were in first relapse; 25 were in second remission. The median time of first remission for the whole group was 11.5 months (range, 1 to 56 months). All the patients in first relapse and six patients in second remission received first remission marrow. The leukemia-free survival (LFS) for the patients in first relapse was 33%, with a median follow-up of 20 months. The LFS for the patients in second remission was 48% with a median follow-up of 26 months. The length of second remission exceeds the length of first remission in 14 patients. Considerable toxicity with hemorrhagic cystitis (four patients; none fatal), venoocclusive disease (four patients; one fatal), pneumonitis (four patients; one fatal), intracranial hemorrhage (two patients; two fatal) has occurred. There have been four procedure-related deaths (12%). Hematologic recovery was satisfactory for neutrophils (median time to 0.5 x 10(9)/L, 22 days [range, 11 to 101 days]), but very slow for platelets (median time to 50 x 10(9)/L, 62 days [range, 15 to 1,080 days]). This study suggests that the use of Bu/Cy with ABMT for patients beyond first remission in AML compares favorably with chemotherapy, and although the procedure-related mortality is acceptable, it is associated with protracted platelet recovery.
Acute Disease↗
Changes in breast volume during normal menstrual cycle and after oral contraceptives.
The volume of the left and right breasts was measured daily in four nulliparous women during normal menstrual cycles and after the use of oral contraceptives. Breast volume increased significantly in the second half of both normal and contraceptive-controlled cycles. The mean total change in volume throughout the cycle was 100 ml under natural conditions and 66 ml on oral contraceptives.
Adult↗
Update of guidelines for the prevention and treatment of infection in patients with an absent or dysfunctional spleen.
Guidelines for the prevention and treatment of infection in patients with an absent or dysfunctional spleen were first published by the British Committee for Standards in Haematology in 1996. Key aspects of these guidelines related to anti-infective prophylaxis, immunisation schedules and treatment of proven or suspected infection. A recent review of the guidelines was undertaken, with a view to updating the recommendations where necessary The guideline review process did not reveal any major change in patient groups considered at risk. Occupational exposure to certain pathogens may, however, be a new risk factor for some infections. The recommendations for anti-infective prophylaxis remain unchanged. New recommendations for vaccination include the use of meningococcal group C vaccine in previously non-immunised hyposplenic patients and a need to consider the use of seven-valent pneumococcal vaccine. Recommendations for treatment of suspected or proven infection have not been significantly amended, but a local protocol should take into account relevant resistance patterns. There is an identified urgent need for further research into the effectiveness of varying vaccination strategies in the hyposplenic patient, and audit of infective episodes in this patient group should continue long term. Key guidelines are summarised below, together with grades of recommendation.
Antibiotic Prophylaxis↗