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D Topliss

Publications and source records attributed to D Topliss.

9 recordsLinked to original sources
PubMed1998

The prognostic value of thyrotropin receptor antibody measurement in the early stages of treatment of Graves' disease with antithyroid drugs.

In most trials, at least 50% of patients with Graves' disease treated with antithyroid drugs (ATD) relapse after achieving euthyroidism. At present, there are no definitive prognostic parameters available early in treatment to indicate those likely to achieve long-term remission. Because thyrotropin receptor antibodies (TRAb) are specific for Graves' disease, the possibility that their rate of change early in treatment (0 to 6 months) might be such an indicator was explored. TRAb were measured both as thyrotropin binding inhibitory immunoglobulins (TBII) and as thyroid-stimulating antibodies (TSAb) in 85 patients with untreated Graves' disease at 6-month intervals throughout their ATD treatment. The patients in the study were treated for a minimum period of 12 months and were categorized retrospectively into two groups depending on whether or not they remained in remission after ATD treatment. Remission was deemed as reached in patients who remained euthyroid for a minimum period of 15 months after cessation of ATD. The mean initial TBII and TSAb values in the nonremission group were significantly higher than in the remission group (p < 0.001 for both parameters). The rates of fall in mean TBII levels were similar for each group in the first 6 months of treatment, but while they continued to fall in the remission group over the next 6 to 12 months, mean values for the nonremission group plateaued and failed to fall to control levels within that period. These results indicate that changes in TRAb levels, measured either as TBII or TSAb, occur more rapidly in the second 6 months of treatment in patients who ultimately achieve remission than those who do not. If TBII fall to control levels by 12 months, the patient has at least a 70% chance of ultimately achieving remission with ATD treatment alone.

Adult↗
PubMed1998

The Australian Multicenter Trial of Growth Hormone (GH) Treatment in GH-Deficient Adults.

GH treatment in adults with GH deficiency has numerous beneficial effects, but most studies have been small. We report the results of an Australian multicenter, randomized, double-blind, placebo-controlled trial of the effects of recombinant human GH treatment in adults with GH deficiency. GH deficiency was defined as a peak serum GH of < 5 mU/liter in response to insulin-induced hypoglycemia. Patients were randomly assigned to receive either GH (0.125 U/kg per week for 1 month and 0.25 U/kg per week for 5 months) or placebo. After 6 months, all patients received GH. The primary end points were biochemical responses, body composition, quality of life, and safety. One hundred sixty-six patients (72 females and 91 males) with a mean age of 40 +/- 1 yr (+/- SEM; range 17-67 yr) were recruited. Serum insulin-like growth factor-I (IGF-I) increased from a standard deviation score of -2.64 +/- 0.27 (range -8.8 +3.82; n = 78) to +1.08 +/- 2.87 (range -7.21 to +6.42) at 6 months in the GH/GH group; 38% of the whole group were above the age-specific reference range following treatment [17.6% and 68.9% with subnormal (< 2 SD) or normal (+/- 2 SD) pretreatment levels, respectively]. Fasting total cholesterol (P = 0.042) and low-density lipoprotein cholesterol (P = 0.006) decreased over the first 6 months. Fat-free mass increased in the first 6 months whether measured by bioelectrical impedance (P < 0.001) or dual energy x-ray absorptiometry (DEXA; P < 0.001). Total-body water increased in the first 6 months whether measured by bioelectrical impedance (P < 0.001) or deuterium dilution (P = 0.002). Fat mass measured by DEXA (P < 0.001), skinfold thicknesses (P < 0.001), and waist/hip ratio (P = 0.001) decreased in the first 6 months. Most changes in body composition were complete by 3 months of treatment and maintained to 12 months. Whole-body bone mineral density (BMD) (by DEXA) was unaffected by GH treatment. Self-reported quality of life was considered good before treatment, and beneficial treatment effects were observed for energy, pain, and emotional reaction as assessed by the Nottingham Health Profile. In the initial 6 months, adverse effects were reported by 84% of patients in the GH and 75% in the placebo group, with more symptoms relating to fluid retention in the GH group (48% vs. 30%; P = 0.016). Such symptoms were mild and resolved in 70% of patients despite continued treatment. Resting blood pressure did not change over the initial 6 months. In summary, GH treatment in adults with GH deficiency resulted in 1) prominent increases in serum IGF-I at the doses employed, in some cases to supraphysiological levels; 2) modest decreases in total- and low-density lipoprotein cholesterol, together with substantial reductions in total-body and truncal fat mass consistent with an improved cardiovascular risk profile; 3) substantial increases in lean tissue mass; and 4) modest improvements in perceived quality of life. The excessive IGF-I response and side-effect profile suggests that lower doses of GH may be a required for prolonged GH treatment in adults with severe GH deficiency.

Adult↗
PubMed1983

Evidence for cell-mediated immunity and specific suppressor T lymphocyte dysfunction in Graves' disease and diabetes mellitus.

Migration inhibition of purified peripheral T lymphocytes in response to pancreatic islet cell antigen or thyroid antigen was used to study cell-mediated immune mechanisms in patients with diabetes mellitus (IDDM) and Graves' disease (GD). In response to islet cell antigen, T lymphocytes of subjects with IDDM for less than 3 yr exhibited migration inhibition, whereas those of normal subjects, noninsulin dependent diabetics, and subjects with IDDM for longer than 3 yr did not. Admixture of T lymphocytes from normal subjects with T lymphocytes from patients with IDDM for less than 3 yr substantially ameliorated the migration inhibition of the IDDM subjects to islet cell antigen. Migration of T lymphocytes from GD subjects was markedly inhibited by thyroid antigen and marginally inhibited by islet cell antigen. Admixture of GD T lymphocytes significantly ameliorated the migration inhibition of IDDM T lymphocytes to islet cell antigen, despite sensitization to thyroid antigen of the GD T lymphocytes. We conclude: 1) sensitization to islet cell antigen in IDDM of recent onset is confirmed; 2) the ability of normal and GD T lymphocytes to ameliorate the migration inhibition of IDDM T lymphocytes strongly suggests correction of deficient suppressor T lymphocyte function; 3) the ability of GD T lymphocytes to ameliorate migration inhibition of IDDM T lymphocytes to islet cell antigen is evidence for an antigen-specific rather than a generalized suppressor T lymphocyte defect in GD; and 4) similarly, the normalization of migration index of GD T lymphocytes in response to thyroid antigen by those IDDM T lymphocytes not sensitized to thyroid antigen is again evidence for an antigen-specific and not a generalized suppressor T lymphocyte defect in IDDM.

Antigens↗
PubMed1981

T-lymphocyte sensitization in Graves' and Hashimoto's diseases confirmed by an indirect migration inhibition factor test.

T-Lymphocyte sensitization in Graves' disease (GD) and Hashimoto's thyroiditis (HT) was studied by an indirect migration inhibition factor test using normal T-lymphocytes as second stage indicator cells. In the first stage, mononuclear cells or T-lymphocytes, fractionated by the standard Ficoll-Hypaque procedure from the blood of patients with untreated GD and HT, were cultured in Eagle's medium containing thyroid antigen, and their cell-free supernatants were saved. Normal T-lymphocytes as second stage indicator cells were packed in capillary tubes and placed in planchettes with the above supernatants to complete the indirect migration inhibition factor test. Inhibition of the migration of indicator T-lymphocytes was demonstrated when either GD or HT culture supernatants were employed. Moreover, there was a good correlation between the indirect using the culture supernatants and the direct migration inhibition factor test using mononuclear cells or T-lymphocytes. On the other hand, in both direct and indirect migration inhibition factor tests using mononuclear cells and mononuclear cell culture supernatants, respectively, in the presence of human liver antigen as a nonspecific antigen, there was no significant difference between controls and patients. From these results, we can conclude that GD and HT T-lymphocytes are sensitized to thyroid antigen and produce the lymphokine, migration inhibition factor, into the supernatant when exposed to this antigen.

Adult↗
PubMed1981

Suppressor T lymphocyte dysfunction in Graves' disease: role of the H-2 histamine receptor-bearing suppressor T lymphocytes.

The allo-suppressor effect of normal T lymphocytes on the production of migration inhibition factor by sensitized T lymphocytes of Graves' disease in response to human thyroid antigen has been studied further by a modified migration inhibition factor test employing purified T lymphocyte preparations. The production of migration inhibition factor was consistently abolished when normal T lymphocytes were mixed with the Graves' disease lymphocytes in various ratios (1:9, 2:8, and 5:5). However, pretreatment of the normal T lymphocytes with cimetidine (an H-2 histamine receptor antagonist) led to a demonstrable loss in their allo-suppressor properties, whereas pretreatment with chlorpheniramine (an H-1 histamine receptor antagonist) had no such effect. These studies indicate that a subset of normal T lymphocytes bearing H-2 histamine receptors suppresses the production or release of migration inhibition factor by sensitized T lymphocytes, and further suggest the possibility that there may be an abnormality in the H-2 receptors on Graves' disease suppressor T lymphocytes. It is conceivable that this defect is fundamental in the pathogenesis of Graves' disease.

Adult↗