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Biomedical subjects

D I Phillips

Publications and source records attributed to D I Phillips.

At least 19 recordsLinked to original sources
PubMed1992

Association between postpartum thyroid dysfunction and thyroid antibodies and depression.

OBJECTIVE: To define the relation between mood and autoimmune thyroid dysfunction during the eight months after delivery. DESIGN: Double blind comparison of the psychiatric status of women positive and negative for thyroid antibodies. Clinical examination and blood sampling for free triiodothyronine and thyroxine, thyroid stimulating hormone, and thyroid antibody concentrations at four weekly intervals. Psychiatric assessment at six, eight, 12, 20, and 28 weeks post partum. SETTING: Outpatient department of district hospital. PATIENTS: 145 antibody positive women and 229 antibody negative women delivering between August 1987 and December 1989. MAIN OUTCOME MEASURES: Thyroid status. Number of cases of mental ill health by the general health questionnaire, research diagnostic criteria, Hamilton 17 item depression scale, hospital anxiety and depression scale, and Edinburgh postnatal depression scale. RESULTS: Six weeks after delivery the general health questionnaire showed 62 (43%) antibody positive women and 65 (28%) antibody negative women had mental ill health (chi 2 = 8.18, p less than 0.005). Follow up of 110 antibody positive and 132 antibody negative women showed significantly greater depression by research diagnostic criteria in antibody positive women (47%) than antibody negative women (32%) regardless of thyroid dysfunction. Antibody positive women showed higher mean scores for depression on the Hamilton (6.01 v 3.89, p = 0.0002), Edinburgh (7.45 v 5.92, p = 0.031), and hospital depression scales (4.95 v 3.79, p = 0.003). CONCLUSION: Depressive symptoms are associated with positive thyroid antibody status in the postpartum period.

Autoantibodies↗
PubMed1992

The sonographic appearances in postpartum thyroiditis.

During the postpartum period about 50% of women with circulating thyroid autoantibodies develop a transient autoimmune thyroiditis. To determine the sonographic appearances in postpartum thyroiditis (PPT), serial ultrasound (US) scans of the thyroid were performed in 135 postpartum women who were divided into three clinical groups: Group 1, 37 antibody positive subjects who developed PPT; Group 2, 28 antibody positive subjects in whom thyroid function remained normal; Group 3, 70 antibody negative controls. Thyroid hypoechogenicity was observed in 14/31 patients (45%) who were scanned between 4 and 8 weeks postpartum and who subsequently developed PPT (Group 1) compared with 4/24 patients (17%) in Group 2 (P less than 0.05) and 1/65 patients (1.5%) in Group 3 (P less than 0.001). In antibody positive patients, the positive predictive value of an abnormal scan during this period was 78%. Between 15 and 25 weeks postpartum thyroid hypoechogenicity was present in 32/37 patients (86%) in Group 1 compared with 11/28 patients (39%) in Group 2 (P less than 0.001) and 2/70 patients (3%) in Group 3 (P less than 0.001). Sonographic abnormality persisted beyond 32 weeks postpartum in 36/41 antibody positive patients (87%) who had exhibited thyroid hypoechogenicity earlier during the study and who had late scans. The characteristic US appearance in PPT is thyroid hypoechogenicity. The role of sonography in the prediction, diagnosis and follow up of patients with PPT is discussed.

Autoantibodies↗
PubMed1992

Iodine metabolism in postpartum thyroiditis.

To investigate the etiologic role of iodine intake in postpartum thyroiditis (PPT), we have measured postpartum urinary iodine excretion serially in a large prospective study of PPT. A total of 1996 women were screened for thyroid microsomal antibody during the second trimester of pregnancy. One hundred fifty-two of the 235 antibody-positive women and an equal number of age-matched antibody-negative controls were followed postpartum with measurements of urinary iodine and thyroid function at monthly intervals for 12 months. Iodine excretion in the immediate postpartum period did not differ between the 73 women who developed PPT and the antibody-negative controls. In women with PPT with hyperthyroidism, hypothyroidism, or hyperthyroidism followed by hypothyroidism, increased urinary iodine excretion was observed between 8 and 16 weeks postpartum, which preceded the hormonal disturbances among the women with hypothyroidism. The height of the rise in urinary iodine excretion during the first 20 weeks postpartum correlated with the serum free thyroxine levels (r = 0.61, p less than 0.001). Iodine intake is unlikely to affect the prevalence of PPT. However, these data show that the hyperthyroid phase of PPT is associated with a significant release of intrathyroidal iodine due to thyroid destruction and that the same process also occurs to a lesser extent before the hormonal disturbances associated with hypothyroid PPT.

Autoantibodies↗
PubMed1992

Surrogate thyroglobulin receptors and T cell proliferation in Hashimoto's thyroiditis.

Immunoglobulin molecules on the surface of a B lymphocyte are the endogenous "receptors" to which specific antigens bind. Studies in mice have shown that a monoclonal antibody, conjugated with palmitate to provide a lipid tail, can be inserted into the cell membrane to provide a "surrogate" antigen receptor. We have investigated whether a palmitate conjugate of a human monoclonal antibody specific for thyroglobulin (TG) could function as a surrogate TG receptor on blood mononuclear cells separated into fractions enriched for T cells or depleted of T cells (non-T cells). Using flow cytometry, we detected surrogate TG receptors on non-T (but not on T) cells from 11 of 11 individuals studied (5 Hashimoto patients and 6 control donors). In contrast, endogenous TG receptors could only be detected on non-T cells from 1 of 3 Hashimoto patients and from 0 of 4 control donors. Because of the efficient binding of TG by surrogate receptors on non-T cells, we assessed the ability of such cells to present TG to T cells. Proliferation in response to TG was observed in T cells from only 1 of 5 Hashimoto patients. This low frequency of response was no different from that previously detected using cultures of T cells and autologous dendritic cells. Therefore, the successful generation of surrogate receptors on non-T cells is not associated with more efficient TG presentation of T cells. Furthermore, the significance of the present study is that the T cells, not the antigen-presenting cells, are likely to be the limiting element in the T cell proliferative response to TG and other thyroid autoantigens.

Antibodies, Monoclonal↗
PubMed1991

Severe combined immunodeficient (SCID) mice: a model for investigating human thyroid autoantibody synthesis.

We have studied the ability of lymphocytes from the blood, thyroid and lymph nodes of patients with autoimmune thyroid disease (AITD) to produce autoantibodies to thyroglobulin (Tg) and/or thyroid peroxidase (TPO) in SCID mice. Human IgG class Tg and/or TPO antibodies were detectable in plasma from SCID mice 7 days after transfer of 15-25 x 10(6) cells/mouse and the highest levels were recorded 2-3 weeks later. In contrast, Tg and/or TPO antibodies were undetectable in recipients of lymphocytes from thyroid antibody negative controls. AITD thyroid lymphocytes produced the most antibody in recipient mice and lower levels were observed in recipients of AITD blood and lymph node lymphocytes. The amounts of Tg and/or TPO antibody detected were in accordance with the ability of thyroid and lymph node lymphocytes to secrete these autoantibodies spontaneously in culture (indicating the presence of cells activated in the patient) and with the capacity of blood lymphocytes (probably B memory cells) to secrete Tg and/or TPO antibodies in culture in response to pokeweed mitogen. Tg antibodies in plasma from SCID recipients of thyroid lymphocytes were of subclasses IgG1, IgG2 and IgG4 and the proportions closely resembled those of the donor's serum Tg antibodies. Blood lymphocytes transferred to SCID recipients were also able to produce Tg antibodies of subclasses 1, 2 and 4 but the subclass distribution varied between mice and the reason for this is not clear at present. Since SCID mice provide an environment in which B lymphocytes from patients with AITD can be activated without mitogen to secrete thyroid antibodies, this model will provide a powerful system for elucidating the mechanisms regulating the secretion of human antibodies to Tg and TPO.

Animals↗
PubMed1991

Effect of low dose iodide supplementation on thyroid function in potentially susceptible subjects: are dietary iodide levels in Britain acceptable?

OBJECTIVE The aim of the study was to evaluate the risk of exposure to an increase in dietary iodide intake amongst potentially susceptible population groups in Britain. DESIGN A randomized controlled trial was performed in healthy women and in women with underlying thyroid abnormalities due to subclinical Hashimoto's thyroiditis (diagnosed on the basis of antithyroid antibodies) or previous iodide deficiency of supplementation with 500 micrograms/day iodide (giving a total intake of approximately 750 micrograms/day) for 28 days versus placebo. PATIENTS Two hundred and twenty-five women aged 25-54, randomly selected from a general practice in Cardiff, were screened for thyroid microsomal antibody. Antibody positive women (n = 20), and antibody negative controls (n = 30) were recruited into the trial comparing iodide and placebo. In addition, groups of patients aged 60-75 randomly selected from the Cardiff practice (n = 29), an iodide sufficient area, and a practice in Dowlais (n = 35), a previously iodide deficient area, were also enrolled into the trial. MEASUREMENTS Changes in free thyroxine and thyrotrophin levels were measured after 14 and 28 days of iodide supplementation. RESULTS All the iodide supplemented groups responded in the same way with a small fall in free thyroxine and rise in thyrotrophin levels (combined fall in free thyroxine 14 days after the start of supplementation -1.22 (95% confidence interval -0.59 to -1.84) pmol/l and at 28 days -0.86 (-0.30 to -1.43) pmol/l and rise in thyrotrophin at 14 days 0.55 (0.19 to 0.92) mU/l and at 28 days 0.59 (0.12 to 1.07) mU/l). In two of the iodide supplemented subjects thyrotrophin levels rose above the laboratory reference range and in a further three subjects initially elevated thyrotrophin values increased further. In contrast, no changes in thyroid function were observed in the placebo treated controls and none developed biochemical hypothyroidism. CONCLUSIONS Dietary iodide intakes of 750 micrograms/day or more may adversely affect thyroid function, especially in individuals with borderline hypothyroidism.

Adult↗
PubMed1991

Smoking, humoral immunity, and ulcerative colitis.

Since ulcerative colitis predominantly affects non-smokers and ex-smokers we have examined the possibility that smoking modifies the humoral immune response to an antigenic challenge from the gut lumen. Gut lavage was used in healthy subjects and patients with ulcerative colitis, including both smokers and non-smokers. Antibodies in the intestinal fluid to Escherichia coli (five pooled serotypes), Candida albicans, gliadin, ovalbumin, and beta lactoglobulin were measured by ELISA to determine specific antibody concentrations of IgG, IgA, and IgM classes. Total IgG, IgA, and IgM were also measured in intestinal secretions and serum. In addition, circulating antibody concentrations of IgG, IgA, and IgM to three gut commensals - E coli (five pooled serotypes) C albicans, and Poroteus mirabilis were measured. There was a significant reduction in the IgA concentration in intestinal fluid of smokers with ulcerative colitis compared with healthy non-smoking controls. No other significant differences were found between the groups. Overall, these data are not consistent with the idea that smoking suppresses immune responses in the gut and suggest that the effect of smoking in colitis is mediated by another mechanism.

Adult↗
PubMed1991

Papilloedema and cranial nerve palsies complicating apparent benign aseptic meningitis.

Three patients who presented with apparently uncomplicated aseptic meningitis subsequently developed papilloedema and sixth cranial nerve palsies between 11 and 16 days after the onset of the illness. All three patients recovered completely without treatment. Raised intracranial pressure is a poorly recognized complication of aseptic meningitis that may represent a post-infective or 'allergic' response to an enteroviral infection. While clinicians should be aware of this possible complication of aseptic meningitis, differentiation from tuberculous meningitis may be difficult necessitating empirical treatment with anti-TB drugs.

Abducens Nerve↗
PubMed1990

Thyroid autoantigens and human T cell responses.

We investigated the ability of T cells from patients with Hashimoto's thyroiditis and with Graves' disease as well as control donors to proliferate in response to thyroid peroxidase (TPO) and thyroglobulin using (i) lymphoid cells from different lymphoid organs; (ii) unfractionated or CD8- depleted lymphoid suspensions or T cells + autologous low density cells (LDC); (iii) 200-microliters well cultures and 20-microliters hanging-drop microcultures; and (iv) intact TPO and thyroglobulin, denatured thyroglobulin and 12 synthetic peptides predicted on the basis of the amino acid sequence of TPO to be T cell epitopes. In 200-microliters well cultures, proliferative responses (assessed in terms of 3H-thymidine uptake) to intact TPO or thyroglobulin, digested thyroglobulin or synthetic TPO peptides were not significantly different in unfractionated or CD8-depleted lymphoid suspensions from blood, thyroid or lymph nodes of TPO/thyroglobulin autoantibody-positive patients, autoantibody-negative patients or control donors. In contrast, blood T cells from some high titre patients with Hashimoto's thyroiditis (but not from healthy individuals) proliferated in response to intact thyroglobulin or TPO presented by autologous LDC in hanging-drop microcultures. Heat denatured thyroglobulin (with which thyroglobulin autoantibodies do not interact) did not stimulate proliferation and this observation, together with the ability of T cells from some patients to respond to intact thyroglobulin in the absence of LDC, indicated that thyroglobulin-specific B cells may be involved in antigen presentation. As we were unable to demonstrate proliferation by blood T cells + LDC from all thyroglobulin antibody-positive patients with Hashimoto's thyroiditis, our studies suggest that the presence of sufficient precursor T cells, as well as the number and type of antigen-presenting cells, are critical for T cell proliferative responses to human TPO and thyroglobulin.

Antigen-Presenting Cells↗
PubMed1990

The influence of pregnancy and reproductive span on the occurrence of autoimmune thyroiditis.

A study comparing the reproductive histories of 89 women affected by Hashimoto's thyroiditis (HT) with 89 matched controls has been carried out to determine whether endogenous hormones contribute to the development of the disease. There was no evidence of an association between HT and parity and no trend to an increasing disease risk with increasing parity. However, patients with HT had a longer reproductive span. There was a significant trend to a lower risk with later age at menarche (relative risk (RR) of menarche at 13-14 years compared with less than or equal to 12 years = 0.71, and greater than or equal to 15 years compared with less than or equal to 12 years = 0.45), and an increased risk with a later menopause (greater than or equal to 51 years compared with less than or equal to 50 years, RR = 3.00, P less than 0.025). An additional finding was an increased hysterectomy rate among the cases. These observations may be explained if the hyperoestrogenic state associated with a longer reproductive span acted to modulate the immune process in autoimmune thyroid disease.

Adolescent↗
PubMed1990

A long-term follow-up of postpartum thyroiditis.

To investigate the long-term outcome of postpartum thyroiditis (PPT), 43 patients with PPT and 171 control women were evaluated 3.5 (range 2-4) years postpartum. Ten (23%) PPT patients were hypothyroid compared to none of the controls (P less than 0.001). Factors associated with the development of hypothyroidism were high antimicrosomal antibody titre measured at 16 weeks gestation (P less than 0.01), severity of hypothyroid phase of PPT, multiparity, and a previous history of spontaneous abortion. The presence of microsomal antibody but no PPT in one pregnancy did not prevent the occurrence of PPT in the next pregnancy in two patients and a further five patients had PPT in two successive pregnancies. There was no association between HLA haplotype, family history of thyroid disease, smoking or frequency of oral contraception, and the development of long-term hypothyroidism after PPT. It is concluded that permanent hypothyroidism is an important sequel to PPT and patients with PPT should be followed up appropriately.

Adult↗
PubMed1990

Geographical distribution of subclinical autoimmune thyroid disease in Britain: a study using highly sensitive direct assays for autoantibodies to thyroglobulin and thyroid peroxidase.

In order to determine whether the geographical distribution of autoimmune thyroid disease in Britain is influenced by the pattern of iodine intake, the prevalence of subclinical disease (detectable antithyroid antibodies in biochemically euthyroid individuals) has been measured in female blood donors from seven towns in England and Wales previously characterised in terms of past and present iodine intake. Thyroglobulin antibody and thyroid peroxidase antibody were measured by highly sensitive assays which are based on the direct interaction between antibody and radiolabelled antigen. Excluding cases of overt thyroid disease (biochemically hypo- or hyperthyroid with thyroid antibodies), the overall prevalences of the antibodies in sera from the 698 female blood donors were 17.8% for thyroglobulin antibody and 17.8% for thyroid peroxidase antibody. Both antibodies were found in 12.3% of the female blood donors. In contrast, the prevalences of thyroglobulin antibody and thyroid peroxidase antibody were 41 and 43%, respectively, in the 117 female relatives of 18 probands with autoimmune thyroid disease, but the highest prevalences were observed in groups of women patients with Graves' disease (N = 39) or Hashimoto's disease (N = 39) (51, and 97% for thyroglobulin antibody, respectively, and 72 and 97% for thyroid peroxidase antibody, respectively). Antibody prevalence increased with age in the female blood donors rising from 10.6% at age 18-24 to 30.3% at age 55-64 for thyroglobulin antibody and from 14.9% at age 18-24 to 24.2% at age 55-64 for thyroid peroxidase antibody. Geographical differences in the prevalences of both antibodies were not significant and did not correlate with either the previous goitre prevalence or with current differences in iodine intake.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1990

Potential role of PHA in producing human monoclonal thyroid autoantibodies of different subclasses.

A human monoclonal autoantibody to thyroglobulin (Tg) of subclass IgG2 was developed by fusing a mouse myeloma with Tg antibody secreting Epstein-Barr virus (EBV)-infected B lymphocytes from a Hashimoto patient. Subsequent studies showed that EBV-infected B lymphocytes from this patient synthesized IgG2 Tg antibody while unfractionated blood lymphocytes cultured with pokeweed mitogen secreted IgG1, IgG2, and IgG4 Tg antibodies in amounts proportional to those present in the patient's serum. To investigate this discrepancy further, we cultured EBV-infected lymphocytes from blood, lymph nodes, and thyroid tissue in medium alone and with increasing concentrations of PHA. In individuals with thyroid autoantibodies predominantly of subclass IgG1, PHA enhanced the levels of total Tg antibody synthesis without affecting the IgG subclass distribution. However, in patients with serum autoantibodies of subclasses IgG1, 2, and 4, the increased levels of total Tg antibody synthesis were associated with increased amounts of thyroid autoantibodies of all of these subclasses; in some instances IgG1 and IgG4 autoantibodies were only synthesized in cultures containing PHA. These observations suggest that addition of the T-cell mitogen PHA to cultures of EBV-infected lymphocytes may ensure activation of B-cell precursors committed to synthesizing the IgG subclasses characteristic of serum antibody in the lymphocyte donor. Since Tg antibodies of subclasses IgG2 and IgG4 recognize different epitopes on Tg, the ability to produce human monoclonal antibodies of different IgG subclasses may simultaneously ensure the development of antibodies to different epitopes on the same antigen.

Animals↗
PubMed1989

Iodine supplementation with oral or intramuscular iodized oil. A two-year follow-up of a comparative trial.

A controlled trial of iodine supplementation comparing oral with intramuscular iodized oil has been carried out in an iodine deficient area of Zaire. Two years after the administration of 2 ml of oral iodized oil to the population of four villages the overall goitre prevalence had fallen from 64 to 54%. In a further two villages given 2 ml of intramuscular oil the prevalence fell from 65 to 50%. The effectiveness of supplementation was also assessed by measuring changes in thyroid function in women of reproductive age. Among women in the villages given oral iodized oil, the geometric mean thyroxine concentration, measured in dried bloodspots, rose from 27.2 to 52.6 nmol/L at the two-year follow-up. This was similar to the response of the intramuscularly treated villages in which thyroxine levels rose from 32.1 to 65.4 nmol/L. There was no change in goitre prevalence or thyroid function in two control villages. Oral iodized oil is a cheaper and simpler alternative to the injected form providing effective iodine prophylaxis for up to two years after a single dose.

Administration, Oral↗
PubMed1989

The influence of T cell depletion on recovery of T cell proliferation to herpesviruses and Candida after allogeneic bone marrow transplantation.

To test the influence of T cell depletion of the marrow in allogeneic bone marrow transplantation on functional T cell recovery, in vitro lymphocyte proliferation tests (LPTs) to microbial antigens were regularly performed in 23 recipients of normal BM and in 25 patients receiving BM with a fixed low number of T cells (1 x 10(5) T cells/kg body weight; recipients of T-depleted BM). The long-term recovery of positive LPT to at least 1 of the 4 tested microbial antigens--Candida, herpes simplex virus (HSV), varicella-zoster virus (VZV), and cytomegalovirus--was nearly similar in both groups: 16/23 versus 18/25. Recovery of LPT to Candida and HSV in the first 3 months appeared to be greatly influenced by prophylactic measures; only 2/23 recipients of normal BM, receiving amphotericin B, showed a positive LPT to Candida versus 13/25 recipients of T-depleted BM (P less than 0.01). In contrast, only 1/23 seropositive recipients of T-depleted BM, receiving acyclovir, showed a positive LPT to HSV versus 9/22 recipients of normal BM (P less than 0.05). A positive LPT to CMV in the first 3 months was found in 9/9 seropositive recipients of normal BM, versus in 5/11 seropositive recipients of T-depleted BM (P less than 0.05). Five of the 6 patients with a negative LPT died of CMV-interstitial pneumonia versus 1/14 with positive LPT (P less than 0.01). We conclude that in CMV-seropositive recipients of allogeneic BM, T cell depletion of the graft affects the early recovery of T cell proliferation to CMV, which is associated with a higher risk of fatal CMV-interstitial pneumonia.

Antigens, Fungal↗
PubMed1989

The effect of theophylline on thyrotoxic tremor.

1. The effect of intravenous aminophylline on theophylline-induced tremor were studied in six hyperthyroid patients before and after treatment to euthyroidism. 2. Baseline tremor power was significantly greater in the hyperthyroid compared with the euthyroid state (P less than 0.05). 3. Aminophylline produced a significantly greater increase in tremor power in the hyperthyroid compared with euthyroid state. 4. There was a significant increase in plasma theophylline clearance and reduction in t1/2 elimination when patients were hyperthyroid but volume of distribution did not change. 5. Intravenous aminophylline potentiates the tremor produced in hyperthyroidism despite an increase in plasma theophylline clearance. A pharmacodynamic mechanism is therefore likely.

Aged↗