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Biomedical subjects

A Kemp

Publications and source records attributed to A Kemp.

At least 73 records · Page 4Linked to original sources
PubMed1998

Studies on an outbreak of Wesselsbron virus in the Free State Province, South Africa.

In early March 1996, Wesselsbron (WSL) virus caused mortality among lambs on a farm near Bultfontein in the northern Free State Province, South Africa. Mosquito collections were therefore undertaken from 27 March to 1 April to collect floodwater Aedes mosquitoes for attempts at virus isolation. In all, 4,732 floodwater Aedes were tested; 5 WSL, 1 Middelburg (MID), and 5 unidentified viruses were isolated from 3,052 Aedes (Neomelaniconion) mcintoshi/luridus (minimum infection rate [MIR] for WSL = 1.63) and 5 WSL, 1 MID, and 3 unidentified viruses from 1,478 Aedes (Ochlerotatus) juppi/caballus (MIR for WSL = 3.38). One of the authors developed WSL fever on 3 April; WSL virus was isolated from his serum, and he developed a titer of 1:640 in the hemagglutination inhibition (HI) test and became IgM positive against WSL virus. Among a sample of 44 sheep bled on 4-5 September, 59% were antibody positive by the HI test against WSL and 48% against MID viruses. Mosquito collecting was restricted to 2 discrete, shallow, grassy depressions that were the main floodwater Aedes breeding sites on the farm so they will be investigated further as possible foci of transovarial transmission of WSL and MID viruses.

Aedes↗
PubMed1997

Safety of surfaces and equipment for children in playgrounds.

BACKGROUND: The safety of playgrounds is important to protect children from injury, but studies are mostly done mainly under laboratory conditions without epidemiological data. We investigated the safety of different playground surfaces, and types and heights of equipment in public playgrounds in the City of Cardiff, UK. METHODS: We did a correlational study of 330 children aged between 0 and 14 years. All children were hurt when playing in playgrounds in Cardiff and presented to the Accident and Emergency Department in Cardiff Royal Infirmary during summer (April to September) 1992 and 1993, and the whole of 1994. We studied the children's hospital records to establish the type of injury and interviewed their parents to find out the playground and type of equipment involved. The main outcome measures were the number of children injured whilst playing, and injury rates per observed number of children on different surfaces, types, and heights of equipment. FINDINGS: Children sustained significantly more injuries in playgrounds with concrete surfaces than in those with bark or rubberised surfaces (p < 0.001). Playgrounds with rubber surfaces had the lowest rate of injury, with a risk half that of bark and a fifth of that of concrete. Bark surfaces were not significantly more protective against arm fractures than concrete. Most injuries were equipment related. Injury risk due to falls from monkey bars (suspended parallel bars or rings between which children swing) was twice that for climbing-frames and seven times that for swings or slides. The height of the equipment correlated significantly with the number of fractures (p = 0.005) from falls. INTERPRETATION: Rubber or bark surfacing is associated with a low rate of injuries and we support their use in all public playgrounds. Bark alone is insufficient, however, to prevent all injuries, particularly arm fractures. Rubberised impact-absorbing surfaces are safer than bark. We believe that playing on monkeys bars increases the risk of injury in playgrounds and that they should generally not be installed. Safety standards should be based on physical and epidemiological data. Our data suggest that the proposed raising of the maximum fall height from 2.5 m to 3.0 m in Europe is worrying.

Accidental Falls↗
PubMed1997

The spectrum of primary immunodeficiency disorders in Australia.

BACKGROUND: Primary immunodeficiency disorders (PIDs) are uncommon conditions that require specialized immunologic services for diagnosis and management. It is difficult to estimate the prevalence of these disorders from routinely collected health statistics. OBJECTIVE: We attempted to describe the prevalence of PID in Australia and the requirements for specific therapies, such as intravenous immunoglobulin, ascertained from a national register of PID. METHODS: A national longitudinal cross-sectional survey of patients with PID under the care of clinical immunologists was established by the Australasian Society of Allergy and Clinical Immunology in 1990. Details of diagnosis and therapy were provided for patients with major PIDs including symptomatic IgA, IgG subclass, and complement deficiencies. Subjects with asymptomatic IgA deficiency were not included. The clinical features of the first 500 cases enrolled in the register were analyzed. RESULTS: The most frequent type of PID was predominant antibody deficiency (71%). Common variable immunodeficiency, usually first seen as an antibody deficiency, was the single most common disorder with an estimated prevalence of 0.77/100,000 in the general population. Other types of PID were infrequent, and of these, severe combined immunodeficiency accounted for 5.2% of cases. The estimated prevalence of all forms of chronic granulomatous disease was 0.08/100,000. The national prevalence of all PID cases ascertained from the register was 2.1/100,000, with variation between the larger states ranging from 1.18 to 4.57/100,000. Half (247) of the patients were receiving intravenous immunoglobulin therapy with a median duration of care of 5 to 9 years for the different antibody deficiencies. There was also variation in the patterns of intravenous immunoglobulin use across the country. No new forms of PID were encountered. CONCLUSION: This study highlights the requirement for the continuing provision of immunoglobulin as replacement therapy for these patients. In addition, the register documents a cohort of patients with PID whose long-term response to current therapy can be evaluated prospectively.

Adolescent↗
PubMed1997

Childhood accidents: epidemiology, trends, and prevention.

Accidents are the most common cause of death in children over one year of age. Prevention remains a high priority. We have reviewed the current epidemiology of childhood accidents and their prevention, and made recommendations for the future. In 1992, 559 children died in United Kingdom as a result of an accidents--240 from road traffic accidents and 100 from burns and scalds. Every year 50 children drown. Accidents cause significant disability to children. Many children, up to one in four of the population in urban areas, attend accident and emergency departments, and 5-10% of these are admitted to hospital. Accident risk factors include low social class, psychosocial stress, an unsafe environment, and child developmental disorders. Research has shown that prevention is best achieved by making the child's environment safer, often through legislation. Insufficient resources have been put into both research into childhood injuries and preventive work in communities. Collaboration between health authorities, NHS trusts, local authorities and community networks is vital if success is to be achieved. A national safety agenda for children would focus the attention that this problem deserves.

Accident Prevention↗
PubMed1996

A combination of CD34 selection and complement-mediated immunopurging (anti-CD15 monoclonal antibody) eliminates tumor cells while sparing normal progenitor cells.

Autologous bone marrow transplantation (ABMT) for acute myeloid leukemia (AML) in first complete remission (CR) results in a prolonged disease-free survival (DFS) of 34%-57%. Relapse of the underlying disease is the major cause for failure of ABMT. Relapse can result fom tumor cells either surviving in the patient or reinfused in the autograft. Genetic marking of autografted cells has demonstrated that transplanted cells contribute to relapse. This finding supports the use of purged autografts. Several purging techniques have been used. Immunologic purging using the monoclonal antibody (mAb) PM-81 (anti-CD15) has been used by our center with a long-term DFS in 50% of AML patients. PM-81 reacts with 90% of AML patients, and we have used it for over 10 years. We have investigated a two-stage purging technique involving initial selection for CD34+ cells followed by mAb purging in bone marrow (BM) and peripheral blood stem cell (PBSC) harvests. This method achieved up to a 7 log diminution in leukemic cells and 1-4 log reduction in CD15+ cells, without a significant loss of hematopoietic progenitor cells. This double-purging technique has the advantages of cytoreduction, elimination of CD34- leukemic cells, and possible improvement in the clinical efficacy of purging by concentrating for CD34+ cells. Cytoreduction by CD34 enrichment followed by purging may facilitate the use of PBSC transplants in AML.

Antibodies, Monoclonal↗
PubMed1996

Preliminary observations on possible premalignant changes in bone marrow adjacent to worn total hip arthroplasty implants.

Previous epidemiologic studies have suggested that there may be a risk of malignancy, especially lymphoma and leukemia, after joint replacement, but the followup has been relatively short. This is a preliminary study to see if there is any biologic basis for such a risk. Blood and bone marrow samples from 71 patients at revision arthroplasty of a loose or worn prosthesis and 30 control patients at primary arthroplasty were analyzed with cytogenetic techniques and molecular biology. There was a higher chromosomal aberration rate in cells adjacent to the prosthesis at revision surgery compared with iliac crest marrow from the same patients or with femoral bone marrow at primary arthroplasty. Clonal expansion of lymphocytes without a serum paraprotein was seen in 2 of 21 patients at revision arthroplasty performed more than 10 years after primary arthroplasty. The results of this preliminary study suggest that future epidemiologic studies should concentrate on patients with longer postoperative intervals to see if there is any risk that would be pertinent to a young patient at primary arthroplasty.

Aged↗
PubMed1996

Treatment of hypogammaglobulinaemia with intravenous immunoglobulin, 1973-93.

AIMS: To review the results of long term high dose intravenous immunoglobulin treatment. METHODS: 162 treatment years in 18 patients with hypogammaglobulinaemia who received intravenous immunoglobulin treatment between 1973 and 1993 were reviewed. RESULTS: A mean dose of 0.42 g/kg immunoglobulin resulted in a mean trough IgG concentration on the 23.5th centile for age. The subjects enjoyed a good standard of health. Infection rates were similar to the general paediatric population and a similar pattern of infections occurred. There were only 0.06 episodes of pneumonia and 0.11 hospital admissions per year of treatment. The development of chronic pulmonary disease was significantly related to trough IgG concentrations less than the 10th centile (p < 0.009), however, this developed in only two children after the start of treatment. All children had normal growth parameters. Adverse reactions to immunoglobulin infusions reduced from 9.1% to 0.8% after the introduction of low pH modified intravenous immunoglobulin in 1986. Although minor, transient increases in liver transaminase values were common; none of the 11 patients tested by hepatitis C polymerase chain reaction were positive. CONCLUSION: Children with hypogammaglobulinaemia who are receiving replacement treatment grow normally and have an infection rate similar to that of non-immunodeficient children. No evidence of transmission of hepatitis C virus by the Commonwealth Serum Laboratories immunoglobulin was found.

Agammaglobulinemia↗
PubMed1995

Long-term expression of the glucocerebrosidase gene in mouse and human hematopoietic progenitors.

Gaucher disease (GD), one of the most common inherited metabolic disorders, is an excellent candidate for gene therapy using hematopoietic stem cells as targets. Animal models have demonstrated the feasibility of introducing the human glucocerebrosidase (GC) gene into hematopoietic progenitors with long term expression using a variety of retroviral vectors. We have previously demonstrated the expression and integration of the human GC gene in mouse hematopoietic progenitors and their progeny 4-8 months post transplant in primary recipients using the retroviral vector MFG-GC. We now demonstrate enzyme expression in peripheral blood lymphocytes of secondary recipients more than 12 months post transplantation. We also show a transduction efficiency of up to 95% in colony forming unit-granulocyte macrophage (CFU-GM) colonies generated from transduced CD34+ cells from a variety of sources, using a centrifugation promoted infection protocol. Transduction has also been documented in long term culture initiating cells (LTCIC) from the same transduced CD34+ cells. These data indicate efficient transduction of mouse hematopoietic progenitors as well as human CD34+ cells using the retroviral vector MFG-GC.

Animals↗
PubMed1995

Efficient retroviral mediated transfer of the glucocerebrosidase gene in CD34+ enriched umbilical cord blood human hematopoietic progenitors.

Obtaining efficient transfer of a normal gene and its sustained expression in self-renewing hematopoietic stem cell populations is a central concern for gene therapy initiatives. Potentially, 10(8) to 10(9) CD34+ enriched cells per patient will be required for transduction and subsequent reimplantation. These studies present an efficient method for the transduction of human CD34+ cells that can be used in a clinical study of gene transfer. The method uses a centrifugation-enhanced technique for the retroviral-mediated transfer of the normal human glucocerebrosidase (GC) gene to human CD34+ enriched umbilical cord blood cells (CB). Previous studies had described high expression of GC in CD34+ enriched cells but had not reported transduction efficiency in the progenitor population specifically. The data demonstrate an average transduction efficiency in the progenitor cell population of 50% as measured by polymerase chain reaction (PCR) for the integrated GC-cDNA in clonogenic cells. Measurements of enzyme activity comparing transduced and nontransduced fractions at 6 days posttransduction indicate an average enzyme increase of six-fold over normal background levels. PCR of colony forming units-granulocyte/macrophage (CFU-GM) plated at 6 weeks from long-term culture-initiating cell (LTC-IC) cultures also indicates transfer of the transgene to early progenitor cells. Finally, experiments were carried out with the human erythroleukemia cell line, TF-1, to estimate the durable expression of the transgene. Enzymatic activities in transduced TF-1 cultures remained at 30-fold above the activity of nontransduced controls. The expression persisted for 6 weeks in culture. These studies demonstrate efficient transduction of early progenitor cells and sustained expression of the transgene in cell cultures.

Antigens, CD34↗
PubMed1995

Cytokine mobilization of peripheral blood stem cells in patients with Gaucher disease with a view to gene therapy.

As clinical trials for gene therapy in Gaucher disease (GD) begin, questions regarding the biology of the hematopoietic stem cell in this disease remain unanswered. This study demonstrates the ability to mobilize and collect CD34+ cells in three patients with the disorder. Our RAC/FDA-approved clinical trial utilizes mobilized peripheral blood stem cells (PBSC) as the target cells for gene transfer. In this approach, a white blood cell fraction is collected by apheresis, enriched for CD34+ cells, and transduced with a retroviral vector carrying the glucocerebrosidase (GC) gene. Transduced cells from the patient with activity corrected to at least normal levels will be returned to the patient without myelosuppressive therapy. We report here the effect of cytokines in mobilizing PBSC in three patients with GD. Two (patients 1 and 2) were given granulocyte colony-stimulating factor (G-CSF) at a dose of 5 micrograms/kg/d and one (patient 3) was given 10 micrograms/kg/d for 10 days. Leukaphereses were done daily for 5 days and the products enriched for CD34+ cells using the clinical Ceprate (CellPro) column. The CD34+ cells in all fractions were monitored daily during mobilization and leukaphereses. Subset analysis for the expression of Thy-1, CD38, HLA-DR, and CD33 on the CD34+ cells was performed. An increase in CD34+ cells in the peripheral blood was noted from day 5 onward (up to a six-fold increase). Up to a 625-fold enrichment in CD34+ cells in the apheresis product was noted using the clinical Ceprate column. Totals of 1.2, 3.5, and 2.1 x 10(6) CD34+ cells/kg were collected in the three patients. A diminution in the percent of CD34+/Thy-1+ cells was noted with enrichment. In vitro retroviral transduction of the CD34-enriched cells using centrifugation promoted transduction protocol previously described (Bahnson AB et al., Centrifugal enhancement of retroviral-mediated gene transfer. Journal of Virology Methods 54:131, 1995) and modified for clinical use, demonstrated a mean transduction efficiency of 37% (range 8.3-87.1%) in clonogenic cells and up to 50% in long-term culture-initiating cells (LTC-IC) at week 6. Significantly, we have been able to achieve up to a 50-fold increase in the level of GC above deficient levels in the patients' CD34+ enriched cells when maintained in vitro in culture. The study demonstrates that up to a six-fold increase in CD34+ cells in the PB can be achieved with cytokines in patients with GD. CD34+ cells can be collected in numbers sufficient for conventional transplantation and transduced efficiently in vitro. In gene therapy trials for genetic disorders to date, myelosuppressive therapy is not advocated. The clinical trial will demonstrate whether this number of transduced CD34+ cells will be adequate for competitive engraftment of genetically corrected PBSC.

Adult↗
PubMed1994

Measles immunisation in children with allergy to egg.

OBJECTIVE: To examine the occurrence of adverse reactions to measles vaccine given as a single dose to children with egg allergy, and to determine if the administration of single dose to children with a positive result in an intradermal skin prick test with the vaccine is associated with adverse reactions. DESIGN: Review of results of immunisation and prospective study of 96 consecutively presenting children given intradermal skin testing with the vaccine. SETTING: Children's allergy centre. SUBJECTS: 410 children sensitive to egg referred to the allergy unit for advice about measles immunisation. MAIN OUTCOME MEASURES: Nature and severity of reactions associated with the administration of measles vaccine. RESULTS: All children had a positive result in a skin prick test with egg white, and five had a positive result in a skin prick test with vaccine. Of 96 consecutive children, 46 had a positive result in an intradermal test with vaccine. After immunisation with a full dose (0.5 ml) of vaccine adverse reactions were associated with a mild reaction in four children, none of whom required treatment. Only one of the 46 children with a positive result in an intradermal vaccine skin test had a reaction associated with vaccine administration. None of the children with a positive result in a skin prick test with measles vaccine reacted to the vaccine. The rate of minor reactions to the vaccine not requiring treatment was 0.98% (95% confidence interval 0.27% to 2.48%) and serious reactions requiring treatment was 0% (0% to 0.9%). CONCLUSION: Children with IgE mediated allergic reactions to egg protein should be investigated and managed by practitioners with special knowledge in this subject. Measles immunisation should be performed in a setting where any adverse reactions can be dealt with appropriately. Skin tests and measles vaccine and desensitisation are not necessary.

Child, Preschool↗
PubMed1994

Is speech temporally segmented? Comparison with temporal segmentation in behavior.

Phrase durations in spoken German and Korean were examined for temporal segmentation like that in behavior. Lines of poetry, which may be regarded as semantic units equivalent to action units in behavior, were found to be temporally segmented but, unlike behavior, there is a significant effect of language/culture on segment length. The lengths of the pauses made between lines while reading poetry were used to define possible semantic segments in reading prose, retelling a story, free speech, and telephone messages. No temporal segmentation was found, each situation resulting in a different distribution of phrase durations. These results are discussed in terms of a possible evolution of language from the motor system.

Adult↗
PubMed1994

Production and secretion of interferon-gamma (IFN-gamma) in children with atopic dermatitis.

IFN-gamma is known to be a major inhibitor of IgE synthesis in vitro. Recent studies demonstrating reduced production of IFN-gamma in children and adults with atopic dermatitis and elevated serum IgE suggest a similar role for this cytokine in vivo. The reasons for this reduced IFN-gamma production are not known. One possibility is that atopic individuals have a reduced population of cells producing IFN-gamma in vivo. Using a fluorescence-labelled antibody to detect intracellular IFN-gamma, the percentage of IFN-gamma-producing cells was determined in children with atopic dermatitis and in non-atopic controls. Children with atopic dermatitis had a greater percentage of IFN-gamma-producing cells in unstimulated cultures compared with controls, indicating in vivo activation of lymphocytes in the atopic group. This could reflect the significant degree of inflammation present in these children, or the presence of bacterial infection or colonization. Although secretion of IFN-gamma after stimulation with phorbol myristate acetate (PMA)/Ca was significantly lower in children with atopic dermatitis compared with controls, the percentage of IFN-gamma-producing cells in the stimulated cultures from this group was equivalent to controls. This demonstrates that the reduced ability of atopic children to secrete IFN-gamma in vitro does not relate to a lack of IFN-gamma-producing cells, but to a difference in the regulation of IFN-gamma production beyond the stage of signal transduction.

Adolescent↗
PubMed1994

Patterns of scald injuries.

OBJECTIVES: To describe common patterns of bath water scald injuries in children, to examine differences between accidental and non-accidental bath water scalds in children, and to examine potential for prevention. DESIGN: A two year six month retrospective analysis of admissions to a specialist burns unit. SETTING: The Burns Unit, St Lawrence Hospital, Chepstow serving children from south and west Wales. SUBJECTS: Sixty eight children attending the Burns Unit for treatment of bath related scald injuries. RESULTS: Bath scalds in children under 5 years of age was the cause of 14.7 per 100,000 children being admitted to the specialist burns unit in a year. The majority of the children were injured by falling in the bath but the tap was turned on by seven children themselves and by 10 siblings. Six children put hands in the hot water and two children were accidentally put into bath water that was too hot and were quickly withdrawn. Four children suffered probably non-accidental immersion scald injuries from hot water. They were characterised by a clear tide mark, a story that did not fit the injuries, associated injuries, and by symmetrical lesions. Accidental scalds were irregular geographical injuries and were asymmetrical. CONCLUSIONS: Bath scalds are a significant problem in children under 5 years. Their prevention should be part of an injury control programme on a local and national level. The best way to achieve this would be by reducing the temperature in domestic hot water tanks. The recognition of non-accidental bath scalds can be assisted by the pointers outlined and should be done in a multidisciplinary way with plastic surgeons, paediatricians, and social workers working together.

Accidents, Home↗
PubMed1993

IL-4 and interferon-gamma production in children with atopic disease.

In vitro studies have implicated reciprocal roles for IL-4 and interferon-gamma (IFN-gamma) in the regulation of IgE production. As elevated IgE is a major feature of atopic disease, an important question is whether an imbalance of IL-4 and IFN-gamma is present in vivo. The production of IL-4 and IFN-gamma in phytohaemagglutinin (PHA)-stimulated peripheral blood mononuclear cell cultures from atopic children was examined to determine if there is an increased production of IL-4 and/or a reduced production of IFN-gamma. Highly atopic children with IgE > 600 U/ml produced significantly more IL-4 and less IFN-gamma in vitro than age-matched non-atopic controls. Production of IL-4 and IFN-gamma in mildly atopic children was equivalent to controls. These findings indicate that highly atopic children have an imbalance of IL-4 and IFN-gamma production and that the degree of imbalance relates to severity of the atopic state. The ratio of in vitro IL-4: IFN-gamma production correlated positively with serum IgE, which suggests that the balance of these two cytokines is a factor in the regulation of IgE, in vivo. It remains to be determined whether this imbalance of IL-4 and IFN-gamma in the highly atopic children is the cause or result of the disease process.

Asthma↗
PubMed1992

Drowning and near drowning in children in the United Kingdom: lessons for prevention.

OBJECTIVES: To determine the pattern of drowning and near drowning of children in Britain and identify means of prevention. DESIGN: Study of drowned and nearly drowned children under 15 years old. SETTING: United Kingdom, 1988 and 1989. SUBJECTS: Children under 15 years either drowning or admitted to hospital after a submersion incident. MAIN OUTCOME MEASURES: Number of nearly drowned children, obtained from consultant paediatricians returning monthly notification cards through the British Paediatric Surveillance Unit. Number of drowned children notified by the Office of Population Censuses and Surveys and other national epidemiological offices; information from coroners. RESULTS: 306 children had confirmed submersion incidents: 149 died and 157 survived after near drowning. The annual incidence in England and Wales was 1.5/100,000, and mortality 0.7/100,000. Mortality was lowest in public pools 6% (2/32) and highest in rivers, canals, and lakes (78%, 56/73). Most of the children (263, 83%) were unsupervised at the time of the accident. 208 (68%) children were under 5 years old. CONCLUSIONS: Drowning and near drowning of children are problems in the British Isles. Appropriate supervision and safety barriers seem important for preventing such accidents. Improving information on dangers of drowning given to parents through the child surveillance programmes, encouraging fencing or draining of garden ponds and domestic swimming pools, and increasing supervision of swimming in lakes, rivers, and beaches should reduce the number of accidents.

Adolescent↗