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Biomedical subjects

M Briggs

Publications and source records attributed to M Briggs.

At least 19 recordsLinked to original sources

Patients' perceptions of the impact of treatments and products on their experience of leg ulcer pain.

OBJECTIVE: Very little research has explored patients' experience of pain with different cleansing agents and dressings. We therefore undertook a longitudinal study of their impact on leg ulcer pain. METHOD: Patients with leg ulcers referred to community nurses were eligible to participate. They were followed up for six months, completing questionnaires about the impact on pain of each wound treatment used. A treatment episode was defined as the use of a wound cleansing agent, primary dressing and bandages. When one aspect of treatment changed, a new treatment episode began. RESULTS: There were 210 treatment episodes for 96 leg ulcer patients. In 206 episodes cleansing agents were used. Cleansing caused pain in 22% of episodes and relieved pain in 27%. Of the five most commonly used dressing types, low-adherent dressings were the least likely to cause pain. Only 56% of patients were able to tolerate full compression bandaging and pain was the most common reason for non-compliance. CONCLUSION: A substantial proportion of patients felt that leg ulcer treatments caused pain. A greater emphasis on the impact of treatment on pain and healing is warranted both clinically and in research.

Aged↗

A disorder resembling pseudoachondroplasia but without COMP mutation.

Pseudoachondroplasia (PA) is an autosomal dominant skeletal dysplasia characterized by disproportionate short stature, generalized ligamentous laxity, irregular epi-metaphyseal ossification, and vertebral anomalies that regress with age. It usually manifests in the second year of life or later. The clinically and radiographically variable disorder is caused by mutations in the COMP gene. Parental gonadal mosaicism may lead to recurrence of the disorder in children of unaffected parents. Here, we describe sibs with bone changes similar to those seen in very severe PA born to clinically and radiographically unaffected parents. Sequencing of all 19 exons of the COMP gene failed to disclose a mutation. The sibs appear to be affected by a disorder resembling PA but resulting from a defect of an extracellular matrix protein other than COMP. It may be suspected in patients with unusually severe dwarfism, severe epi-metaphyseal abnormalities, and persistent platyspondyly.

Achondroplasia↗

Case selection in macular relocation surgery for age related macular degeneration.

BACKGROUND: To date there has been no randomised controlled trial demonstrating the safety and efficacy of macular relocation surgery (MRS) for age related macular degeneration (AMD). Vision can be improved in some patients and made worse in others despite successful surgery or because of complications. PURPOSE: To determine which patients would benefit from MRS. METHODS: Twenty nine patients with exudative AMD took part in a prospective, non-comparative, interventional study. Macular relocation surgery involved phacoemulsification, vitrectomy, 360 degrees retinotomy, excision of choroidal neovascular membrane, and macular relocation using an infusion of 5-fluorouracil and low molecular weight heparin as adjuvant to prevent proliferative vitreoretinopathy. Patients underwent protocol refraction preoperatively and six-monthly postoperatively by designated optometrists. Preoperative fundus fluorescein angiograms were read by masked observers and the lesions were classified according to a set protocol. The main outcome measures were visual improvement, final vision of better than 20/400, reading speed, critical print size. Logistic and multiple stepwise linear regressions were used to identify independent factors which predicted the main outcomes. RESULTS: Preoperative visual acuity (20/120 or worse) and lesion type (predominantly classic or submacular haemorrhage) were significantly associated with visual improvement (coefficient of regression B = 26.8, p<0.001 and B = 14.9 with p = 0.045 respectively). There were no significant independent factors which predicted a final distance logMAR visual acuity of 1.3 (20/400) or any arbitrary definition of blindness. CONCLUSIONS: The study showed that it was possible to select cases that were more likely to experience an improvement in vision following MRS.

Aged↗

Toxoplasma gondii, Neospora caninum, Sarcocystis neurona, and Sarcocystis canis-like infections in marine mammals.

Toxoplasma gondii, Neospora caninum, Sarcocystis neurona, and S. canis are related protozoans that can cause mortality in many species of domestic and wild animals. Recently, T. gondii and S. neurona were recognized to cause encephalitis in marine mammals. As yet, there is no report of natural exposure of N. caninum in marine mammals. In the present study, antibodies to T. gondii and N. caninum were assayed in sera of several species of marine mammals. For T. gondii, sera were diluted 1:25, 1:50, and 1:500 and assayed in the T. gondii modified agglutination test (MAT). Antibodies (MAT > or =1:25) to T. gondii were found in 89 of 115 (77%) dead, and 18 of 30 (60%) apparently healthy sea otters (Enhydra lutris), 51 of 311 (16%) Pacific harbor seals (Phoca vitulina), 19 of 45 (42%) sea lions (Eumetopias jubatus) [corrected] 5 of 32 (16%) ringed seals (Phoca hispida), 4 of 8 (50%) bearded seals (Erignathus barbatus), 1 of 9 (11.1%) spotted seals (Phoca largha), 138 of 141 (98%) Atlantic bottlenose dolphins (Tursiops truncatus), and 3 of 53 (6%) walruses (Odobenus rosmarus). For N. caninum, sera were diluted 1:40, 1:80, 1:160, and 1:320 and examined with the Neospora agglutination test (NAT) using mouse-derived tachyzoites. NAT antibodies were found in 3 of 53 (6%) walruses, 28 of 145 (19%) sea otters, 11 of 311 (3.5%) harbor seals, 1 of 27 (3.7%) sea lions, 4 of 32 (12.5%) ringed seals, 1 of 8 (12.5%) bearded seals, and 43 of 47 (91%) bottlenose dolphins. To our knowledge, this is the first report of N. caninum antibodies in any marine mammal, and the first report of T. gondii antibodies in walruses and in ringed, bearded, spotted, and ribbon seals. Current information on T. gondii-like and Sarcocystis-like infections in marine mammals is reviewed. New cases of clinical S. canis and T. gondii infections are also reported in sea lions, and T. gondii infection in an Antillean manatee (Trichechus manatus manatus).

Agglutination Tests↗

A pH-sensitive fluor, CypHer 5, used to monitor agonist-induced G protein-coupled receptor internalization in live cells.

G protein-coupled receptors (GPCRs) are the largest family of proteins involved in transmembrane signal transduction and are actively studied because of their suitability as therapeutic small-molecule drug targets. Agonist activation of GPCRs almost invariably results in the receptor being desensitized. One of the key events in receptor desensitization is the sequestration of the receptor from the cell surface into acidic intracellular endosomes. Therefore, a convenient, generic, and noninvasive monitor of this process is desirable. A novel, pH-sensitive, red-excited fluorescent dye, CypHer 5, was synthesized. This dye is non-fluorescent at neutral pH and is fluorescent at acidic pH. Anti-epitope antibodies labeled with this dye were internalized in an agonist concentration- and time-dependent manner, following binding on live cells to a range of GPCRs that had been modified to incorporate the epitope tags in their extracellular N-terminal domain. This resulted in a large signal increase over background. When protonated, the red fluorescence of CypHer 5 provides a generic reagent suitable for monitoring the internalization of GPCRs into acidic vesicles. This approach should be amenable to the study of many other classes of cell surface receptors that also internalize following stimulation.

Animals↗

Stimulation of autologous proliferative and cytotoxic T-cell responses by "leukemic dendritic cells" derived from blast cells in acute myeloid leukemia.

Effective presentation of tumor antigens is fundamental to strategies aimed at enrolling the immune system in eradication of residual disease after conventional treatments. Myeloid malignancies provide a unique opportunity to derive dendritic cells (DCs), functioning antigen-presenting cells, from the malignant cells themselves. These may then co-express leukemic antigens together with appropriate secondary signals and be used to generate a specific, antileukemic immune response. In this study, blasts from 40 patients with acute myeloid leukemia (AML) were cultured with combinations of granulocyte-macrophage colony-stimulating factor, interleukin 4, and tumor necrosis factor alpha, and development to DCs was assessed. After culture, cells from 24 samples exhibited morphological and immunophenotypic features of DCs, including expression of major histocompatibility complex class II, CD1a, CD83, and CD86, and were potent stimulators in an allogeneic mixed lymphocyte reaction (MLR). Stimulation of autologous T-cell responses was assessed by the proliferative response of autologous T cells to the leukemic DCs and by demonstration of the induction of specific, autologous, antileukemic cytotoxicity. Of 17 samples, 11 were effective stimulators in the autologous MLR, and low, but consistent, autologous, antileukemic cytotoxicity was induced in 8 of 11 cases (mean, 27%; range, 17%-37%). This study indicates that cells with enhanced antigen-presenting ability can be generated from AML blasts, that these cells can effectively prime autologous cytotoxic T cells in vitro, and that they may be used as potential vaccines in the immunotherapy of AML.

Acute Disease↗

Comparison of megakaryopoiesis in vitro of paired peripheral blood progenitor cells and bone marrow harvested during remission in patients with acute myeloid leukaemia.

We have studied paired peripheral blood progenitor cells (PBPC) and bone marrow (BM) samples from 12 acute myeloid leukaemia (AML) patients following intensive chemotherapy, and assessed direct granulocyte-macrophage colony-forming units (CFU-GM), erythroid burst-forming units (BFU-E), megakaryocyte CFU (CFU-Mk) numbers and the production of CD61+ (platelet glycoprotein IIIa) cells in suspension culture in response to various haemopoietic growth factor combinations. We found that CFU-GM and BFU-E numbers per 105 mononuclear cells were similar in both AML PBPC and BM harvests; CFU-Mk numbers, however, were significantly higher in PBPC than BM. In addition, the higher total white cell count of the PBPC harvests meant that PBPC have much higher numbers of total progenitors per collection. CD61+ cell numbers in suspension cultures of AML PBPC and BM were lower than those of harvested normal marrow. However, response to pegylated recombinant human megakaryocyte growth and development factor (PEGrHuMGDF) both alone and in combination with other growth factors was qualitatively similar to that of normal BM. As with normal BM, response to PEGrHuMGDF alone did not increase further with addition of granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage CSF (GM-CSF), interleukin 6 (IL-6) or erythropoietin (EPO) in the AML PBPC and BM. Further responses over PEGrHuMGDF alone were seen when added with stem cell factor (SCF) or with a combination of SCF + IL-3 + EPO in both AML PBPC and BM cultures; however, the magnitude of the response was greater in the PBPC cultures. Response to PEGrHuMGDF + IL-3 was seen in the PBPC cultures but not in the AML BM. These data suggest that, in AML patients, there are proportionally more megakaryocyte progenitor cells in the mobilized PBPC than in the BM harvests, which would explain the more rapid platelet recovery following PBPC autografts.

Acute Disease↗

Induction of LPL gene expression by sterols is mediated by a sterol regulatory element and is independent of the presence of multiple E boxes.

Overexpression of the adipocyte differentiation and determination factor-1 (ADD-1) or sterol regulatory element binding protein-1 (SREBP-1) induces the expression of numerous genes involved in lipid metabolism, including lipoprotein lipase (LPL). Therefore, we investigated whether LPL gene expression is controlled by changes in cellular cholesterol concentration and determined the molecular pathways involved. Cholesterol depletion of culture medium resulted in a significant induction of LPL mRNA in the 3T3-L1 preadipocyte cell line, whereas addition of cholesterol reduced LPL mRNA expression to basal levels. Similar to the expression of the endogenous LPL gene, the activity of the human LPL gene promoter was enhanced by cholesterol depletion in transient transfection assays, whereas addition of cholesterol caused a reversal of its induction. The effect of cholesterol depletion upon the human LPL gene promoter was mimicked by cotransfection of expression constructs encoding the nuclear form of SREBP-1a, -1c (also called ADD-1) and SREBP-2. Bioinformatic analysis demonstrated the presence of 3 potential sterol regulatory elements (SRE) and 3 ADD-1 binding sequences (ABS), also known as E-box motifs. Using a combination of in vitro protein-DNA binding assays and transient transfection assays of reporter constructs containing mutations in each individual site, a sequence element, termed LPL-SRE2 (SRE2), was shown to be the principal site conferring sterol responsiveness upon the LPL promoter. These data furthermore underscore the importance of SRE sites relative to E-boxes in the regulation of LPL gene expression by sterols and demonstrate that sterols contribute to the control of triglyceride metabolism via binding of SREBP to the LPL regulatory sequences.

Adipocytes↗

Support for carers of people with Alzheimer's type dementia.

BACKGROUND: Research has highlighted the problems for carers of people with dementia. These include the effective loss of companionship and support of a life partner, social isolation and complex financial, legal and social decision making. The burden of caring is financially, emotionally and physically significant. Studies of the effects of ways of supporting carers and reducing the burden of caring often examine a range of outcomes. Probably because of these characteristics, no formal overview of this area of service provision has been undertaken. Moreover, the term 'intervention' in relation to caregivers of people with Alzheimer's disease is open to wide variations in interpretation at the level of service provision. Interventions range from the application of 'hi-tech' computer technology for socialy isolated carers, to the formation of specialist support groups and respite services. OBJECTIVES: The objective of this review is to provide an assessment of the effectiveness of health and/or social interventions designed to help support the carers of people with Alzheimer's-type dementias. SEARCH STRATEGY: The Cochrane Controlled Trials Register was searched using the terms 'carer*' and 'caregiv*'. See the Cochrane Dementia & Cognitive Impairment group's details for the full search strategy. SELECTION CRITERIA: All randomised trials in which primary carers of people with Alzheimer's disease are allocated to either intervention or non-intervention/control groups and where the intervention was provided by healthcare and/or social services. DATA COLLECTION AND ANALYSIS: Data was extracted by both reviewers and was found to be unsuitable for quantitative synthesis. A qualitative overview is presented and structured according to the comparisons used in the review. Weighted Mean Differences (weighted by sample size) for each outcome and its subcategories are also presented. MAIN RESULTS: The results of the review are inconclusive. No evidence was found for the following comparison interventions: 1) individualised service assessment and planning versus conventional support 2) technology-based carer networking (via computers or telephones) versus conventional support 3) carer-education/training versus conventional support 4) multi-faceted/dimensional strategies (such as specialised carer assessment and training) versus conventional support Whilst the overview suggests little or no evidence that interventions to support caregivers of people with Alzheimer's disease are of quantifiable benefit, the poor quality and small sample sizes of the studies, as well as the diversity of interventions examined and outcomes reported, mean that this conclusion cannot be put forward without the need for caution, particularly as some of the studies put forward qualitative evidence which contradicts this conclusion. REVIEWER'S CONCLUSIONS: With the limited nature of the research evidence in mind, it is not possible to recommend either wholesale investment in caregiver support programmes or withdrawal of the same. With the addition of further studies in future updates of this review, expected in early 1999, this presently inconclusive picture may become clearer. A number of conclusions relating to future areas of research can be put forward with more conviction. Specifically, 1) Future trials need to examine interventions included in the existing knowledge base on Alzheimer's carer-supportive interventions. 2) Outcome measures used should mirror those in similar studies. 3) Outcome measures need to be clinically and 'lay' relevant. 4) Trials need to be of longer duration given the 7-10 years median life expectancy of people with Alzheimer's Disease. 5) Sample sizes need to be increased and calculated properly given the likelihood of a moderate intervention effect (if any). 7) Blinding at the outcome assessment stage needs to be a part of future basic trial designs if bias is to be avoided. 8) If reviews are to have their power increased then quality o

Alzheimer Disease↗

Topical agents or dressings for pain in venous leg ulcers.

BACKGROUND: Venous leg ulcers affect up to 1 per cent of people at some time in their life. These ulcers are often painful and some clinicians choose dressings to reduce the pain both during and between dressing changes. OBJECTIVES: To assess the effectiveness of dressings, local anaesthetics/analgesics for pain relief in venous leg ulceration. SEARCH STRATEGY: Cochrane Wounds Group Register and the Cochrane Collaboration Field in Complementary Medicine were searched. Cochrane Pain Palliative and Supportive Care Group and Cochrane Wounds Group strategy were combined and used. SELECTION CRITERIA: All randomised controlled trials which evaluated local interventions used to relieve venous leg ulcer pain were considered. Pain was defined as either persistent pain or pain at dressing changes or debridement. DATA COLLECTION AND ANALYSIS: Eligibility for inclusion was confirmed by two reviewers who independently assessed the all potential trials. Details of eligible studies were summarised using a data extraction sheet which was checked by the second reviewer. MAIN RESULTS: No trial evaluated interventions for persistent pain. Three trials compared a eutectic mixture of local anaesthetic (EMLA) versus placebo for pain at debridement. All 3 trials reported a significant difference in pain in favour of EMLA, however, one of the trials favoured placebo in terms of number of ulcers healed at the end of the trial and another trial noted an increased incidence of burning and itching with the use of EMLA. REVIEWER'S CONCLUSIONS: EMLA may provide pain relief for venous leg ulcer debridement however, the effect of the product on ulcer healing and the incidence of itching and burning is unclear. Research is required to address questions such as the benefits of leg ulcer debridement and the impact of EMLA on healing and the incidence of burning and itching. There were no trials addressing the treatment of persistent pain and further research is warranted.

Administration, Topical↗

Validation therapy for dementia.

BACKGROUND: Validation therapy is a "therapy for communicating with old-old people who are diagnosed as having Alzheimer's disease and related dementia". The approach was developed by Naomi Feil between 1963 and 1980. She classifies individuals with cognitive impairment as having one of four stages on a continuum of dementia: these stages are Malorientation, Time Confusion, Repetitive Motion and Vegetation. The benefits of Validation therapy for patients are reported by Feil as restoration of self worth, minimisation of the the degree to which patients withdraw from the outside world, promotion of communication and interaction with other people, reduction of stress and anxiety, stimulation of dormant potential, help in resolving unfinished life tasks, facilitation of independent living for as long as possible. These benefits are highly desirable and Validation therapy but there is a need to show them on the basis of substantive research yielding strong evidence across a number of well designed studies. The potential number of people that might benefit from the implementation of Validation therapy is considerable given the increasing incidence of dementia. OBJECTIVES: To evaluate the effectiveness of using validation therapy with people diagnosed as having senile dementia of the Alzheimer's type, other forms of dementia, or cognitive impairment. SEARCH STRATEGY: The Cochrane Controlled Trials Register was searched by the Cochrane Dementia and Cognitive Impairment Group Coordinator and relevant references were forwarded to the primary reviewer. The reviewers carried out independent searches of the following electronic databases - MEDLINE, EMBASE, Eureka, CINAHL, PSYCLIT, RLIN, SIGLE and SOCIOFILE. The following key terms were used in searches; validation-therapy, dementia, cognitive impairmnent, communication, and random*-control*. An author search using Feil and Naomi was also carried out. Personal contact was made with the Validation Institute, Cleveland, Ohio USA and unpublished studies were sought by direct contact with the relevant authors, or institutions. Key individuals who might provide further information regarding validation therapy were contacted. SELECTION CRITERIA: All randomised controlled trials (RCTs) and quasi-randomised controlled trials examining Validation therapy as an intervention for dementia were considered for inclusion in review. The criteria for inclusion/exclusion comprised systematic assessment of the quality of study design and the risk of bias, using a standard data extraction form. Outcome measures of cognitive and/or behavioural change were required. DATA COLLECTION AND ANALYSIS: Data were extracted independently by both reviewers, using a previously tested data extraction form. Authors were contacted for data not provided in the papers. Psychological scales measuring cognitive and behavioural changes were examined. Subcategory analysis was performed due to the diversity of the scales and the inability to combine data across studies. MAIN RESULTS: Only three studies were identifed that potentially met the inclusion criteria and only two small studies were able to be obtained. The Peoples 1982 study was not obtainable through a British Library loan because the cost was prohibitive. Data from 2 studies were entered using MetaView - Robb 1986, Toseland et al 1997, incorporating data on a total of 87 patients (32 in the experimental group, and 55 in the control groups (usual care 34 and social contact 21)). It was not possible to pool the data from the two included studies, and therefore, subcategory analyses were carried out. The analysis of the data failed to reveal statistically significant results although there were trends toward favouring validation therapy for some outcomes. (ABSTRACT TRUNCATED)

Alzheimer Disease↗

Prediction of interindividual variation in drug plasma levels in vivo from individual enzyme kinetic data and physiologically based pharmacokinetic modeling.

A strategy is presented to predict interindividual variation in drug plasma levels in vivo by the use of physiologically based pharmacokinetic modeling and human in vitro metabolic parameters, obtained through the combined use of microsomes containing single cytochrome P450 enzymes and a human liver microsome bank. The strategy, applied to the pharmaceutical compound (N-[2-(7-methoxy-1-naphtyl)-ethyl]acetamide), consists of the following steps: (1) estimation of enzyme kinetic parameters K(m) and V(max) for the key cytochrome P450 enzymes using microsomes containing individual P450 enzymes; (2) scaling-up of the V(max) values for each individual cytochrome P450 involved using the ratio between marker substrate activities obtained from the same microsomes containing single P450 enzymes and a human liver microsome bank; (3) incorporation into a physiologically based pharmacokinetic model. For validation, predicted blood plasma levels and pharmacokinetic parameters were compared to those found in human volunteers: both the absolute plasma levels as well as the range in plasma levels were well predicted. Therefore, the presented strategy appears to be promising with respect to the integration of interindividual differences in metabolism and prediction of the possible impact on plasma and tissue concentrations of drugs in humans.

Acetamides↗

Exon skipping mutation in the COL9A2 gene in a family with multiple epiphyseal dysplasia.

Previous linkage analysis (Briggs, M.D., Choi, H.-C., Warman, M.L. et al., 1994. Genetic mapping of a locus for multiple epiphyseal dysplasia (EDM 2) to a region of chromosome 1 containing a type IX collagen gene. Am. J. Hum. Genet. 55, 678-684) in a large English family with multiple epiphyseal dysplasia established the EDM2 locus, a region of chromosome 1 containing the COL9A2 collagen gene. We now report that affected members of this family are heterozygous for a single base transversion (T-->G) at the sixth position of the intron 3 splice donor of COL9A2. The mutation leads to skipping of exon 3 during splicing, and results in a 36-nucleotide deletion in COL9A2 transcripts derived from the mutant allele. Skipping of exon 3 predicts an in-frame deletion of 12 amino acid residues within the COL3 domain of the alpha2(IX) chain. This is the fifth instance of an exon 3 deletion within the COL3 region of collagen IX heterotrimers causing the MED phenotype, as yet the only type IX collagen defect identified in this disorder. Electron microscopy (EM) of chondrocytes obtained from articular cartilage of one affected individual in the family demonstrated normal appearing rough endoplasmic reticulum (RER). In addition, the articular cartilage matrix did not show any gross abnormalities in the quantity or caliber of collagen fibrils.

Alleles↗

Hepatocyte growth factor/scatter factor in the eye.

Hepatocyte growth factor, also known as scatter factor (HGF/SF) is a multipotential cytokine which can produce a range of responses in target cells and its influence in the eye in health and disease is just beginning to be appreciated. Usually HGF/SF is synthesised by mesenchymally derived cells and targets and signals epithelial cells in a paracrine manner via their c-Met surface receptor. However, there is growing evidence for the existence of autocrine loops in a number of cell systems prominent among which are ocular cells such as the corneal endothelium, the lens epithelium, the retinal pigment epithelium (RPE) and others. Marked cellular proliferation is stimulated when activated HGF/SF is exposed to hepatocytes, renal epithelium, melanocytes and vascular endothelial cells but it is often a poor mitogen for other cell types. In target cells the cytokine promotes other bioactions such as junctional breakdown, shape change, cell scattering, directional and nondirectional migration, cell survival, invasive behaviour and/or tubule formation. These activities seem to depend on HGF/SF linking with the c-Met receptor and pathways to stimulate the various types of cytokine/receptor response are being unravelled at the present time. In corneal wound healing, HGF/SF is produced by stromal keratocytes and targets the repairing epithelium. HGF/SF is a constituent of tears, aqueous humour and vitreous humour at levels above that found in plasma although it is not clear how much is activated. Aqueous HGF/SF may well influence lens epithelial, corneal endothelial and trabecular meshwork cell survival. Vitreous levels of HGF/SF are elevated in proliferative vitreoretinopathy (PVR), where a target cell is the RPE and in proliferative diabetic retinopathy (PDR) where HGF/SF has been shown to be a major angiogenesis factor. Finally HGF/SF may be involved in the metastatic spread of tumour cells from uveal melanomata and in the formation of vascular channels in these tumours.

Animals↗

Megakaryopoiesis in vitro in myelodysplastic syndromes and acute myeloid leukaemia: effect of pegylated recombinant human megakaryocyte growth and development factor in combination with other growth factors.

Pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF) can stimulate megakaryopoiesis in vitro in some myelodysplastic syndrome (MDS) and acute myeloid leukaemia (AML) patients. We assessed PEG-rHuMGDF combined with granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage CSF (GM-CSF), interleukin 3 (IL-3), IL6, stem cell factor (SCF) or erythropoietin in 40 MDS, 33 AML and 16 normal bone marrow samples. CD61-positive cells in suspension cultures increased with PEG-rHuMGDF alone in 20/25 RA + RAS, 11/14 RAEB + RAEBt and 29/33 AML cases. Further increases when IL-3 and/or SCF were added to PEG-rHuMGDF occurred in 14/20 RA + RAS, 8/13 RAEB + RAEBt and 18/26 AML cases. CFU-Mk growth was poor overall, but could be enhanced by PEG-rHuMGDF combinations in some patients. Stimulation of megakaryopoiesis by PEG-rHuMGDF can be augmented by IL-3 and SCF in many MDS and AML patients.

Adolescent↗