Safety and immunogenicity of AS03B adjuvanted split virion versus non-adjuvanted whole virion H1N1 influenza vaccine in UK children aged 6 months-12 years: open label, randomised, parallel group, multicentre study.

OBJECTIVES: To compare the safety, reactogenicity, and immunogenicity of an adjuvanted split virion H1N1 vaccine and a non-adjuvanted whole virion vaccine used in the pandemic immunisation programme in the United Kingdom. DESIGN: Open label, randomised, parallel group, phase II study. SETTING: Five UK centres (Oxford, Southampton, Bristol, Exeter, and London). PARTICIPANTS: Children aged 6 months to less than 13 years for whom a parent or guardian had provided written informed consent and who were able to comply with study procedures were eligible. Those with laboratory confirmed pandemic H1N1 influenza or clinically diagnosed disease meriting antiviral treatment, allergy to egg or any other vaccine components, or coagulation defects, or who were severely immunocompromised or had recently received blood products were excluded. Children were grouped by age: 6 months-<3 years (younger group) and 3-<13 years (older group). Recruitment was by media advertising and direct mailing. Recruitment visits were attended by 949 participants, of whom 943 were enrolled and 937 included in the per protocol analysis. INTERVENTIONS: Participants were randomised 1:1 to receive AS03(B) (tocopherol based oil in water emulsion) adjuvanted split virion vaccine derived from egg culture or non-adjuvanted whole virion vaccine derived from cell culture. Both were given as two doses 21 days apart. Reactogenicity data were collected for one week after immunisation by diary card. Serum samples were collected at baseline and after the second dose. MAIN OUTCOME MEASURES: Primary reactogenicity end points were frequency and severity of fever, tenderness, swelling, and erythema after vaccination. Immunogenicity was measured by microneutralisation and haemagglutination inhibition assays. The primary immunogenicity objective was a comparison between vaccines of the percentage of participants showing seroconversion by the microneutralisation assay (fourfold rise to a titre of >or=1:40 from before vaccination to three weeks after the second dose). RESULTS: Seroconversion rates were higher after the adjuvanted split virion vaccine than after the whole virion vaccine, most notably in the youngest children (163 of 166 participants with paired serum samples (98.2%, 95% confidence interval 94.8% to 99.6%) v 157 of 196 (80.1%, 73.8% to 85.5%), P<0.001) in children under 3 years and 226 of 228 (99.1%, 96.9% to 99.9%) v 95.9%, 92.4% to 98.1%, P=0.03) in those over 3 years). The adjuvanted split virion vaccine was more reactogenic than the whole virion vaccine, with more frequent systemic reactions and severe local reactions in children aged over 5 years after dose one (13 (7.2%, 3.9% to 12%) v 2 (1.1%, 0.1% to 3.9%), P<0.001) and dose two (15 (8.5%, 4.8% to 13.7%) v 2 (1.1%, 0.1% to 4.1%), P<0.002) and after dose two in those under 5 years (15 (5.9%, 3.3% to 9.6%) v 0 (0.0%, 0% to 1.4%), P<0.001). Dose two of the adjuvanted split virion vaccine was more reactogenic than dose one, especially for fever >or=38 masculineC in those aged under 5 (24 (8.9%, 5.8% to 12.9%) v 57 (22.4%, 17.5% to 28.1%), P<0.001). CONCLUSIONS: In this first direct comparison of an AS03(B) adjuvanted split virion versus whole virion non-adjuvanted H1N1 vaccine, the adjuvanted vaccine, while more reactogenic, was more immunogenic and, importantly, achieved high seroconversion rates in children aged less than 3 years. This indicates the potential for improved immunogenicity of influenza vaccines in this age group. TRIAL REGISTRATION: Clinical trials.gov NCT00980850; ISRCTN89141709.

An evidence and consensus based guideline for acute diarrhoea management.

OBJECTIVE: To develop an evidence and consensus based guideline for the management of the child who presents to hospital with diarrhoea (with or without vomiting), a common problem representing 16% of all paediatric medical attenders at an accident and emergency department. Clinical assessment, investigations (biochemistry and stool culture in particular), admission, and treatment are addressed. The guideline aims to aid junior doctors in recognising children who need admission for observation and treatment and those who may safely go home. EVIDENCE: A systematic review of the literature was performed. Selected articles were appraised, graded, and synthesised qualitatively. Statements on recommendation were generated. CONSENSUS: An anonymous, postal Delphi consensus process was used. A panel of 39 selected medical and nursing staff were asked to grade their agreement with the generated statements. They were sent the papers, appraisals, and literature review. On the second and third rounds they were asked to re-grade their agreement in the light of other panelists' responses. Consensus was predefined as 83% of panelists agreeing with the statement. RECOMMENDATIONS: Clinical signs useful in assessment of level of dehydration were agreed. Admission to a paediatric facility is advised for children who show signs of dehydration. For those with mild to moderate dehydration, estimated deficit is replaced over four hours with oral rehydration solution (glucose based, 200-250 mOsm/l) given "little and often". A nasogastric tube should be used if fluid is refused and normal feeds started following rehydration. Children at high risk of dehydration should be observed to ensure at least maintenance fluid is tolerated. Management of more severe dehydration is detailed. Antidiarrhoeal medication is not indicated. VALIDATION: The guideline has been successfully implemented and evaluated in a paediatric accident and emergency department.

Determining the common medical presenting problems to an accident and emergency department.

All accident and emergency (A&E) attendances over a one year period were prospectively studied in order to determine common medical presenting problems. Data were collected on children (0-15 years) attending a paediatric A&E department in Nottingham between February 1997 and February 1998. A total of 38 982 children were seen. The diagnoses of 26 756 (69%) were classified as trauma or surgical, and 10 369 (27%) as medical; 1857 (4%) could not be classified. The commonest presenting problems reported for "medical" children were breathing difficulty (31%), febrile illness (20%), diarrhoea with or without vomiting (16%), abdominal pain (6%), seizure (5%), and rash (5%). The most senior doctor seeing these patients in A&E was a senior house officer (intern or junior resident) in 78% of cases, paediatric registrar (senior resident) in 19%, consultant (attending physician) in 1.4%, and "other" in 2.6%. Guidelines developed for A&E should target the commonest presenting problem categories, six of which account for 83% of all medical attendances, and be directed towards senior house officers.

Accounting for overlap? An application of Mezzich's kappa statistic to test interrater reliability of interview data on parental accident and emergency attendance.

STUDY RATIONALE: The number of interview studies with service users is rising because of growth in health services research. The level of agreement between multiple interview data coders requires statistical calculation to support results. Basic kappa statistics are often used but this depends on having mutually exclusive data. Researchers should be aware that this is not valid when an interview word or paragraph can be coded into more than one category. The 'proportional overlap' kappa extension by Mezzich et al. (1981, Journal of Psychiatric Research 16, 29-39) has been investigated as an original solution. OBJECTIVES: To assess the level of agreement beyond chance between several raters of interview data by applying the 'proportional overlap' kappa statistic by Mezzich et al. to verbal interview data. The clinical area investigated was child attendance at an Accident and Emergency Department, where parental attendance experiences have been under-explored. METHODS: Two researchers using a coding schedule coded a random sample of interview transcripts. These data were applied to Mezzich's procedure; coder 1 notes that a paragraph refers to category A and B but coder 2 notes A, B and C. The total agreement overlap in this case was 0.66 because two actual agreements out of three possible agreements were made. This was repeated for each paragraph and divided by the number of coding pairs. All agreement values were summed then subsequently divided by the total number of paragraphs to get Po (total number of observed agreements) and by the total number of coding pairs to get Pe (total number of agreements by chance alone). Po and Pe were used in the basic kappa formula to assess interview coding reliability. RESULTS: The overall mean Po was 0.61, the mean Pe was 0.32, with a kappa score of 0.43; a moderate level of agreement which was statistically significant (t=4.8, P < 0.001, d.f.=23). CONCLUSION: Mezzich's procedure may be applied to interview data to calculate agreement levels between several coders.

Teaching smoking cessation skills to senior medical students: a block-randomized controlled trial of four different approaches.

BACKGROUND: Medical practitioners have considerable untapped potential to assist patients in stopping smoking. However, marked deficits have been found in the amount and type of training medical practitioners receive in smoking cessation counseling with little attention paid to determination of effective training methods. METHOD: A randomized controlled trial was conducted to examine the relative effectiveness of four different educational programs in teaching smoking cessation skills to 5th-year medical students in an Australian medical school. The four programs comprised: (a) a traditional didactic lecture mode (control group), (b) audio feedback through the use of audiotaped role plays, (c) role plays with peer feedback, and (d) video feedback. Students' smoking cessation intervention skills were assessed prior to training and at the end of term via videotaped interviews with simulated patients. RESULTS: Senior medical students demonstrated significantly improved skills in smoking intervention when exposed to any of the educational approaches other than traditional didactic teaching. No overall differences in smoking intervention skills were found between the three experimental training methods. CONCLUSIONS: Specific training in smoking cessation techniques is necessary to increase the intervention skills of medical students. Traditional teaching methods are ineffective in developing smoking cessation intervention skills. Enhanced teaching, of an appropriate nature, at undergraduate and postgraduate levels is needed.

Smoking-related knowledge and attitudes of senior Australian medical students.

OBJECTIVE: To assess the smoking-related knowledge and attitudes of senior medical students and to compare knowledge and attitude changes in students exposed to four different smoking cessation skills training interventions. DESIGN: A survey questionnaire, assessing knowledge and attitudes, was administered pre- and post-intervention for each of the four intervention conditions. SUBJECTS: A cohort of 219 fifth-year medical students at the University of Sydney. INTERVENTIONS: Students were randomised into one of four intervention conditions: (1) a traditional didactic lecture mode (control group); (2) the use of role plays and audiotaped feedback; (3) role plays with peer feedback; and (4) video feedback. MAIN OUTCOME MEASURES: Knowledge on morbidity and mortality associated with smoking, intervention strategies, intervention effectiveness, and cessation practices; anticipated clinical behaviour related to smoking; and attitudes towards medical practitioner involvement in smoking cessation. RESULTS: Smoking knowledge was significantly greater at post-test (mean unweighted scores of 69% before and 74% after intervention). All groups had improved knowledge levels at post-test. However, after controlling for pre-test differences, the control group, video feedback, and peer feedback groups were found to have improved significantly over the audio feedback group. Scores were higher on items related to morbidity and mortality and intervention effectiveness than for items on intervention strategies and cessation practices. Positive student attitudes towards their role in smoking cessation were also found. There was an almost universally held view that doctors can have a significant impact on reducing smoking levels. Although most students perceived smoking intervention to be a worthwhile activity, they remained pessimistic about the ease with which patients' smoking behaviour could be changed. CONCLUSIONS: Positive smoking cessation knowledge changes can be readily achieved through training. However, specific smoking cessation training is needed for medical trainees to develop appropriate skills and strategies. Attention to particular weaknesses related to specific intervention strategies and cessation practices is required to develop competence in this area and to maximise the chances of new medical graduates fully using the opportunities available to them.

Neurons of the peripheral nervous system express thymidine phosphorylase.

Platelet-derived endothelial cell growth factor (PD-ECGF) is an angiogenic factor which recently has been shown to be identical to thymidine phosphorylase. We describe here, high levels of expression of PD-ECGF/thymidine phosphorylase in neurons of the peripheral nervous system (PNS) but very little in the central nervous system (CNS). Monoclonal and polyclonal antibodies were used for the staining of sections of dorsal root ganglia, sympathetic cervical ganglia and the enteric plexus as well as the brain and spinal cord. In addition, in situ hybridisation confirmed the results of immunohistochemistry. The possible role of thymidine phosphorylase in the PNS is discussed.

Expression of platelet-derived growth factor (PDGF) and PDGF alpha- and beta-receptors in the peripheral nervous system: an analysis of sciatic nerve and dorsal root ganglia.

Previous studies have shown that cultured Schwann cells secrete platelet-derived growth factor (PDGF) and express PDGF receptors which transmit a mitogenic response particularly when their levels are upregulated by elevation of intracellular cAMP. In this study the expression of PDGF and PDGF alpha- and beta-receptors in the peripheral nervous system (PNS) has been examined by studying dorsal root ganglia and sciatic nerve. Using the monoclonal anti-PDGF antibody, PGF-007, relatively high levels of PDGF were detected in cells of the neonatal rat dorsal root ganglia and sciatic nerve. The location and morphology of these cells indicated that they were Schwann cells while neurons of the dorsal root ganglia were less strongly labeled. The levels in Schwann cells declined during the first postnatal weeks. In the adult rat, low levels of PDGF were detected on myelinated nerve fibers while unmyelinated fibers continued to express higher levels of PDGF. Antisera specific for the PDGF alpha- and beta-receptor revealed high levels of both receptors in the neonatal rat PNS. In the adult rat peripheral nerve both receptors were detectable in unmyelinated nerve fibers. The PDGF beta-receptor, but not the alpha-receptor, was detected at low levels on myelinated nerve fibers. Teased nerve preparations, as well as freshly dissociated sciatic nerve cells, were used to substantiate the findings in frozen tissue sections. Neurons of the dorsal root ganglion expressed PDGF and PDGF alpha- and beta-receptors in all the stages of postnatal development examined. These results indicate that PDGF might play a role in the development of the PNS and in maintenance of peripheral neurons.

Interaction between cAMP elevation, identified growth factors, and serum components in regulating Schwann cell growth.

Most previous studies on Schwann cell proliferation in vitro have used serum-containing media. This complicates the analysis of agents required for cell division since serum contains an ill-defined mixture of hormones and growth factors. Serum-free medium has therefore been used to analyse the response of Schwann cell to previously identified Schwann cell mitogens. Serum factors were not necessary for DNA synthesis in response to platelet-derived growth factor, basic fibroblast growth factor, or glial growth factor, provided they were used in combination with forskolin to elevate intracellular cAMP. Transforming growth factor beta 1, a Schwann cell mitogen in serum, was not mitogenic under these conditions. Neither the growth factors nor forskolin were effective when used alone. Growth control was analysed further using long-term cultured Schwann cells that had spontaneously immortalized. Measurements of endogenous cAMP levels in short- and long-term Schwann cells revealed that long-term cells had two to three times higher basal cAMP levels. As predicted by these findings, platelet-derived growth factor, basic fibroblast growth factor, and glial growth factor stimulated DNA synthesis in long-term cells without requiring costimulation by agents which elevate cAMP (while transforming growth factor beta 1 had no effect).(ABSTRACT TRUNCATED AT 250 WORDS)

Spontaneous immortalisation of Schwann cells in culture: short-term cultured Schwann cells secrete growth inhibitory activity.

In the developing peripheral nerve, Schwann cells proliferate rapidly and then become quiescent, an essential step in control of Schwann cell differentiation. Cell proliferation is controlled by growth factors that can exert positive or inhibitory influences on DNA synthesis. It has been well established that neonatal Schwann cells divide very slowly in culture when separated from neurons but here we show that when culture was continued for several months some cells began to proliferate rapidly and non-clonal lines of immortalised Schwann cells were established which could be passaged for over two years. These cells had a similar molecular phenotype to short-term cultured Schwann cells, except that they expressed intracellular and cell surface fibronectin. The difference in proliferation rates between short- and long-term cultured Schwann cells appeared to be due in part to the secretion by short-term cultured Schwann cells of growth inhibitory activity since DNA synthesis of long-term, immortalised Schwann cells was inhibited by conditioned medium from short-term cultures. This conditioned medium also inhibited DNA synthesis in short-term Schwann cells stimulated to divide by glial growth factor or elevation of intracellular cAMP. The growth inhibitory activity was not detected in the medium of long-term immortalised Schwann cells, epineurial fibroblasts, a Schwannoma (33B), astrocytes or a fibroblast-like cell-line (3T3) and it did not inhibit serum-induced DNA synthesis in epineurial fibroblasts, 33B cells or 3T3 cells. The activity was apparently distinct from transforming growth factor-beta, activin, IL6, epidermal growth factor, atrial natriuretic peptide and gamma-interferon and was heat and acid stable, resistant to collagenase and destroyed by trypsin treatment. We raise the possibility that loss of an inhibitory autocrine loop may contribute to the rapid proliferation of long-term cultured Schwann cells and that an autocrine growth inhibitor may have a role in the cessation of Schwann cell division that precedes differentiation in peripheral nerve development.

Schwann Cells Secrete a PDGF-like Factor: Evidence for an Autocrine Growth Mechanism involving PDGF.

We have investigated the influence of platelet-derived growth factor (PDGF) in peripheral nervous system gliogenesis using two types of Schwann cell cultures. Short-term Schwann cell cultures grow very slowly, but when maintained in culture for several months the division rate of some cells increases, and cell lines can be established. We show that Schwann cells in both short- and long-term culture possess PDGF receptors and synthesize DNA in response to PDGF. Competitive binding experiments show that Schwann cells express mainly PDGF beta-receptors and respond better to PDGF-BB than to PDGF-AA. Conditioned media from short- and long-term Schwann cell cultures contain PDGF-like mitogenic activity, and anti-PDGF immunoglobin partially inhibits DNA synthesis in long-term Schwann cell cultures. Antibody neutralization experiments and Northern blot analyses both indicate that the predominant PDGF isoform in these cultures is PDGF-BB. PDGF-like activity is also detected in extracts of rat sciatic nerve. Taken together, these results suggest that PDGF-BB may stimulate Schwann cell proliferation in an autocrine manner during normal development.

Transforming growth factor-beta and gamma-interferon have dual effects on growth of peripheral glia.

The influence of transforming growth factor-beta (TGF-beta) and gamma-interferon on DNA synthesis in Schwann cells and enteric glia in culture has been studied. TGF-beta stimulated the DNA synthesis of short-term (less than 2 weeks in culture) Schwann cells, whereas gamma-interferon was ineffective. The stimulatory effect of TGF-beta was additive to the stimulation of DNA synthesis due to axonal membrane fragments. In contrast to their effect on short-term Schwann cells, both TGF-beta and gamma-interferon inhibited DNA synthesis in enteric glial cells and in long-term (over 3 months in culture) Schwann cells. When short-term Schwann cells were stimulated to divide by axolemma or glial growth factor, gamma-interferon did not inhibit this enhanced DNA synthesis although it suppressed DNA synthesis induced by cAMP analogues. These results raise the possibility that TGF-beta and gamma-interferon might have a role in controlling glial proliferation during development and/or regeneration of the peripheral nervous system.

Control of peripheral glial cell proliferation: enteric neurons exert an inhibitory influence on Schwann cell and enteric glial cell DNA synthesis in culture.

Neuronal membranes from rat dorsal root ganglia provide a mitogenic signal to cultured Schwann cells and it has been suggested this is an important factor in regulating Schwann cell numbers during development. In this study, the influence of enteric neurons on the DNA synthesis of both Schwann cells and enteric glia has been investigated as well as the effect of axonal membrane fractions (axolemma) on enteric glia. The proliferation rate of rat Schwann cells and enteric glia was assessed in culture using [3H]thymidine uptake and autoradiography in combination with immunolabelling to identify cell types. When purified rat Schwann cells were co-cultured with guinea pig enteric neurons, their DNA synthesis rate was reduced compared with control cultures of pure Schwann cells or Schwann cells not close to neurites or neuronal cell bodies. Nevertheless, in accordance with previous findings that sensory neurons stimulate Schwann cell division, these Schwann cells increased their DNA synthesis rate when in contact with neurites from purified guinea pig or adult rat dorsal root ganglion neurons and on exposure to bovine axolemmal fractions. The enteric neurons also suppressed the DNA synthesis of enteric glia in co-cultures of purified enteric neurons and enteric glia, while bovine axolemma stimulated their DNA synthesis. These results indicate that a mitotic inhibitory signal is associated with enteric neurons and can exert its effect on both Schwann cells and enteric glia, and that enteric glia, like Schwann cells, are stimulated to divide by axolemmal fractions. It thus seems possible that during development glial cell numbers in the peripheral nervous system may be controlled by both positive and negative regulators of cell growth.

Type I collagen preparations inhibit DNA synthesis in glial cells of the peripheral nervous system.

The mechanisms underlying cessation of glial proliferation in the developing peripheral nervous system are obscure. One possibility, as yet little explored, is that mitotic inhibitory signals play a part in regulating glial cell numbers. In this study we demonstrate that type I collagen preparations from several different sources can inhibit the rate of DNA synthesis in purified populations of enteric glia and both short-term and long-term secondary Schwann cells in dissociated cell cultures. When these cells are grown on gelled or dried type I collagen substrata, they proliferate at substantially lower rates than on polylysine substrata. In contrast, type III or V collagen preparations do not inhibit glial DNA synthesis and laminin, fibronectin, type IV collagen, and secreted matrix from bovine corneal endothelial cells all stimulate thymidine incorporation. The inhibitory effect is not observed with heat denatured type I collagen preparations, but is seen equally in serum-containing medium, in medium containing fibronectin-free serum, or in serum-free medium, suggesting that the interaction of collagen with the cells requires structurally intact collagen molecules and does not occur via intermediary linkage to fibronectin. The inhibition on collagen is accompanied by a shape change from a more flattened morphology to a narrow spindle form. The labeling index of a rat Schwannoma cell line, 33B, is not inhibited on type I collagen substrata. These results demonstrate that type I collagen preparations inhibit the DNA synthesis levels of early postnatal peripheral glial cells in vitro. It remains to be determined whether this effect occurs via direct collagen-cell membrane interactions or whether it depends on accessory molecules, perhaps present in the collagen preparations themselves, since these are not purified to absolute homogeneity.

Control of peripheral glial cell proliferation: a comparison of the division rates of enteric glia and Schwann cells and their response to mitogens.

The enteric nervous system comprises neurons and a relatively homogeneous population of glial cells, which differ considerably from those found in other parts of the peripheral nervous system and resemble more closely astrocytes from the central nervous system. It provides a simple model system for the study of neuron/glial interactions and glial cell development. In this study the proliferation rates of purified populations of enteric glia and Schwann cells and their response to several mitogens in vitro were compared. Enteric glial cells divided at a much higher rate than Schwann cells in both serum-containing and serum-free media. This difference in their basal proliferation rates was the major difference seen between the two cell types. Both cell populations were stimulated to divide by fibroblast growth factor and glial growth factor but not by epidermal growth factor. Enteric glial cells and Schwann cells proliferated at a greater rate on a basement membrane-like extracellular matrix produced by corneal endothelial cells, laminin, and fibronectin than on poly-L-lysine-coated glass coverslips. The magnitude of stimulation was greater for Schwann cells, presumably due to their lower basal division rates. Like Schwann cells, enteric glial cells were stimulated to divide by two agents which elevate intracellular cAMP, cholera toxin, and dibutyryl cAMP.

Postnatal development of rat peripheral nerves: an immunohistochemical study of membrane lipids common to non-myelin forming Schwann cells, myelin forming Schwann cells and oligodendrocytes.

Interest in the role of membrane lipids in Schwann cell function prompted this study of lipid antigens on myelin- and non-myelin forming Schwann cells. Using the monoclonal antibodies 07, which recognises galactocerebroside, 08, 09 and 011, the distribution and time course of expression of the 4 membrane lipids have been determined in Schwann cells of the rat sciatic nerve and sympathetic trunk, derived from 1-60-day-old rats. The proportion of Schwann cells binding each monoclonal antibody was found by dissociating the nerves and allowing 3 h for the cells to attach to coverslips, prior to double label immunofluorescence, using the monoclonal antibody in conjunction with antibodies to S100 as a general Schwann cell marker, or P0 to distinguish cells which had formed myelin. All 4 lipid antigens were expressed by myelin forming Schwann cells, appearing just before, or at the time that the cells started to form myelin. Only 011 was restricted to myelin forming Schwann cells. Non-myelin forming Schwann cells expressed 07, 08 and 09. In the cervical sympathetic trunk, the developmental expression of these 3 lipids was essentially complete by postnatal day 20, whereas in the sciatic nerve, expression was not complete until days 40-60. The results show that the biochemical maturation in non-myelin forming Schwann cells differs greatly between different nerves, and may not be completed until several weeks postnatally. The results also demonstrate that in addition to galactocerebroside, other similarities exist in the lipid composition of myelin and the plasma membrane of non-myelin forming Schwann cells since the lipids defined by 08 and 09 antibodies are found among both Schwann cell variants.

Search for antibodies to galactocerebroside in the serum and cerebrospinal fluid in human demyelinating disorders.

To determine if galactocerebroside (GalC) is a target antigen in the human demyelinating disorders multiple sclerosis, Guillain-Barré syndrome, and chronic demyelinating inflammatory polyneuropathy, we examined the serum and cerebrospinal fluid from patients with these disorders and from control subjects using four assay systems. In none of these assays could we detect significant differences in anti-GalC antibody titer between patients with demyelinating diseases and normal subjects or patients with other neurological disorders. Our data suggest that there is no humoral immune response to GalC in human demyelinating disorders.

Fibroblast growth factor is a mitogen for oligodendrocytes in vitro.

The effect of fibroblast growth factor (FGF) on oligodendrocyte development has been studied using dissociated mixed brain cells, cultured in a previously described serum-free medium. A greater number of galactocerebroside-positive oligodendrocytes could be demonstrated after 7 days in the presence of FGF than in control values. Using combined immunofluorescence and autoradiography an increased [3H]thymidine incorporation by galactocerebroside-positive oligodendrocytes was demonstrated after various times of exposure to FGF.