Clinical significance of thyrotropin measurement by immunoradiometric assay and thyrotropin-releasing hormone test

The levels of serum TSH were measured by a sensitive immunoradiometric assay (IRMA) method and the responses of TSH to TRH stimulation were observed in three groups of hyperthyroidism, primary hypothyroidism and secondary hypothyroidism. The levels of serum TSH were found to be undetected in 98% (1/51) of the patients with hyperthyroidism, very high in 100% (35/35) of the patients with primary hypothyroidism and normal in 91% (30/33) of the patients with secondary hypothyroidism. TRH test showed no responses of TSH in all patients with hyperthyroidism, high responses in all patients with primary hypothyroidism and blunt responses in 69% (11/16) of patients with secondary hypothyroidism. The results indicate that the measurement of serum TSH by IRMA is a sensitive index in the diagnosis of hyperthyroidism and primary hypothyroidism, but can not be differentiated the secondary hypothyroidism from normal conditions. TRH test may be helpful in the differential diagnosis between secondary hypothyroidism and normal conditions.     

Exophthalmometry and thyroid disease. The value of the Hertel measurement evaluated by a group of patients with thyroid diseases and a control group

Exophthalmometry values from routine referrals to a hospital eye clinic are analysed, including adult patients with and without thyroid disease. In thyroid disease without eye motility complaints (n = 90) the median exophthalmometry value was 18 mm (range 12-28 mm). Thyroid patients with eye muscle involvement (diplopia, n = 47) had significantly higher values (median 22 mm, range 15-31 mm) but did not differ significantly from a subgroup of 51 patients without thyroid disease, but with "big eyes" as a (presumably) physiological finding (median value 20 mm, range 16-25 mm). The above three categories were all excluded from the control group (n = 203) which had 16 mm as median value, range 11-23 mm. Mean values were 16.0 +/- 1.8 mm in the females and 16.5 +/- 2.3 mm in the male controls. A side difference in exophthalmometry value > or = 2 mm appeared in 34% of thyroid patients with eye muscle involvement. This appeared in only a few per cent in the three other groups. Due to the wide overlap between groups, the solitary exophthalmometry reading is of limited diagnostic value, while the importance of exophthalmometry is evident when following the individual patient with orbital disease.     

Post-operative thyroid status of patients with Graves'' disease is determined by the responsiveness of thyrocyte to TSH under the present thyroid gland remnant

OBJECTIVE: Differences in the perspectives of severely and persistently ill patients, their family members, and clinical care providers on key aspects of community-based care were examined to help inform community service planning and development. METHODS: A sample of 183 patients being considered for relocation from psychiatric facilities in Alberta, Canada, to community-based care, were interviewed, as were their primary clinical care providers. Family members of 130 patients were also interviewed. RESULTS: Among the 130 patient-family pairs, 41 percent disagreed about the desirability of relocation, with fewer patients favoring relocation than families. Forty-nine percent of the pairs disagreed about the desired proximity to the family of the relocated patient, with the patient desiring closer proximity than the family member in about half of these cases. Fifty-three percent of the pairs disagreed about the amount of financial and emotional support that the family would provide after relocation. In half of these cases, patients believed the family would provide a higher level of support than the family indicated it could. Among the patients, 49 percent preferred independent living, whereas only 10 percent of family members and 17 percent of clinical care providers preferred it. Fifty-five percent of patients expressed a clear desire to work, whereas care providers believed that only 12 percent of patients were employable. CONCLUSIONS: Persistently mentally ill residents of psychiatric facilities express clear preferences about key aspects of community-based care when they are asked, and these preferences often reflect different views from those expressed by either family members or clinical care providers.     

Quantification of salmon alpha- and thyrotropin (TSH) beta-subunit messenger RNA by an RNase protection assay: regulation by thyroid hormones

Brightness discrimination of black-white stimuli (1-37 Cd/m; CIE-31 chromatic coordinate X = 0.340, Y = 0.304) were studied using choice conditioning paradigm in two monkey (Macaque Rhesus). Confusion matrices were composed of probabilities of instrument responses to conditioned and differential stimuli in ten series in which one of the ten intensities was employed as a conditioned one. Confusion matrices were transformed into the correlation matrices between the vectors corresponding to the stimuli. Factor analysis of correlation matrices revealed two-dimensional circular structure of monkey's brightness perceptual space. This space was principally similar with that in humans, fishes, and rabbits. Two eigenvectors which constituted two-dimensional Euclidean space of brightness can be interpreted as bright and dark neuronal channels.     

Expression of the human TSH receptor in a human thyroid carcinoma cell line that lacks an endogenous TSH receptor: growth inhibition by cAMP

The sexually dimorphic pattern of GH secretion regulates the expression of several steroidogenic enzymes in rat liver, including a male-specific 3 beta-hydroxysteroid dehydrogenase/delta 5-->4-isomerase (3 beta HSD). Recently, we identified male-specific isoforms of immunoreactive 3 beta HSD in mouse liver [42 kilodaltons (kDa)] and gonads (47 kDa). To test whether GH can regulate the expression of these murine 3 beta HSDs, endogenous forms of 3 beta HSD were studied in transgenic mice expressing heterologous GH transgene products. Mice from five transgenic lines were used; two expressed GH transgenes encoding the phosphoenolpyruvate carboxykinase (PEPCK) promoter fused to either the human (h) GH (somatogenic and lactogenic) or bovine (b) GH (somatogenic) structural genes, and three expressed GH transgenes encoding the mouse metallothionein-1 (MT1) promoter fused to the hGH, hGH variant (hGHv), or bGH structural genes. Control mice were normal nontransgenic littermates. Expression of a male-specific (42 kDa) isoform of hepatic 3 beta HSD is dramatically suppressed in all transgenic mouse lines, as detected on Western immunoblots, without affecting a 47-kDa isoform expressed in livers of both male and female mice. This negative regulation was not observed in mouse kidney, which normally expresses two 3 beta HSD isoforms (in both sexes) with molecular masses similar to those in liver. Considering that PEPCK and MT1 promoters direct expression of GH fusion genes in both tissues, the inhibition of hepatic, but not renal, 3 beta HSD immunoreactivity suggests that GH affects sex-specific, rather than tissue-specific, expression of 3 beta HSD. As in the liver, sex-specific expression of 3 beta HSD in the testis is also suppressed by heterologous GH, but with one notable difference. Only human-derived GH (MT1-hGH and MT1-hGHv) effectively inhibits expression of the 47-kDa sex-specific isoform of testicular 3 beta HSD, without affecting the 44-kDa isoform expressed in gonads of both male and female mice. These results suggest that the negative effects of heterologous GH on sex-specific 3 beta HSDs may be mediated by PRL receptors in the testis and GH receptors in the liver. PEPCK-GH transgenes had little effect on testicular 3 beta HSD, possibly because this promoter (unlike MT1) is relatively inactive in this tissue. In the liver of male transgenics (PEPCK-hGH), loss of the sex-specific (42-kDa) 3 beta HSD has little effect on the Km for dehydroepiandrosterone (DHEA; 11 microM) compared with that in normal controls (16 microM).(ABSTRACT TRUNCATED AT 400 WORDS)     

Use of a rapid intraoperative parathyroid hormone assay in the surgical management of parathyroid disease

We present recent developments in the area of glycosaminoglycans (GAGs) and their possible interaction with insulin-like growth factor-I (IGF-I). GAGs are constituents of proteoglycans, and the combination of a core protein and a specific GAG makes a unique proteoglycan with a precise developmental pattern and with the ability to bind growth factors. This process is apparently regulated by the moiety of the peripheral GAGs. The supplementation of GAGs promotes neuritogenesis in vitro and stimulates nerve regrowth and muscle reinnervation, an effect correlated with an increase in trophic factor mRNA expression. In the case of neonatal nerve lesion, there is in addition an enhanced motor neuron survival, accompanied by higher levels of IGF-I in plasma and denervated muscle. The neurotrophic and neuroregenerative effects of exogenous GAGs were also observed in motor neuron disease in the wobbler mouse.     

Evidence for the effect of antibodies to TSH receptors on the thyroid ultrasonographic volume in patients with Graves' disease

OBJECTIVE: It has been demonstrated that antibodies (Ab) to thyroid-stimulating hormone receptors (R), which stimulate the thyroid gland, induce hyperthyroidism in patients with Graves' disease. Furthermore, it has been shown in thyroid cells in culture that thyroid-stimulating hormone receptor Ab acts through the adenosine 3', 5'-monophosphate pathway which stimulates both thyroid hormonogenesis and growth. We investigated the relations between thyroid autoimmunity expression and thyroid ultrasonographic parameters or thyroid hormonal status in patients with Graves' disease. PATIENTS: A prospective study of 53 consecutive patients referred with untreated Graves' disease. MEASUREMENTS: Measurements were made of serum TSH-R, peroxidase (TPO) and thyroglobulin (Tg) Ab and basal plasma free T4 (FT4), free T3 (FT3) and TSH. Thyroid morphological characteristics (number and total volume of nodule(s), total volume of lobes and total thyroid volume) were determined by ultrasonography. RESULTS: There were significant correlations (P < 0.001) between TSH-RAb levels and FT4 values (r = 0.48) or FT3 levels (r = 0.46). Likewise, significant correlations were found between TSH-RAb levels and total lobe volume values (r = 0.56, P < 0.001), total nodular volume values (r = 0.59, P < 0.01) or total thyroid volume values (r = 0.63, P < 0.001). By contrast, no correlation was found between TSH-RAb levels and the number of nodules or between any of the ultrasonographic parameters and TPOAb levels or TgAB values. CONCLUSIONS: This study demonstrates, in vivo, that TSH receptor antibodies modulate the thyroid ultrasonographic extranodular and nodular volumes in patients with Graves' disease.     

The expression of the urinary forms of human luteinizing hormone beta fragment in various populations as assessed by a specific immunoradiometric assay

Human gonadotrophins undergo metabolic transformations which result in the presence of several smaller, structurally and immunologically related forms of gonadotrophins in the urine. For luteinizing hormone (LH), a beta core fragment (LHbeta cf) has been isolated from the pituitary and characterized. The corresponding urinary fragment is inferred from mass spectral and immunochemical analysis of chromatographically separated urinary forms. Physicochemical characteristics, primarily mass spectral and chromatographic, indicate that the pituitary and urinary forms of LHbeta cf have a different structure, probably in the carbohydrate moieties. This communication characterizes the expression of LHbeta cf in the urine of both reproductive and post-reproductive age women and in men, employing assays highly specific for the pituitary form of the fragment. It was found that LHbeta cf is the predominant LH associated molecular form in the urine during peri-ovulatory period, peaking 1-3 days later than intact LH and reaching a concentration of approximately 600 fmol/mg creatinine, 7-fold higher than either LH or LH free beta subunit. Corresponding concentrations of human chorionic gonadotrophin (HCG) beta cf were <1% that of LHbeta cf. LHbeta cf cross-reaction with some LH or LHbeta monoclonal antibodies may well interfere with the accurate estimation of the day of the LH surge when urinary tests are utilized.     

The use of fine needle aspiration biopsy in the management of thyroid disease

Fine needle aspiration biopsy is now a first line investigation in thyroid disease. The purpose of this study was to evaluate the results of this technique in comparison with routine histopathology. A total of 593 aspirations over a four year period were included. There were 390 (65.7%) solitary nodules, 124 (20.9%) multinodular goiters, 66 (11.1%) diffuse goitres and 13 (2.2%) recurrent post thyroidectomy nodules. Radioisotope scanning in 386 cases showed 325 (84.2%) cold nodules, 54 (14.0%) warm nodules and 7 (1.8%) hot nodules. There were 458 (77.2%) colloid goitres and cysts, 14 cases of thyroiditis (2.2%) and 30 malignancies diagnosed on fine needle aspiration biopsy. In 19 cases (3.2%) a diagnosis of follicular neoplasm and in 29 cases (4.9%) a diagnosis of suspicious aspirate was made. Histological results were available in 176 cases. In 108 cases findings of histology and FNAB were compared with radioisotope scanning. A sensitivity of 92.8% and 42.8%, a specificity of 90.1% and 98.7% and accuracy index of 90.3% and 94.3% was found, when considering suspicious cases alternatively as positives and negatives. Surgery was recommended in all suspicious cases to prevent reduction in sensitivity of the technique. Fine needle aspiration biopsy was found to be a highly effective procedure which can obviate a lot of unnecessary surgery in thyroid lesions.     

TSH receptor and Gs-alpha gene mutations in the pathogenesis of toxic thyroid adenomas--a note of caution

The detection of a constitutive activation of the AC cascade by TSH-R and Gs alpha mutations in a number of TTAs should not distract from the large gap in our understanding of the pathogenesis of thyroid tumors. TTAs form only a minor fraction of all thyroid nodules, and even within this small subgroup, activating mutations have been found regionally with a highly variable incidence. If activating mutations were the sole and only cause of TTAs, a homogeneous functional and morphological response of all thyrocytes would ensue. This, however, is not the case. Rather, severe disturbances of the Gs protein-AC cascade regularly occur in TTAs. Even within thyroids affected by activating TSH-R germline mutations, some cell clones proliferate at a faster rate than others, causing nodular growth with time. Moreover, not only functional, but also morphological heterogeneity very frequently evolves even in clonal adenomas. The natural heterogeneity among individual thyrocytes may account for a different functional and proliferative response among cells affected by identical mutations or any other gain-of-function event. The recent findings in toxic adenomas must be taken together with the fact that, in the large majority of all thyroid nodules, iodine metabolism is by no means enhanced, but diminished or absent and that, in this type of tumor, no consistent pattern of growth-stimulating mutational events has yet been identified. The nature, the precise temporal sequence and interaction of the genetic, cytogenetic, and environmental events that cause the very common and often autonomous nodular growth of only a few distinct cell populations within the human thyroid gland remain largely unknown.     

Comparison between oral and written spelling in Alzheimer's disease

Written and oral spelling were compared in 33 patients with Alzheimer's disease (AD) and 25 control subjects. AD patients had poorer spelling results which were influenced by orthographic difficulty and word frequency, but not by grammatical word class. Lexical spelling was also more deteriorated than phonological spelling. Moreover, oral spelling was more impaired than written spelling in AD patients, whereas no difference was present between oral and written spelling of controls. Analysis of spelling errors showed that, for controls, errors were predominantly phonologically accurate in both spelling tasks. Significantly, AD patients produced more phonologically accurate than inaccurate errors in written spelling, whereas these errors did not differ in oral spelling. In contrast to controls who produced more constant than variable responses in oral and written spelling, AD patients made more variable responses (words correctly spelled in one task but incorrectly in the other) and they showed many instances of variable errors (different misspellings from one spelling task to the other). Two stepwise regression procedures showed that written misspellings were specifically correlated with language impairment, whereas oral spelling errors were correlated with attentional and language disorders. These results suggest that AD increases the attentional demands of oral spelling process as compared to written spelling. This dissociation argues, either for a unique Graphemic Buffer in which oral spelling requires more attentional resources than written spelling or for the hypothesis of separate buffers for oral and written spelling.     

颈椎椎弓根标本与CT图像测量椎弓根相关径线结果的比较

目的:比较颈椎椎弓根标本与CT图像测量椎弓根相关径线的差异,为临床颈椎椎弓根置钉手术前CT图像对椎弓根相关径线测量结果的临床应用提供依据.方法:分别在27具中国成人干燥颈椎(C3～C7)标本和CT图像上测量椎弓根高度(PH、PH′)、宽度(PW、PW′)、椎弓根轴线的骨性通道全长(TL、TL′)、两种椎弓根长度(PL1、PL2,PL1′、PL2′)进行线性测量,比较标本测量结果与CT测量结果两组数据的差异.结果:在同侧颈椎标本或CT图像上,不同节PW(PW′):C3、C4＜C5、C6(P<0.05),C5、C6＜C7(P<0.01);PH(PH′):各节之间差异无统计学意义;TL、PL1和PL2(TL′、PL1′和PL2′):不同节间差异无统计学意义;在同一颈椎标本或CT图像上,相同节段PW(PW′)＜PH(PH′)(P<0.01﹚,PL1(PL1′)＜PL2(PL2′)(P<0.01).CT图像上各径线的测量值与对应标本测量值差异无统计学意义(P>0.05).结论:颈椎标本与CT图像测量椎弓根相关径线结果无明显差异,提示术前CT图像测量对颈椎成功置钉手术可提供可靠的参考依据.     

Radiotherapy in the management of thyroid cancer

Surgery is the definitive and potentially curative treatment for the slow growing well-differentiated papillary and follicular carcinomas. Total (or near-total) thyroidectomy is required, together with excision of adjacent lymph nodes when involved, or a modified block dissection if there is extensive lymphatic involvement. Ablation of residual normal thyroid with radioactive iodine usually follows as this will permit subsequent whole-body I-131 scanning to exclude the presence of residual or metastatic disease. Normally such patients have an excellent prognosis and can be followed simply with serum thyroglobulin estimations. Occasionally therapeutic radioactive iodine is necessary to eradicate metastatic disease. The anaplastic carcinomas grow and metastasise with explosive rapidity. They are typically inoperable at presentation and have no ability to concentrate iodine. Prognosis is appalling with external beam radiotherapy providing only palliation. Medullary carcinoma is different again as it arises from the parafollicular or C-cells. Total thyroidectomy must be undertaken as these tumours may be multifocal; a central compartment neck resection is ideally undertaken at the same time, together with a formal block dissection if lymph node disease is found to be present. External beam radiotherapy is often required. These tumours can be inherited and produce the tumour marker calcitonin. The rarest group of thyroid cancer is the lymphomas. Like the anaplastic carcinomas, they grow very rapidly but, unlike the former, are radio-responsive. The additional use of chemotherapy is necessary when they are of advanced stage or demonstrate poor prognostic factors.     

Comparison of a radioallergosorbent (RAST) inhibition method and a monoclonal enzyme linked immunosorbent assay (ELISA) for aeroallergen measurement

BACKGROUND: Mouse and rat urinary proteins are potent occupational allergens for exposed personnel. Methods of measuring airborne allergens differ greatly, and reported levels of allergens vary considerably between laboratories. OBJECTIVES: To compare the values obtained using two different methods of allergen detection. METHODS: Air samples were collected in rat rooms in Sweden and the United Kingdom at 2 L/min on to polytetrafluoroethylene (PTFE) filters and extracted in buffer containing 0.5% v/v Tween 20. Airborne rat urinary allergen (RUA) was measured in all samples by both RAST inhibition using a polyclonal human serum pool (UK) and a two monoclonal antibody sandwich ELISA employing antibodies specific for Rat n 1.02 (alpha2u-globulin) (Sweden). RESULTS: The two methods gave values which were correlated (r2 log values = 0.72, P<0.0001), but differed by several orders of magnitude (median [range] ratio of RAST inhibition/ELISA = 316 [7-26(80)]. There was a systematic bias: as the absolute values increased, the difference in the measurements increased. The rat urine standards used were antigenically similar. CONCLUSIONS: A large contrast in RUA values obtained from the two assays was observed in this study. This may be primarily due to methodological differences, but variations in antibody specificities or composition of allergenic epitopes in the air samples may contribute. The results demonstrate that standardization of methods and antibodies is necessary before interlaboratory comparisons can be made.     

Thyrotropin assay by chemiluminescence in the diagnosis of dysthyroidism with low thyrotropin and normal thyroid hormones levels

The performances of a new "3rd generation" chemoluminescence TSH assay (TSH ICMA) with a functional sensitivity of 0.005 mU/l were compared with those of an "ultrasensitive" TSH immunoradiometric assay (TSH IRMA) in a series of patients characterised by a TSH IRMA less than 0.20 mU/l and normal free thyroxin (T4 L) and triiodothyronine (T3 L) concentrations. The 95% cut-off value for hyperthyroidism was 0.03 for TSH ICMA and 0.05 for TSH IRMA. In a first group of 41 subjects undergoing Tc99m thyroid scan, images of multifocal increased uptake or toxic adenoma were associated with a lower TSH ICMA than in patients with a normal isotope scan. TSH ICMA was also lower than TSH IRMA (p < 0.01). At the cut-off value of 0.03 mU/l, the specificity of TSH ICMA was higher than that of TSH IRMA, but the sensitivity were identical. In a second group of 36 patients with severe non-thyroid diseases, TSH ICMA was lower than the cut-off value for hyperthyroidism in 30% of cases, while TSH IRMA was lower than the cut-off value in 40% of cases. A satisfactory concordance was observed between the two methods. In conclusion, the two TSH assays, IRMA and ICMA, provide globally comparable information in subjects with a low TSH and normal T4 L and T3 L. However, the better specificity of TSH ICMA and a smaller overlap with the frank hyperthyroid zone in patients with non-thyroid disease argue in favour of the use of this new assay method.     

An in vitro force measurement assay to study the early mechanical interaction between corneal fibroblasts and collagen matrix

An in vitro force measurement assay has been developed to quantify the forces exerted by single corneal fibroblasts during the early interaction with a collagen matrix. Corneal fibroblasts were sparsely seeded on top of collagen matrices whose stiffness was predetermined by micromanipulation with calibrated fine glass microneedles. The forces exerted by individual cells were calculated from time-lapse videomicroscopic recordings of the 2-D elastic distortion of the matrix. In additional experiments, the degree of permanent reorganization of the collagen matrices was assessed by lysing the cells with 1% Triton X-100 solution at the end of a 2-hour incubation and recording the subsequent relaxation. The data suggest that a cell can exert comparable centripetal force during either extension of a cell process or partial retraction of an extended pseudopodia. The rates of force associated with pseudopodial extension and partial retraction were 0.180 +/- 0.091 (x 10(-8)) N/min (n = 8 experiments) and 0.213 +/- 0.063 (x 10(-8)) N/min (n = 8 experiments), respectively. Rupture of pseudopodial adhesion associated with cell locomotion causes a release of force on the matrix and a complete recoil of the pseudopodia concerned; a simultaneous release of force on the matrix was also observed at the opposite end of the cell. Lysis of cells resulted in 84 +/- 18% relaxation of the matrix, suggesting that little permanent remodeling of matrix is produced by the actions of isolated migrating cells.