Monitoring cytokine production in peripheral blood during acute graft-versus-host disease following allogeneic bone marrow transplantation.

Plasma concentrations and peripheral blood cells containing cytoplasmic cytokines were monitored during the post-transplant period in 10 patients who had received allogeneic bone marrow transplants (BMT) for the correction of inherited genetic disorders. The presence of CD14-positive cells containing cytoplasmic interleukin-1 alpha and beta in the peripheral blood was indicative of acute graft-versus-host disease (GVHD). Plasma concentrations of IL-1 alpha, IL-1 beta and TNF-alpha were significantly raised in the GVHD group when compared with the uneventful days. There was, however, poor temporal correlation between the plasma concentrations and clinical manifestations of acute GVHD. Cells containing cytoplasmic IL-6 were present in the peripheral blood when patients had clinically suspected and/or microbiologically confirmed infection. The results from this study demonstrate that analysis of peripheral blood cells for cytoplasmic IL-1 alpha and IL-1 beta are better markers of acute GVHD than is monitoring plasma concentrations of these cytokines.

Engraftment rates related to busulphan and cyclophosphamide dosages for displacement bone marrow transplants in fifty children.

The use of busulphan and cyclophosphamide permitted engraftment in 44 of 49 children receiving 'displacement' bone marrow transplants. Three patients who received T-cell-depleted marrow cells from HLA-haploidentical donors failed to engraft and other graft failures were due to inadequate induction dosage. Our standard schedule comprises busulphan 80 mg/m2/day x 4 days (adjusted if necessary to a minimum of 4 mg/kg/day or a maximum of 5 mg/kg/day) followed by cyclophosphamide 2 g/m2/day x 4 days but reduced so as not to exceed 75 mg/kg/day, a maximum dose preferred for patients with full marrows (e.g. those with thalassaemia major). Of 21 recipients of mixed lymphocyte culture (MLC)-negative donor marrow cells with full engraftment at 100 days, there were three late rejections. Of patients transplanted with marrow from MLC-positive donors, one had late rejection after cyclosporin A toxicity had necessitated withdrawal of the drug at day + 146 but six other patients, whose cyclosporin A was stopped routinely 1 year, remain well with full grafts. Ten patients died as a result of graft-versus-host disease. We are therefore exploring new approaches to T-cell depletion and storing autologous marrow for use in the event of graft failure. If necessary, a second transplant with busulphan and cyclophosphamide is best performed at 3 months after full recovery of the host. We conclude that elective transplants can be performed successfully in children with normal immune function without the need for irradiation.

Busulphan and cyclophosphamide cause little early toxicity during displacement bone marrow transplantation in fifty children.

Fifty children were induced with busulphan and cyclophosphamide before bone marrow transplantation. Our standard dose of cyclophosphamide was 2 g/m2 daily for 4 days, but this dosage was reduced if necessary so as not to exceed 75 mg/kg/day. A basal pulse rate that increased by more than 20 beats/min or a reduction in ECG voltage were indications for stopping cyclophosphamide. As a consequence, the fourth dose of cyclophosphamide was omitted for four children. One child died of cardiac arrest related to cyclophosphamide. We used busulphan at a dosage of 4 mg/kg/day for 4 days; neither 'busulphan lung' nor veno-occlusive disease occurred in any patient. The use of busulphan and cyclophosphamide did not guarantee freedom from interstitial pneumonitis, but this seemed to be related rather to the nature of prior treatment and the cytomegalovirus antibody status of the patient. Thus, we have developed a safe chemotherapy schedule for transplantation that avoids the need for radiotherapy and can, if necessary, be repeated after a 3-month interval.

Bone marrow transplantation for thalassaemia: experience of two British centres.

Bone marrow transplantation (BMT) was carried out on 38 patients with thalassaemia major over a period of 9 years; 30 were Asian. In all cases, the donor was an HLA-identical relative. The mean age at transplant was 6.4 years (range 0.5-20 years). Conditioning was busulphan and cyclophosphamide (CY). Cyclosporin (CsA) (n = 30), CsA + methotrexate (n = 6) or CsA + T cell depletion (n = 2) were used for prophylaxis against graft-versus-host disease (GVHD). Thirty-four patients successfully engrafted. Two patients required a second transplant and two achieved mixed chimerism, eventually rejecting their grafts. Nine patients (23.6) developed acute GVHD grade III-IV. Eleven patients (28.9) developed chronic GVHD. There were 11 deaths, 7 within the first 100 days post-BMT. Twenty-seven patients are alive from 156 to 3213 days post-BMT. The actuarial survival at 9 years post-BMT was 70%. The mortality is higher than in previously reported series; possible reasons for this are discussed.

Bone marrow transplantation for Glanzmann's thrombasthenia.

Allogeneic matched bone marrow transplantation (BMT) was performed in a patient with type I Glanzmann's thrombasthenia, a rare, inherited bleeding disorder caused by a deficiency in the platelet membrane glycoprotein IIb-IIIa complex. The patient was a 2-year-old girl with a history of frequent hospitalisation. She was successfully transplanted with BM from her HLA-identical sibling. Engraftment was monitored by analysis of the platelet GPIIb-IIIa complex and by RFLP analysis using a minisatellite probe. Complete engraftment was seen at day +25. The patient has been clinically stable for 19 months. It is proposed that BMT is a suitable treatment for this condition where a matched, related donor is available and at an early stage, before the development of anti-platelet antibodies as a result of repeated transfusions.

Allogeneic bone marrow transplantation for fucosidosis.

Bone marrow transplantation was performed on an 8-month-old boy who was diagnosed as having fucosidosis following the diagnosis of the disease in his older brother. Although he was asymptomatic and his development was normal, abnomalities were found on an MRI scan prior to transplant. In the absence of a suitable related donor, an unrelated volunteer donor was used. Conditioning for the transplant consisted of busulphan and cyclophosphamide. Graft-versus-host disease prophylaxis consisted of in vitro T cell-depletion of the bone marrow and in vivo administration of cyclosporin. The post-transplant period was complicated by moderately severe graft-versus-host disease. Engraftment was documented by the presence of donor levels of alpha-fucosidase, donor blood group and tissue type (difference in the DQ antigen), and chromosomal polymorphism pattern of donor origin. Eighteen months after transplant, there is evidence of mild neurodevelopmental delay. By contrast, his elder sibling showed far greater developmental delay at the same age. The patient's MRI scan shows improvement. We believe this to be the first case of human fucosidosis treated by bone marrow transplantation.

Encephalitis in a 13-year-old boy following 17D yellow fever vaccine.

We report a case of encephalitis following yellow fever vaccine in a healthy 13 year-old-boy. This is the first reported case in a child older than 3 years of age and the second over the age of 9 months, before which time the vaccine is contraindicated for routine immunisation.

A 3-year oral health dose-response study of sodium monofluorophosphate dentifrices with and without zinc citrate: anti-caries results.

A 3-yr clinical trial has been conducted on 3000 12-yr-old children in Lanarkshire, Scotland, with the aim of investigating the effects on oral health of toothpastes containing both sodium monofluorophosphate and zinc citrate, the former being present at fluoride levels of 1000, 1500, and 2500 ppm F. No significant difference in caries increments was found between the group of children using toothpastes incorporating zinc citrate and their counterparts using zinc-free pastes. However, a significant anti-caries dose-response was demonstrated over the SMFP range used. This dose-response was evident for boys and girls and also for the various types of teeth and tooth surfaces.

Postoperative analgesic requirements in patients exposed to positive intraoperative suggestions.

OBJECTIVE: To establish whether positive suggestions given to a patient under general anaesthesia reduce postoperative pain and analgesic requirements. DESIGN: Prospective double blind randomised study. SETTING: Operating theatre and gynaecology ward of a teaching hospital. PATIENTS: 63 Woman undergoing elective abdominal hysterectomy were randomised to be played either a tape of positive suggestions or a blank tape during the operation through a personal stereo system. INTERVENTIONS: Three women were withdrawn from the study. Anaesthesia was standardised for all of the women. Postoperative analgesia was provided through a patient controlled analgesia system for the first 24 hours. Pain scores were recorded every six hours. MAIN OUTCOME MEASURES: Morphine consumption over the first 24 hours after the operation; pain scores. RESULTS: Mean morphine requirements were 51.0 mg (95% confidence interval 42.1 to 60.0 mg in the women played positive suggestions; and 65.7 mg (55.6 to 75.7 mg) in those played a blank tape. The point estimate (95% confidence interval) for the difference of means was 14.6 mg (22.4%) (1.9 (2.9%) to 27.3 mg (41.6%] (p = 0.028). Pain scores were similar in the two groups. CONCLUSION: Positive intraoperative suggestions seem to have a significant effect in reducing patients' morphine requirements in the early postoperative period.

An Unprecedented (1infinity)

A chain of vertex-linked "bare" nido-Ge(9)(2-) clusters (shown in the picture) is featured by the novel polymeric Zintl anion formed from the binary alloy "KGe(4)", ethylenediamine, and [18]crown-6. The polymerization of nido-Ge(9)(4-) clusters is counterintuitive to known two-electron oxidation behavior of nido clusters and the existence of the isolated closo-Ge(9)(2-) ion. The novel semiconducting cluster "wire" establishes direct structural and mechanistic links between molecular Zintl cluster ions with the extended structures of Zintl phases and elemental nanophase materials.