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Biomedical subjects

P Athanassiou

Publications and source records attributed to P Athanassiou.

13 recordsLinked to original sources

Mixed medullary-follicular thyroid carcinoma. Report of a case and review of the literature.

OBJECTIVE: The aim was to describe the case of a female patient with a mixed medullary-follicular thyroid carcinoma. METHODS: The patient underwent thyroidectomy for the treatment of multinodular goiter. A tumor was found which exhibited the features of a mixed medullary-follicular thyroid carcinoma. Immunohistochemistry was performed. RESULTS: Immunohistochemistry was positive in the area of the carcinoma for calcitonin and thyroglobulin. She developed extensive metastatic deposits in the bones of the pelvis and in the calvarium causing hyperthyroidism. CONCLUSION: A patient with a mixed medullary-follicular thyroid carcinoma is described, who had elevated levels of both calcitonin and thyroglobulin and developed metastatic deposits, which could produce thyroid hormones.

Adenocarcinoma, Follicular↗

Overrepresentation of the Fcgamma receptor type IIA R131/R131 genotype in caucasoid systemic lupus erythematosus patients with autoantibodies to C1q and glomerulonephritis.

OBJECTIVE: To test the hypothesis that there is an association between the Fcgamma receptor type IIA (FcgammaRIIA)-H/R131 polymorphism and autoantibodies to the collagenous region (CLR) of C1q in patients with systemic lupus erythematosus (SLE). METHODS: One hundred ninety-five Caucasoid lupus patients were studied. Anti-C1q(CLR) antibodies in serum were measured by enzyme-linked immunosorbent assay (ELISA) and FcgammaRIIA genotype analysis was performed by polymerase chain reaction. Immunoglobulin subclass of the autoantibodies was measured by ELISA. RESULTS: Fifty-six patients were anti-C1q antibody positive, and Ig subclass analysis indicated a predominance of IgG2 anti-C1q antibodies. Analysis of the SLE population as a whole revealed no significant difference in the allele frequencies of R131 and H131 compared with controls. There was, however, a significantly increased frequency of the R131 allele both in the anti-C1q-positive subgroup of patients (chi2 = 7.66, P<0.01) and in the 71 patients with nephritis (chi2 = 7.76, P< 0.01), compared with controls. CONCLUSION: FcgammaRIIA-R131 constitutes a heritable susceptibility factor for the development of SLE with manifestations in the kidney in Caucasoid patients. The close associations demonstrated between this FcgammaRII variant, antibodies to C1q(CLR), and glomerulonephritis may be due to a failure of clearance of the potentially pathogenic IgG2 autoantibody.

Alleles↗

Neurohypophysial hormone and melatonin secretion over the natural and suppressed menstrual cycle in premenopausal women.

OBJECTIVE: Vasopressin, oxytocin and melatonin have been reported to be influenced by ovarian steroids. The neurohypophysial hormones have also been shown to display a diurnal pattern of secretion in men. We therefore studied the diurnal pattern of neurohypophysial hormone and melatonin secretion in premenopausal women and in women on oral contraceptives. DESIGN: Healthy normally cycling premenopausal women were studied over 24 hours during the midfollicular and midluteal phases of the menstrual cycle. Healthy premenopausal women on oral contraceptives were studied over 24 hours at similar times. SUBJECTS: Eight healthy normally cycling women and 7 healthy premenopausal women on oral contraceptives. MEASUREMENTS: Plasma vasopressin, oxytocin and melatonin were measured by radioimmunoassay. RESULTS: Vasopressin concentrations and its nocturnal peak were highest in the follicular phase of the natural menstrual cycle and attenuated in the women on oral contraceptives. Oxytocin concentrations did not vary between the two phases of the menstrual cycle, but increased on oestrogen administration. Overall melatonin secretion was augmented in the women on oral contraceptives. CONCLUSIONS: Vasopressin release and its nocturnal peak were greatest in the follicular phase of the menstrual cycle, while melatonin secretion was augmented in the women on oral contraception.

Adult↗

Thyroid function in postmenopausal women with breast cancer on tamoxifen.

In 42 postmenopausal women with breast cancer, aged 48-85 years (mean age 62.4 years) serum thyroid hormone concentrations were measured before and after 6 months of tamoxifen therapy (20 mg daily). In particular triiodothyronine (T3), thyroxine (T4), free triiodothyronine (FT3), free thyroxine (FT4), thyroxine-binding globulin (TBG) and thyroid-stimulating hormone (TSH) concentrations before and 30 minutes after thyrotrophin-releasing hormone (TRH) administration (200 microg i.v.) were measured before and 6 months after tamoxifen therapy. T3 and T4 concentrations increased significantly (p<0.001 and p<0.05, respectively) whereas FT3 and FT4 remained unchanged (p>0.05), TBG increased significantly (p<0.001) and basal TSH concentrations as well as TSH response to TRH injection increased significantly (p<0.05) after tamoxifen therapy. It is concluded that tamoxifen administration changes thyroid hormone concentrations. However free thyroid hormone levels remain unchanged and the patients remain euthyroid after long-term tamoxifen therapy.

Aged↗

Sex hormones in postmenopausal women with breast cancer on tamoxifen.

In 42 postmenopausal women with breast cancer aged 48-85 (mean age 62.4) years, the blood sex hormone levels were measured before and after 6 months of tamoxifen administration (20 mg daily). Follicle-stimulating hormone and luteinizing hormone levels decreased after tamoxifen administration (p < 0.001), but remained in the postmenopausal range, oestradiol levels increased (p < 0.05), sex hormone binding globulin levels increased (p < 0.001), testosterone levels remained stable (p > 0.1), free testosterone levels decreased (p < 0.001), delta4-androstenedione, 17-hydroxyprogesterone, and dehydroepiandrosterone sulfate levels remained unchanged (p > 0.1), and basal prolactin levels and their response to thyrotrophin-releasing hormone injection decreased significantly (p < 0.001) after tamoxifen therapy. It is concluded that tamoxifen has many and diverse effects on sex hormone levels, and its adverse effects do not affect the biological status of the patient, except perhaps for oestradiol, that increases in some cases, whose possible effect must be studied.

Aged↗

Relapsing Wegener's granulomatosis: successful treatment with cyclosporin-A.

We describe the case of a 32-year-old splenectomised man with severe Wegener's granulomatosis which was refractory to conventional treatment with oral cyclophosphamide and prednisolone. Remission was temporarily induced only with plasma exchange or i.v. immunoglobulin. Because of frequent relapses of the disease and cyclophosphamide side effects, he was started on treatment with cyclosporin-A and a long lasting remission was achieved.

Adult↗

Clearance pathways of soluble immune complexes in the pig. Insights into the adaptive nature of antigen clearance in humans.

Efficient delivery of immune complexes (ICs) to the mononuclear phagocytic system, and subsequent IC processing, may prevent their potentially harmful effects in other tissues and may also be important in the development of humoral immune responses. In mice, rabbits, and primates, the liver and spleen are the main sites of IC clearance. It has been demonstrated previously that the pulmonary capillaries in the pig are lined with macrophages and that certain particulates, including bacteria, localize to this organ. In this study, we used gamma scintigraphy to explore the sites and kinetics of clearance of soluble IC comprising 123I-labeled hepatitis B surface Ag (HBsAg):porcine anti-HBsAg in the Large White pig. At t = 10 min after i.v. injection, 43 +/- 5% (mean +/- SE) IC localized in the lungs, and 36 +/- 6% counts in the liver. At t = 85 min, values were: lungs, 15 +/- 4% and liver, 29 +/- 2%. Findings were similar following intraarterial injection. Complement depletion resulted in more rapid initial IC clearance (t1/2 = 5 min), reduced lung uptake (23 +/- 3% at 10 min), and impaired IC catabolism. In normal animals, 5 to 7% injected IC bound to PBMCs, but no E binding was seen. A fall in PBMC numbers (46 to 59% of baseline), was observed following IC injection. These findings contrast with our previous observations using analogous IC in humans, in which we did not observe any change in peripheral blood leukocyte counts consequent upon complex processing, suggesting that in humans, Es may function as a buffering system for complement-bearing IC in the circulation, preventing their interaction with leukocytes bearing complement and FcR, and the potential activation of these cells.

Animals↗

Type 1 cryoglobulinaemia associated with a thymic tumour: successful treatment with plasma exchange.

Thymic tumours are associated with a wide range of autoimmune and haematological disorders, notably myasthenia gravis, red cell aplasia, and systemic lupus erythematosus. An association with cryoglobulinaemia has only once been reported previously. In this report we describe a 60-yr-old male patient with a spindle cell thymoma, treated surgically, who also had type 1 cryoglobulinaemia, with severe peripheral circulatory impairment with digital ulceration and a mononeutitis multiplex. The patient has been successfully treated with prednisolone, immunosuppression and plasma exchange.

Combined Modality Therapy↗

The anti-lipid A monoclonal antibody E5 binds to rough gram-negative bacteria, fixes C3, and facilitates binding of bacterial immune complexes to both erythrocytes and monocytes.

Treatment of patients with septic shock using monoclonal antibodies (mAbs) to endotoxin is still controversial. Clinical trials of E5, one of the mAbs directed against the lipid A moiety of lipopolysaccharide (LPS), are currently in progress. The mechanisms of action of this, and other antibodies under clinical evaluation, are, however, poorly understood. In this study we examined in vitro the ways in which E5 interacted with Gram-negative bacteria, complement, erythrocytes and monocytes. By fluorescence-activated cell sorter (FACS) analysis we showed direct, dose-dependent binding of E5 to Escherichia coli (E. coli) and Salmonella minnesota (S. minnesota). Antibody binding to S. minnesota was enhanced by treatment with the beta-lactam antibiotic amoxycillin, but not by treatment with the aminoglycoside gentamicin. Immune complexes formed between E5 and both species of Gram-negative bacteria activated both classical and alternative complement pathways, but only in the case of S. minnesota did this facilitate binding to erythrocyte CR1 and monocyte CR3. Bacterial C3b and iC3b fixation by E5 was quantified using specific mAbs. These observations suggest that E5 may enhance bacterial clearance in several ways: (1) by facilitating direct complement fixation; (2) by facilitating the binding of opsonized bacteria to cells of the mononuclear phagocyte system; (3) by enabling bacteria to bind to erythrocyte CR1 (CD35), allowing safe carriage in the circulation to the fixed macrophages of the liver and spleen; (4) by acting synergistically with beta-lactam antibiotics.

Anti-Bacterial Agents↗

Hereditary complement factor I deficiency.

We describe four cases (from three families) of hereditary factor I deficiency, bringing the total number of cases now reported to 23. In one family there are two affected siblings: one has suffered recurrent pyogenic infections; the other is asymptomatic. In the second family, the patient had recurrent pyogenic infections and a self-limiting vasculitic illness; in the third family, the patient suffered recurrent pyogenic and neisserial infections. All four patients had markedly reduced concentrations of C3 in the serum (family 1 propositus: 28%; family 1 asymptomatic sibling: 15%; family 2: 31%; and family 3: 31% normal human serum) which was in the form of C3b. Low IgG2 levels may occur in primary C3 deficiency, and a reduction in IgG2 concentration to 1.14 g/l (normal: 1.30-5.90 g/l) was found in the patient from family 2. Using radioligand binding assays, we demonstrated increased binding of C3b to erythrocytes in a patient with factor I deficiency. This C3b could not be cleaved by autologous serum but could be cleaved by normal serum or purified factor I. We review and compare the published cases of C3, factor H and factor I deficiency.

Adolescent↗

Hereditary C1q deficiency and systemic lupus erythematosus.

We describe a 27-year-old women with systemic lupus erythematosus, C1q deficiency and cytomegalovirus retinitis. She suffered from severe SLE, with cutaneous and CNS involvement, and died of CNS disease aged 28. Review of 29 other published cases of C1q deficiency shows that SLE in these patients is often severe (five with CNS disease, ten with glomerulonephritis). The results of autoantibody studies in this and another patient with C1q deficiency and SLE are presented--both patients had autoantibodies to the extractable nuclear antigens, Sm, RNP and Ro, and one patient had high titres of antibodies to dsDNA. One of the patients had previously been treated with fresh frozen plasma, and antibodies to C1q were present in his serum. Homozygous C1q deficiency is associated with a very high prevalence of severe SLE with the full panoply of autoantibodies characteristic of this disease.

Adult↗

Buerger's disease and protein S deficiency: successful treatment with prostacyclin.

In this report we describe a female patient who presented with peripheral circulatory impairment. She had previously been thought to have a systemic vasculitis, but had failed to respond to corticosteroid and immunosuppressive therapy. Serologic investigations were negative. The patient was a very heavy smoker, and it became clear that her condition had many of the clinical features of Buerger's disease (thrombangiitis obliterans). The diagnosis was confirmed by angiography, and a coagulation screen showed her to have associated protein S deficiency. Her symptoms responded rapidly to cessation of smoking, warfarin therapy, and a series of intravenous prostacyclin infusions. We discuss in detail the possible pathologic mechanisms which might explain the association of protein S deficiency and thrombangiitis obliterans.

Adult↗