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Biomedical subjects

M J Campbell

Publications and source records attributed to M J Campbell.

At least 19 recordsLinked to original sources

Management of feverish children at home.

OBJECTIVES: To compare the acceptability and effects on temperature of advice to unwrap children and give paracetamol or warm sponging treatments in the management of feverish illness at home. DESIGN: A randomised, open, parallel group study using factorial design comparison of unwrapping, warm sponging plus unwrapping, paracetamol plus unwrapping, and paracetamol and warm sponging plus unwrapping. SETTING: Homes of willing families with a feverish child recruited after consulting one of 21 participating general practitioners in Southampton. SUBJECTS: 52 children aged from 3 months to 5 years with axillary temperatures before treatment of > or = 37.8 degrees C and < 40 degrees C. MAIN OUTCOME MEASURES: Response to advice assessed over four hours; temperature assessed by continuous data logging from an axillary thermistor; acceptability of treatment to child and parent scored on Likert scales immediately after treatment and on return to health. RESULTS: Response to treatment advice varied; unwrapping alone had little effect on temperature. Paracetamol increased the time below 37.2 degrees C in four hours by 109 (95% confidence interval 74 to 145) minutes compared with unwrapping; warm sponging caused the fastest reduction in temperature. Parents discriminated between treatments, preferring paracetamol. CONCLUSION: Advice to give paracetamol is more effective than sponging or unwrapping in controlling temperature in children at home and is more acceptable to parents. Warm sponging has an additive effect and reduces fever more quickly than paracetamol.

Acetaminophen

Induction of immune responses in patients with B-cell lymphoma against the surface-immunoglobulin idiotype expressed by their tumors.

BACKGROUND: The idiotypic determinants of the surface immunoglobulin of a B-cell lymphoma can serve as a clonal tumor-specific marker, which may have implications for immunotherapy. We sought to determine whether idiotype-specific immune responses against this autologous antigen could be induced in patients with B-cell lymphoma. METHODS: Nine patients were selected who had minimal residual disease or a complete remission after chemotherapy. Each received a series of subcutaneous injections of the immunoglobulin derived from his or her tumor cells (immunoglobulin-idiotype protein), which had been conjugated to a protein carrier and mixed with an immunologic adjuvant. RESULTS: In seven of the nine patients the injections induced sustained idiotype-specific immunologic responses of the humoral type (two patients), the cell-mediated type (four patients), or both (one patient). The use of an adjuvant was essential for these immune responses. The induced antibodies bound specifically to autologous immunoglobulin idiotype, inhibited the binding of murine monoclonal antiidiotype antibodies, and bound autologous tumor cells. Cell-mediated responses were demonstrated by the specific proliferation of immune peripheral-blood mononuclear cells to the soluble immunoglobulin-idiotype protein in vitro. The tumors of both of the patients with measurable disease regressed completely. Toxicity associated with the vaccine was minimal and consisted only of mild reactions at the site of intramuscular injection. CONCLUSIONS: These results demonstrate that autologous immunoglobulin idiotype can be formulated into an immunogenic, tumor-specific antigen in humans with B-cell lymphoma, and they provide the background for large-scale trials of active specific immunotherapy of this disease.

Adjuvants, Immunologic

Tumor resistance induced by syngeneic bone marrow transplantation and enhanced by interleukin 2: a model for the graft versus leukemia reaction.

Lethally irradiated C3H/HeN mice reconstituted with normal syngeneic bone marrow survived significantly longer than unmanipulated control mice following challenge with a lethal dose of 38C13 lymphoma cells 2 to 3 weeks post-bone marrow transplantation (BMT). Although the magnitude of this effect was modest, it was highly reproducible. This resistance-producing effect of BMT could be enhanced by interleukin 2 administration and could be abrogated by anti-asialo-GM1 antiserum treatment of recipients. These findings are consistent with the hypothesis that cells with a natural killer phenotype are activated by BMT and can mediate tumor resistance. These studies provide a model to explore the cellular basis, independent of donor alloreactivity, of the graft antitumor effect of BMT observed in humans.

Animals

Randomised controlled trial of breast shells and Hoffman's exercises for inverted and non-protractile nipples.

OBJECTIVE: To determine the value of recommending breast shells or Hoffman's exercises, or both, to pregnant women with inverted or non-protractile nipples who intend to breast feed. DESIGN: Randomised controlled trial with a two treatment by two level factorial design. SETTING: Antenatal clinics in a district general hospital and the community. SUBJECTS: 96 nulliparous women recruited between 25 and 35 completed weeks in a singleton pregnancy with at least one inverted or non-protractile nipple. MAIN OUTCOME MEASURES: Anatomical change of nipples, judged blindly before first breast feeding, and success of breast feeding reported by postal questionnaire six weeks postnatally. RESULTS: Sustained improvement in nipple anatomy was more common in the untreated groups but the differences were not significant (52% (25/48) shells v 60% (29/48) no shells; difference -8% (95% confidence interval -28% to 11%) and 54% (26/48) exercises v 58% (28/48) no exercises; -4% (-24% to 16%)). 24 (50%) women not recommended shells and 14 (29%) recommended shells (21%; 40% to 2%) were breast feeding six weeks after delivery (p = 0.05), reflecting more women recommended shells both deciding to bottle feed before delivery and discontinuing breast feeding. The same number of women in exercise and no exercise groups were successfully breast feeding (0%; -20% to 20%). 13% of women approached about the trial (and planning to breast feed) did not attempt breast feeding. CONCLUSIONS: Recommending nipple preparation with breast shells may reduce the chances of successful breast feeding. While there is no clear evidence that the treatments offered are effective antenatal nipple examination should be abandoned.

Adolescent

Use of family specific leader region primers for PCR amplification of the human heavy chain variable region gene repertoire.

We have designed a set of six, non-degenerate oligonucleotide primers, corresponding to the 5' leader regions of each of the six human VH gene families. A general strategy for family specific polymerase chain reaction amplification is described using these primers and a conserved 3' primer corresponding to frame work 3, JH, or constant region. This strategy was used to isolate and sequence novel human germline VH genes belonging to the VH2 and VH4 families. Under certain conditions, chimeric VH sequences were created by a "jumping polymerase chain reaction", combining DNA segments from different germline genes, but this could be avoided by limiting the number of amplification cycles. PCR amplification with these family specific primers will facilitate studies of the repertoire of germline VH genes as well as studies on VH gene usage in normal and aberrant (B cell malignancies, autoimmune diseases, etc.) B cell populations.

Amino Acid Sequence

The interaction between immunoglobulin E and smoking in airflow obstruction in the elderly.

Airflow obstruction and serum immunoglobulin E (IgE) were assessed in 250 men and women 65 to 91 yr of age who had been selected from a larger general population sample according to reported respiratory symptoms. After allowance for age and sex, serum IgE and smoking interacted synergistically as risk factors for airflow obstruction such that on average an IgE > or = 81 IU/ml in current smokers was associated with a FEV1/FVC ratio 14.4 percentage points (95% CI, 8.8 to 19.9) less than in lifelong nonsmokers with an IgE < or = 10 IU/ml. This synergistic interaction was apparent in subjects who showed no evidence of airway lability (i.e., no hyperresponsiveness to inhaled methacholine or, if bronchial hyperresponsiveness could not be tested, no clear improvement in airflow obstruction after inhalation of salbutamol). The findings suggest that the role of IgE in the pathogenesis of airflow obstruction is not confined to asthmatics.

Age Factors

A longitudinal study of baseline FEV1 and bronchial responsiveness in patients with asthma.

The effect of initial airway calibre on the response to bronchial provocation is unclear. Theoretically, geometric relationships within the airways might influence the measurement of responsiveness, particularly since a given change in calibre will produce a disproportionately greater reduction in flow in airways which are already narrowed. We have examined the relationship between serial measurements of prechallenge forced expiratory volume in one second (FEV1) and responsiveness to methacholine (PD20) in 8 children and 12 adults with asthma. Measurements were made every 2-3 wks for 12-18 months and all patients kept a daily record of symptoms and twice daily measurements of peak expiratory flow (PEF). Spearman's rank correlation coefficient (rho) for the relationship PD20 versus pre-challenge FEV1 was derived for each patient and varied widely within the group (range -0.22 to 0.73, mean 0.31); the strength of this correlation was not related to a patient's mean FEV1 % predicted, but was related to the degree to which PD20 and pre-challenge FEV1 themselves reflected concurrent asthma severity (mean morning PEF and mean symptom scores for the three days around each test). This suggests that the observed relationship between pre-challenge FEV1 and PD20 may be due less to the influence of airway geometric factors, which might be expected to be present in all patients, but rather that pre-challenge FEV1 is reflecting the severity of the underlying disease. Larger studies will be needed to test this hypothesis further.

Adolescent

Transfer of specific immunity to B-cell lymphoma with syngeneic bone marrow in mice: a strategy for using autologous marrow as an anti-tumor therapy.

Persistence of the underlying malignancy remains the major obstacle limiting the success of high-dose chemoradiotherapy with autologous bone marrow transplantation (BMT) for non-Hodgkin's lymphomas. We used the 38C13 murine B-cell lymphoma model to explore the approach of transferring tumor antigen-specific immunity with syngeneic BM as a protective element. Mice serving as syngeneic marrow donors were twice immunized with tumor-derived surface Ig protein, the idiotype of which serves as a tumor-specific antigen, or with a control Ig of matched isotype. Naive lethally irradiated recipients reconstituted with marrow from immune donors showed serologic tumor idiotype-specific immunity, as well as protection against lethal tumor challenge. The immunoprotective effect of immune marrow was also shown in lethally irradiated recipients partially protected by specific immunization post-BMT. Combined donor and recipient immunization also replaced the requirement for the booster immunization of the donor. These results provide the rationale for active immunization with purified surface Ig from autologous tumor as an adjunct to autologous BMT in humans.

Animals

Ig VH gene expression among human follicular lymphomas.

Thirty-six randomly selected cases of low grade follicular lymphoma (FL) were analyzed for Ig heavy chain variable region (VH) gene expression. Assignment to one of the six human VH gene families (VH1 to VH6) was made with a polymerase chain reaction-based technique using family-specific leader primers. The frequency of VH family use in FL was found to be similar to that reported for normal peripheral blood lymphocytes and is therefore also roughly proportional to VH family size. To evaluate expression within an individual family, all of the lymphoma VH genes from the middle size VH4 family were sequenced and compared with previously published sequences. Of these eight lymphoma VH sequences, six were most closely related to just two of the 10 known functional VH4 germline genes. Nonrandom usage by FL of the JH3, JH4, and JH5 joining segments was also observed. Nucleotide sequences were also determined for 10 randomly selected lymphoma VH genes from the large VH3 family. With one possible exception, none of these lymphoma VH sequences appear to represent any of the VH3 genes that may be preferentially used in the fetal repertoire.

Base Sequence

Red blood cell magnesium and chronic fatigue syndrome.

The hypotheses that patients with chronic fatigue syndrome (CFS) have low red blood cell magnesium and that magnesium treatment would improve the wellbeing of such patients were tested in a case-control study and a randomised, double-blind, placebo-controlled trial, respectively. In the case-control study, 20 patients with CFS had lower red cell magnesium concentrations than did 20 healthy control subjects matched for age, sex, and social class (difference 0.1 mmol/l, 95% confidence interval [CI] 0.05 to 0.15). In the clinical trial, 32 patients with CFS were randomly allocated either to intramuscular magnesium sulphate every week for 6 weeks (15 patients) or to placebo (17). Patients treated with magnesium claimed to have improved energy levels, better emotional state, and less pain, as judged by changes in the Nottingham health profile. 12 of the 15 treated patients said that they had benefited from treatment, and in 7 patients energy score improved from the maximum to the minimum. By contrast, 3 of the 17 patients on placebo said that they felt better (difference 62%, 95% CI 35 to 90), and 1 patient had a better energy score. Red cell magnesium returned to normal in all patients on magnesium but in only 1 patient on placebo. The findings show that magnesium may have a role in CFS.

Adolescent

A subpopulation of primate corticocortical neurons is distinguished by somatodendritic distribution of neurofilament protein.

In recent immunohistochemical studies of human and monkey neocortex we observed that the somatodendritic distribution of neurofilament protein appears to be restricted to a subpopulation of pyramidal neurons. To further characterize this apparent specificity in cytoskeletal organization, combined retrograde tract tracing and immunohistochemical methods were used to examine the extent to which neurons from different cortical areas providing a projection to prefrontal cortex have a somatodendritic distribution of neurofilament proteins. These studies revealed that the proportion of neurons providing a projection from different cortical areas to prefrontal cortex varied from nearly 30% to 90%, and appeared to be related to the functional nature of the projection.

Amidines

Coping with extra Poisson variability in the analysis of factors influencing vaginal ring expulsions.

The vaginal ring is one method of contraception currently under investigation and development by the Human Reproduction Programme of WHO. One factor that reduces its acceptability is that some women experience involuntary expulsions of the ring. WHO have collected prospective data on 1005 women from 19 centres worldwide to investigate various aspects of ring use including factors that might affect expulsions. For each subject the data include number of expulsions, age, parity, ponderal index, number of days of ring use and health care centre. To model the factors influencing expulsion, the number of expulsions was first considered as a Poisson variate with mean directly proportional to the log of the duration of ring use. Such a model gave a poor description of the data and it appeared that the number of expulsions was considerably over-dispersed for an assumed Poisson variate. This paper examines a variety of strategies for coping with the resulting lack of fit of the model. It turns out that a truncated Poisson model gives a better description of the expulsion data and that health care centre and parity influence the rates.

Contraceptive Devices, Female

Follicular lymphoma: a model of lymphoid tumor progression in man.

Human follicular lymphoma can be viewed as a malignancy in evolution. Since this disease is composed of a clonal population of B lymphocytes all expressing a given immunoglobulin light chain and heavy chain, it seems possible that the initial transforming event, the t(14; 18) chromosomal translocation, occurs in a cell already committed to the expression of a particular VH and VL gene. A panel of antibodies has been assembled which define a set of idiotypes expressed repeatedly by B-cell lymphomas. Nonetheless, VH gene usage in follicular lymphoma tumors appears to reflect the normal B-cell repertoire. Growth of follicular lymphoma appears to be partially under normal regulatory control. The expanding malignant B-cell clone grows in follicles with particular apposition to follicular dendritic cells and heavy infiltration with CD4+ T cells. Interaction with T cells can induce the proliferation of follicular lymphoma cells. This tumor eventually evolves into a diffuse large-cell lymphoma which is highly aggressive and lethal. It is now clear that the malignant progression occurs from a single cell within the expanding follicular lymphoma clone. A panel of monoclonal antibodies to cell surface molecules has been generated that inhibit proliferation of diffuse lymphoma cell lines, and some of the target molecules have been partially characterized. Therapeutic application of anti-idiotype monoclonal antibodies has shown a high degree of tumor responsiveness, but ultimately escape of idiotype-negative variant cells occurs. These variants arise as a result of extensive somatic point mutation in the VH and VL genes of follicular lymphoma. Active immunization can result in an immune response by patients directed against the idiotype expressed on their own B-cell tumors.(ABSTRACT TRUNCATED AT 250 WORDS)

Cell Communication

Sudden infant deaths and cold weather: was the rise in infant mortality in 1986 in England and Wales due to the weather?

Using the daily number of deaths due to sudden infant death syndrome in England and Wales from 1979 to 1985, and the daily temperature recorded at the London Weather Centre, two models were constructed, one including a temperature term and one without it, and the models used to predict the mortality in 1986. It was found that the model using temperature had a slightly better predictive power and successfully accounted for the increased mortality in February 1986. Thus, we conclude that the excess mortality of February 1986 was associated with the unusually cold weather during that month.

Cold Climate

Assessment of the psychological impact of a breast screening programme.

In order to assess the psychological effect of mammographic screening, questionnaires (which included psychometric tests) were sent to 750 women at invitation and, 6 weeks after screening, to 420 women normal after the first mammograph, to 240 women normal after special assessment, and to 68 women normal after open biopsy. Increasing degree of the investigation was associated both with increasing frequency of breast self examination (10% were practising breast self-examination at least once a week before screening compared with 24% for women after special assessment and 35% of women who had had an open biopsy (p less than 0.001)), and with greater confidence that any malignancy in the breast would have been found. Psychometric scores showed no increase of general levels of anxiety or depression in the screened groups. For anxiety, percentages abnormal were 5, 4, 2 and 6 for the four groups, respectively, and for depression the percentages abnormal were 5, 4, 4 and 6, respectively; 10% of screened women were more anxious about having breast cancer as a result of the screening. At least 10% of women proceeding to open biopsy of benign lesions require professional counselling and support. Psychological ill effects were not detected by the psychometric test among women who did not proceed to this final investigation. Behavioural changes did suggest a raised awareness or fear of potential cancer among the screened population.

Aged