Association between Hashimoto's thyroiditis and melanoma: a retrospective matched cohort study.

An inflammatory microenvironment has been shown to increase risk for malignant melanoma, suggesting that melanoma may be related to a pro-inflammatory state. Though Hashimoto's thyroiditis is one of the most common autoimmune diseases, there are no investigations of its relationship with melanoma. We aim to determine if Hashimoto's increases risk of developing melanoma. A retrospective, validated cohort of patients with a diagnosis of Hashimoto's between 2005 and 2020 were identified using the Olmsted County database. Patients were age and sex matched to controls without a Hashimoto's diagnosis. The primary outcomes were development of melanoma and time to first melanoma diagnosis. 4805 patients were included in the study, with 1726 (36%) having a diagnosis of Hashimoto's. Hashimoto's patients had no significant difference in risk of melanoma (relative risk 0.96, 95% CI 0.78-1.17) or nonmelanoma skin cancer (relative risk 0.95, 95% CI 0.86-1.06) compared with matched controls. This suggests that the local proinflammatory environment present in Hashimoto's does not contribute significantly to melanoma risk. Larger studies may be needed to further characterize the relationship between these diseases.

Lisina digestível na ração de frangos de corte tipo caipira na fase de crescimento / Dietary digestible lysine in free-range broiler chickens during the growth phase

O presente experimento foi conduzido para determinar as exigências de lisina digestível para frangos de corte (linhagem Redbro), machos e fêmeas, durante o período de crescimento. Foram utilizados 630 frangos, alojados em 30 boxes com acesso à área de pastejo. O delineamento experimental utilizado foi o inteiramente ao acaso, em esquema fatorial 5x2 (lisina e sexo), e três repetições com 21 aves cada. Os níveis de lisina digestível avaliados foram: 7,07; 8,07; 9,07; 10,07 e 11,07g/kg. Avaliou-se o consumo de lisina, o consumo de ração, o ganho de peso e a conversão alimentar. Observou-se efeito de interação (P<0,05) entre os níveis de lisina e sexo para o ganho de peso. Houve efeito (P<0,01) dos níveis de lisina sobre o consumo de lisina, o ganho de peso e a conversão alimentar. Verificou-se que todas as variáveis foram influenciadas (P<0,05) pelo sexo dos frangos. Recomendam-se 10,08 e 9,49g de lisina digestível/kg de ração, correspondendo ao consumo estimado de 21 e 20g de lisina, para machos e fêmeas, respectivamente, para melhor ganho de peso das aves. Para melhor conversão alimentar, recomendam-se 9,61g de lisina digestível/kg, para frangos de ambos os sexos, correspondendo ao consumo estimado de 20g de lisina.(AU)

This experiment was conducted to determine the requirements of digestible lysine in male and female free-range broiler chickens (Redbro lineage) during the growth phase. Six hundred and thirty broiler chickens were allocated in 30 pens with access to the pasture area. The experimental design was completely randomized in a 5x2 (lysine and gender) factorial arrangement with 3 repetitions with 21 chickens each. The levels of digestible lysine evaluated were: 7.07, 8.07, 9.07, 10.07 and 11.07g/kg. The performance traits evaluated were lysine intake, feed intake, weight gain and feed conversion ratio. An interaction effect (P<0.05) was observed between dietary lysine level and gender for body weight gain. There was an effect (P<0.01) of the levels of lysine on lysine intake, body weight gain and feed conversion ratio. It was found that all the variables were affected (P<0.05) for the gender of chickens. We recommended 10.08 and 9.49 g of digestible lysine/kg diet, corresponding to the estimated intake of 21 and 20g of lysine, for males and females, respectively, for better body weight gain of chickens. For better feed conversion ratio, the recommendation is of 9.61 g of lysine/kg of diets, for chickens of both genders, corresponding to the estimated intake of 20g of lysine.(AU)

Modelos de norma de reação para estudo das características de qualidade da carne de codornas de corte em função das razões (metionina + cistina): lisina da dieta / Reaction norm models for the study of meat quality of european quail in function of (methionine + cysteine): lysine diet ratio

Objetivou-se avaliar a sensibilidade dos valores genéticos para características de qualidade da carne em codornas de corte alimentadas com dietas contendo diferentes relações de (metionina + cistina): lisina, do nascimento aos 21 dias de idade, por meio de modelos de normas de reação. Utilizaram-se 9011 informações de qualidade de carne referentes a 1400 progênies de 80 reprodutores e 160 matrizes de duas linhas (LF1 e LF2). Para o ajuste dos modelos de regressão aleatória, foi usado o programa WOMBAT, considerando-se nas análises homogeneidade de variância residual. As codornas foram alimentadas do nascimento aos 21 dias de idade com dietas contendo as relações 0,61; 0,66; 0,71; 0,76 e 0,81 de (metionina + cistina): lisina, mantendo os níveis de proteína bruta de 26,12% e de energia em 2900 kcal EM/kg da dieta. Dos 22 aos 35 dias de idade, todas as codornas foram alimentadas com dieta contendo 22% de proteína bruta e 3050 kcal EM/kg da dieta. As estimativas da variância genética e da herdabilidade foram influenciadas pelo gradiente ambiental e pela linha, com mudanças nessas estimativas com o aumento do gradiente ambiental. Os valores genéticos das características de qualidade de carne referentes a cada uma das linhas se alteraram com o aumento das relações de aminoácidos das dietas em razão das mudanças no ordenamento dos valores genéticos, evidenciando a existência da interação genótipo x nível de relação dos aminoácidos da dieta para características de qualidade de carne. Predições de valores genéticos de características de qualidade de carne com base em determinada relação de (metionina + cistina): lisina da dieta não são válidas para outras relações desses aminoácidos.

This study aimed to evaluate the sensitivity of breeding values for meat quality traits of European quails fed different (methionine + cystine): lysine ratio diets from hatch to 21 days of age, using reaction norm models. A total of 9011 meat quality records from 1400 progenies of 80 sires and 160 dams from two lines (LF1 and LF2) were used in the analyses considering homogeneity of residual variance. The quails from hatch to 21 days of age were fed diets containing 0.61, 0.66, 0.71, 0.76 and 0.81 (methionine + cystine): lysine ratios, 26.12% of crude protein and 2900 ME/kcal of diet. From 22 to 35 days of age all quail were fed a diet containing 22% of crude protein and 3050 kcal ME/kg of diet. The random regression model analyses was performed using the WOMBAT program considering homogeneity of residual variance. Genetic variance and heritability estimates were affected by the environment gradient of diet and line, increasing these estimates with the increase of the (methionine + cystine): lysine ratio of the diet. The breeding values changed with the increase of the environment gradient of the diet with changes in the rank of genetic breeding values characterizing the existence of genotype by environment interaction for meat quality traits. Predictions of meat quality trait breeding values based on a given (methionine + cystine): lysine ratio are not valid for other levels of the amino acid ratio.

Características de desempenho e de carcaça em diferentes genótipos de codornas de corte / Performance and carcass traits of different meat type genotypes

Objetivou-se com este trabalho comparar e correlacionar as características de desempenho e de carcaça em codornas de corte do nascimento aos 35 dias de idade. Foram utilizadas 1176 codornas de um dia, machos e fêmeas, de sete genótipos de codornas de corte (EV1, EV2, UFV1, UFV2, UFV3, LF1 e LF2), distribuídas em delineamento inteiramente ao acaso, com ensaio fatorial 7x2 (genótipo x sexo), em sete repetições com 12 codornas por unidade experimental. As codornas foram pesadas individualmente do nascimento aos 35 dias de idade, em intervalos semanais. Aos 35 dias de idade, dois machos e duas fêmeas de cada genótipo e repetição foram amostrados e abatidos para avaliação do peso de carcaça e dos cortes nobres. As análises estatísticas foram conduzidas utilizando-se o procedimento GLM e CORR com a opção MANOVA do SAS para avaliar as diferenças entre os genótipos e a correlação entre as variáveis. Não houve interação (P≥0,05) entre genótipo e sexo para as características de desempenho (peso e ganho de peso nas diferentes idades). Entretanto, houve efeito significativo da interação genótipo x sexo (P<0,05) para as características de pesos de carcaça, peito e coxa+sobrecoxa. Em geral, as codornas dos grupos genéticos UFV1, UFV2 e UFV3 foram as mais pesadas dos sete aos 35 dias de idade e apresentaram maiores rendimentos de carcaça. Como observado pelas correlações fenotípicas, a tendência é que codornas que apresentam maior peso corporal e ganho de peso irão apresentar maior peso de carcaça e dos seus principais cortes.(AU)

This study was carried out to compare and relate the performance and carcass traits of different quail genotypes from hatch to 35 days of age. A total of 1176 one-day-old quails of both sexes were allotted in a completely randomized experimental design, in a 7x2 factorial scheme (genotypes x sexes), in seven replicates with 12 quails per experimental unit. Quails of each genotype were weighed weekly from hatch to 35 days of age. At 35 days of age two males and two females of each genotype and replicate were sampled and slaughtered to evaluate carcass weight and main cut yield. Statistical analyses were performed by GLM and CORR procedure from the Statistical Analysis System (SAS, 2000, version 9.0), with the MANOVA option of the SAS device to assess the differences between the genotypes and the correlation between variables. There was no interaction (P≥0.05) between genotype and sex with the performance characteristics of weight and weight gain. However, there was a significant effect of genotype x sex (P<0.05) for the characteristics carcass,breast, thigh and drumstick weights. In general, quails of genetic groups UFV1, UFV2 and UFV3 were heavier from 7 to 35 days of age. We observed that for the correlation the tendency is that quail that showed higher body weight and weight gain will have greater housing and main cuts weight.(AU)

Integrated biological responses of zebrafish (Danio rerio) to analyze water quality in regions under anthropogenic influence.

This study analyzed water quality in regions around Patos lagoon (Southern Brazil) that are under anthropogenic pressure. Water samples were collected from five different sites, including one used as a source for human consumption (COR) and others known to be influenced by human activities (IP). Danio rerio (Teleostei, Cyprinidae) organisms were exposed for 24h to these water samples, plus a control group. It was observed that: (1) reactive oxygen species levels were lower in COR and IP than in the control group; (2) glutamate-cysteine ligase (catalytic subunit) expression was higher in COR than in other sites; (3) exposure to all water samples affected long-term memory (LTM) when compared to control group. Thus, some water samples possess the ability to modulate the antioxidant system and to induce a decline in cognitive functions, as measured by LTM. The obtained results indicate that a combination of variables of different organization level (molecular, biochemical and behavioral) can be employed to analyze water quality in impacted regions.

Optical, structural and electrical investigations of TiO2/multi-walled carbon nanotube composites.

Nanocomposites of TiO2 and multi-walled carbon nanotubes (MWNTs) were produced by the addition of different concentrations of MWNTs to a TiO2 sol matrix. Conductive coatings were prepared by spin coating the nanocomposite sols on glass substrates and sintering the samples at 300 degrees C for 15 min. No crystalline phase of TiO2 was formed at this temperature. The sheet resistance of the coatings was decreased from some hundreds of Momega/sq to just a few komega/sq by the addition of MWNTs to the TiO2 matrix. Moreover, sintering of the coatings in a reducing atmosphere has lead to a lower sheet resistance than that presented by coatings sintered in air. The lowest resistivity of 2.0 x 10(-1) omega x cm was obtained by coatings prepared with 5.0 mg/ml MWNTs in the composite sol. The optical, structural and electrical properties of the coatings were correlated and demonstrated.

Structure, wettability and photocatalytic activity of CO(2) laser sintered TiO(2)/multi-walled carbon nanotube coatings.

Nanocomposites of titanium dioxide (TiO(2)) and multi-walled carbon nanotubes (MWNTs) were prepared and deposited by sol-gel spin coating on borosilicate substrates and sintered in air at 300 °C for 15 min. Further irradiation of the films with different CO(2) laser intensities (4.3-17 W m(-2)) was carried out in order to crystallize TiO(2) in the anatase form while preserving the MWNT's structure. The laser irradiation changed the crystal structure of the coatings and also affected the wettability and photocatalytic activity of the films. The anatase phase was only observed when a minimum laser intensity of 12.5 W m(-2) was used. The contact angle decreased with the enhancement of the laser intensity. The photocatalytic activity of the films was determined from the degradation of a stearic acid layer deposited on the films. It was observed that the addition of carbon nanotubes themselves increases the photocatalytic activity of TiO(2) films. This efficiency is even improved when high CO(2) laser intensities are used during the sintering of the coatings.

On carbide dissolution in an as-cast ASTM F-75 alloy.

The solution treatment of an as-cast ASTM F-75 alloy was investigated. Microstructural evolution was followed during thermal processing, in particular with regard to the content and type of carbides formed. To evidence any probable carbide transformations occurring during the heating stage, as well as to clarify their effect on the carbide dissolution kinetics, three heating rates were studied. Image analysis and scanning electron microscopy techniques were used for microstructural characterization. For the identification of precipitates, these were electrolytically extracted from the matrix and then analyzed by X-ray diffraction. It was found that the precipitates in the as-cast alloy were constituted by both a M(23)C(6) carbide and a sigma intermetallic phase. The M(23)C(6) carbide was the only phase identified in solution-treated specimens, regardless of the heating rate employed, which indicated that this carbide dissolved directly into the matrix without being transformed first into an M(6)C carbide, as reported in the literature. It was found that the kinetics of dissolution for the M(23)C(6) carbide decreased progressively during the solution treatment, and that it was sensitive to the heating rate, decreasing whenever the latter was decreased. Because the M(23)C(6) carbide was not observed to suffer a phase transformation prior to its dissolution into the matrix, the effect of the heating rate was associated to the morphological change occurred as the specimens were heated. The occurrence of the observed phases was analyzed with the aid of phase diagrams computed for the system Co-Cr-Mo-C.

Immunohistochemical analysis of sodium iodide symporter expression in metastatic differentiated thyroid cancer: correlation with radioiodine uptake.

The ability of thyroid cancers to concentrate radioiodine (RAI) is dependent, in part, upon the expression and functional integrity of the sodium iodide symporter (NIS). However, some differentiated thyroid carcinomas (DTCs) and most undifferentiated thyroid carcinomas lack the ability to concentrate iodide and are thereby insensitive to 131I therapy. Variation of NIS protein expression may be an important factor in this behavior. We wished to determine whether NIS protein expression in primary DTC tumors correlated with the subsequent RAI uptake by metastatic lesions in the same patients. We obtained paraffin-embedded tissue specimens from 60 patients with metastatic thyroid cancer who had undergone total or near-total thyroidectomy at the Mayo Clinic for DTC and had known presence or absence of RAI uptake in their tumor deposits determined by total body scanning after thyroid hormone withdrawal. Tissue sections from the primary intrathyroidal tumors were subjected to immunostaining (IS) using a monoclonal antibody against human NIS. Slides were subsequently examined for specific IS by two independent reviewers. For each patient, whole body scan (WBS) uptake was recorded, and correlation between results of IS and WBS was analyzed. Of 43 patients with a positive WBS, 37 also had positive IS of their tumors. In six patients with negative IS, a positive WBS was documented, and in three of these cases TSH at the time of surgery was less than 0.3 mIU/liter. Of the 17 patients with negative WBS, 10 were also negative on IS. Positive IS accurately predicted a positive scan in our study in 84% of cases; the ability of the IS to detect all cases with a positive scan was 86%, and it increased to 90% when patients who were receiving thyroid hormone therapy at the time of surgery were excluded from the analysis. Overall, the results of our retrospective study suggest that NIS IS of the thyroidal primary tumor in patients with papillary and follicular thyroid cancers has substantial ability to predict the behavior of subsequent deposits of metastatic and recurrent cancer with respect to iodine trapping and concentration. Our findings require confirmation in prospective studies to more accurately determine the predictive ability of the test and its role in the postoperative management of patients with DTC. If confirmed, NIS IS of DTC primary lesions may prove useful in the management of patients with known or suspected metastatic thyroid cancer.

Renal metastases from thyroid papillary carcinoma: study of sodium iodide symporter expression.

Kidney metastases from thyroid cancer are rare. We report two such patients and demonstrate that the in vivo 131I uptake by the kidney metastasis is associated with high levels of sodium iodide (Na+/I-) symporter (NIS) expression in the first case. Case 1: A 61-year-old woman with papillary thyroid carcinoma-follicular variant (PTC-FV) presented with scapular metastasis. After thyroidectomy and scapulectomy, a 131I posttherapy scan showed left upper quadrant uptake. A 3.0-cm metastatic PTC-FV deposit was removed by partial nephrectomy. Case 2: A 53-year-old woman presented with back pain. A computed tomography (CT) scan showed a 3.5-cm renal mass, a multinodular goiter, and lung metastases thought secondary to a renal cell carcinoma. A unilateral nephrectomy revealed metastatic PTC-FV. After thyroidectomy, a 131I posttherapy scan showed lung and skeletal metastases. NIS immunoreactivity in tumoral tissue was strongly positive in the primary tumor, shoulder, and kidney metastasis in case 1, as well as in the primary tumor in case 2. Spotty, low-level NIS expression was observed in the kidney metastasis in case 2. In conclusion, kidney metastases of PTC-FV may occasionally retain adequate levels of NIS expression, enabling their detection during life. Thus, intense uptake in the abdomen during 131I imaging should not be assumed to be physiological gastrointestinal tract residual radionuclide activity.

Pneumocystis carinii pneumonia, pulmonary tuberculosis and visceral leishmaniasis in an adult HIV negative patient.

This is a case report of a 29 year old male with pneumocystis pneumonia and tuberculosis, and who was initially suspected of having HIV infection, based on risk factor analyses, but was subsequently shown to be HIV negative. The patient arrived at the hospital with fever, cough, weight loss, loss of appetite, pallor, and arthralgia. In addition, he was jaundiced and had cervical lymphadenopathy and mild heptosplenomegaly. He had interstitial infiltrates of the lung, sputum smears positive for Mycobacterium tuberculosis and Pneumocystis carinii, and stool tests were positive for Strongyloides stercoralis and Schistosoma mansoni. He was diagnosed as having AIDS, and was treated for tuberculosis, pneumocystosis, and strongyloidiasis with a good response. The patient did not receive anti-retroviral therapy, pending outcome of the HIV tests. A month later, he was re-examined and found to have worsening hepatosplenomegaly, pancytopenia, fever, and continued weight loss. At this time, it was determined that his HIV ELISA antibody tests were negative. A bone marrow aspirate was done and revealed amastigotes of leishmania, and a bone marrow culture was positive for Leishmania species. He was treated with pentavalent antimony, 20 mg daily for 20 days, with complete remission of symptoms and weight gain. This case demonstrates that immunosuppression from leishmaniasis and tuberculosis may lead to pneumocystosis, and be misdiagnosed as HIV infection. The occurrence of opportunistic infections in severely ill patients without HIV must always be considered and alternate causes of immunosuppression sought.

Expression of the sodium iodide symporter in human kidney.

BACKGROUND: The human sodium iodide symporter (hNIS) is a transmembrane protein that mediates the active transport of iodide in the thyroid gland. Following cloning of NIS, NIS expression has been detected in a broad range of nonthyroidal tissues, suggesting that iodide transport in these tissues is conferred by the expression of functional NIS protein. METHODS: The aim of this study was to examine functional hNIS expression in kidney by reverse transcription-polymerase chain reaction (RT-PCR), ribonuclease protection assay (RPA), immunohistochemistry, and Western blot analysis accompanied by iodide accumulation studies in kidney cells. RESULTS: Using a pair of full-length hNIS-specific oligonucleotide primers, RT-PCR followed by Southern hybridization revealed hNIS mRNA expression in normal human kidney tissue. The PCR products were subjected to automated sequencing and revealed full identity with the published human thyroid-derived NIS cDNA sequence. Furthermore, positive protected bands indicating the presence of hNIS mRNA were apparent in RPA gel lanes corresponding to human kidney cells as well as Chinese hamster ovary (CHO) cells stably transfected with hNIS cDNA and Graves' thyroid tissue. Immunohistochemical analysis of normal human kidney tissue using a mouse monoclonal hNIS-specific antibody showed marked hNIS-specific immunoreactivity confined to tubular cells, while no hNIS-specific immunoreactivity was detected in the glomeruli. NIS protein expression in human kidney cells was further confirmed by Western blot analysis. In addition, accumulation of (125)I was detected in human kidney cells in vitro and was shown to be sodium dependent and sensitive to perchlorate. CONCLUSIONS: Functional hNIS expression was demonstrated in the renal tubular system, suggesting that renal iodide transport may be, at least in part, an active process driven by NIS.

Anal paracoccidioidomycosis: an unusual presentation of disseminated disease.

We report a patient with an unusual anal ulceration. The biopsy of an anal lesion and subsequent studies revealed a disseminated form of paracoccidioidomycosis, observed in the lungs, small and large bowel. The anorectal disease frequently represents a secondary site of disease, and the patient must be better evaluated.

Quantitative image analysis of laser-induced choroidal neovascularization in rat.

Rodent models of laser-induced choroidal neovascularization (CNV) are now extensively used to identify angiogenic proteins, determine the role of specific genes with knockout mice, and evaluate the efficacy and safety of anti-angiogenic therapies. CNV is typically evaluated by fluorescein angiography or vascular endothelial cell labeling in histologic sections. The current study examined an alternative method using high molecular weight FITC-dextran (MW 2 x 10(6)) for high resolution angiography in RPE-choroid-sclera flat mounts. At 24 hr after lasering, the lesions appeared as a circular weakly fluorescent area of approximately equal diameter to the laser spot. No FITC-dextran labeled blood vessels were visible in the lesion at day 1. Three days after lasering, 47% of the lesions showed FITC-dextran labeling indicative of CNV. The incidence (71%) and extent of CNV increased by day 6, and by day 10 all lesions were vascularized, and the maximal area was attained. No significant change followed day 10, and the neovascular area remained constant through day 31. The highest rate of blood vessel growth (between 3 and 10 days after laser) correlates with the peak expression of VEGF, bFGF, and their receptors shown in previous studies. Morphologic analysis of flat mounts and histologic sections showed that the neovascular plexus in most lesions originates from deeper choroidal vessels in the center of the lesion, grows towards the neural retina, then branches circumferentially to anastamose with uninjured choriocapillaris. The microvessels in these lesions are broad and flat, similar to normal choriocapillaris. In a separate study, rats were treated daily with the angiostatic corticosteroid dexamethasone (20-500 microg kg(-1)day(-1)), and CNV was examined at day 10 in FITC-dextran labeled flat mounts and histologic sections. Dexamethasone dose-dependently inhibited CNV, and its highest dose inhibited approximately 95% of CNV labeled by FITC-dextran and resulted in lesions with no detectable Factor VIII immunostaining. High resolution angiography with FITC-dextran is reproducible and quantifiable, and it may accelerate the discovery of therapeutic agents that modulate choroidal neovascularization.

Thyroid nodules and cancer. When to wait and watch, when to refer.

Thyroid nodules, a common problem in clinical practice, are usually benign; only about 5% of these nodules harbor malignancy. The first step in evaluation is measurement of serum TSH levels. When the TSH value is suppressed, a hyperfunctioning nodule is likely, and scintigraphy may be helpful for confirming the diagnosis. Because thyroid cancer is extremely rare in "hot" nodules, such a finding is reassuring. Observation alone or treatment with radioiodine is a reasonable alternative to surgery in many of these patients. Fine-needle aspiration biopsy is the single most important procedure for differentiating benign from malignant thyroid nodules, and its role in evaluation and management of nodular thyroid disease cannot be overemphasized. Ultrasound, scintigraphy, and radioiodine scanning, together with measurement of various tumor markers, are useful adjuncts in the preoperative and postoperative management of patients with thyroid cancer. A carefully thought-out management plan can help reduce the risk of unnecessary surgery in these patients.

An unusual case of inappropriate secretion of thyrotropin: neoplastic or nonneoplastic?

OBJECTIVE: To report an unusual case that illustrates the difficulties in distinguishing neoplastic (nIST) from nonneoplastic inappropriate secretion of thyrotropin (nnIST). METHODS: We describe clinical, biochemical, genetic analysis, and magnetic resonance imaging (MRI) results in a patient with hyperthyroidism due to IST, and we review the related literature. RESULTS: The patient demonstrated overt clinical and biochemical hyperthyroidism with inappropriately increased thyrotropin levels, which failed to respond to thyrotropin-releasing hormone (TRH) stimulation. Sex hormone-binding globulin (SHBG) levels were in the hyperthyroid range. Alpha subunit levels were normal, as was the alpha subunit/thyrotropin molar ratio. MRI of the pituitary was negative for tumor during a 2-year period, and octreotide scan was also negative for sellar uptake. Basal oxygen consumption was abnormally increased. Genetic analysis failed to reveal mutations of the thyroid receptor b gene. The patient responded well to radioiodine ablation of his thyroid. CONCLUSION: This patient had clinical symptoms of hyperthyroidism associated with some features characteristic of nIST (increased level of SHBG, lack of thyrotropin response to TRH stimulation, absence of thyroid receptor b mutations) and others typical of nnIST (normal alpha subunit and its molar ratio to thyrotropin, absence of tumor on sellar imaging). Close follow-up with periodic MRI of the sella is important because of the possible existence of a small pituitary tumor, which may become apparent at a later date. Therapy to control symptoms is important. Hormone replacement, if needed, should be adjusted to maintain clinical euthyroidism, guided by free thyroxine levels.

Monoclonal antibodies against the human sodium iodide symporter: utility for immunocytochemistry of thyroid cancer.

The recent cloning of the thyroidal protein that is responsible for iodide transport, the sodium iodide symporter (hNIS), has made possible studies designed to characterize its structure, function and expression in thyroidal tissues. Using a mannose binding protein (MBP)-hNIS fusion protein as antigen, we have developed mouse monoclonal antibodies against hNIS to utilize as tools in such studies. Twenty-four clones were initially recovered which recognized the MBP-hNIS fusion protein, but only two of them were specific for hNIS while the others recognized MBP alone. Both antibodies were found to be immunoglobulin G (IgG) 1kappa (kappa). The specificity of antibodies was tested by Western blotting using membranes prepared from COS-7 cells transiently transfected with the pcDNA3 plasmid containing the full-length hNIS cDNA, or cells transfected with the pcDNA3 vector. A major band with a molecular weight (MW) of approximately 97 kDa, and several minor bands with MW of approximately 160 kDa, approximately 68 kDa, approximately 30 kDa and approximately 15 kDa, were detected specifically in the hNIS-transfected cells. After enzymatic deglycosylation, the major band was present at 68 kDa, as expected based upon the amino acid sequence of hNIS. Immunohistochemistry was performed with several different types of thyroid tissue and non-thyroidal tissues, using the monoclonal antibodies. Strong immunostaining was observed in Graves' tissue, with intermediate staining in papillary and follicular thyroid cancers and an absence of staining in Hürthle cell cancer. The staining was specific for the follicular epithelium and was concentrated in the basolateral portion of the cell membrane. These monoclonal hNIS antibodies should prove useful in the characterization of NIS expression in benign and malignant thyroid tissue and in studies characterizing its structure and function.

Changes in bone density after exposure to oral anticoagulants: a meta-analysis.

Oral anticoagulants are putative risk factors for osteoporosis, but observational cross-sectional studies describing their effects on bone mineral density have reported conflicting results, prospective studies are not available, and randomized trials are not feasible. To determine the association between exposure to oral anticoagulants and changes in bone density, we systematically reviewed nine original cross-sectional studies on the effect of long-term exposure to any oral anticoagulant on bone density in adults. The effect size was assessed by standardized mean difference (SMD, exposed minus unexposed) and pooled by skeletal site; results are reported in standard deviation units. Bone density was significantly decreased among exposed subjects in the ultradistal radius (SMD, -0.39; 95% CI, -0.67 to -0.10) but not in the distal radius (SMD, -0.47; 95% CI, -0.97 to 0.04), lumbar spine (SMD, -0.27; 95% CI, -0.59 to 0.05), femoral neck (SMD, 0.03; 95% CI, -0.22 to 0.29) or femoral trochanter (SMD, -0.18; 95% CI, -0.48 to 0.11). The evidence should be considered with caution, but it is consistent with a negative association of oral anticoagulants with bone density in the ultradistal radius, although not in the spine or hip. This suggests that long-term oral anticoagulation might be associated with no more than a modest increase in osteoporotic fracture risk, but this should be verified in future longitudinal studies.

Clomiphene-induced severe hypertriglyceridemia and pancreatitis.

Clomiphene has been available for clinical use since 1960 and has been successfully used to aid fertility in women with certain anovulatory disorders. It is a synthetic estrogen analog, of the triphenylethylene derivative group, and its biochemical structure is similar to that of tamoxifen. Estrogen and tamoxifen lower total and low-density lipoprotein cholesterol and increase triglyceride and high-density lipoprotein cholesterol levels. In patients with baseline hypertriglyceridemia, these agents can induce severe hypertriglyceridemia and pancreatitis. The actions of clomiphene on lipid metabolism have not been studied, and to our knowledge, no cases of severe hypertriglyceridemia related to the use of clomiphene have been described. We report the case of a woman who developed 2 episodes of clomiphene-induced hypertriglyceridemia and pancreatitis while receiving this drug for treatment of infertility. Given the striking structural similarity between clomiphene and tamoxifen, it is likely that clomiphene is capable of inducing severe hypertriglyceridemia in patients with certain underlying lipid disorders by a mechanism similar to that of tamoxifen.

Long-term use of oral anticoagulants and the risk of fracture.

BACKGROUND: Vitamin K participates in bone metabolism and, since oral anticoagulants antagonize vitamin K, their use may increase the risk of osteoporosis. OBJECTIVE: To evaluate fracture risk at all skeletal sites following exposure to oral anticoagulants. METHODS: In a population-based retrospective cohort study, 572 Olmsted County, Minnesota, women 35 years or older at their first lifetime venous thromboembolism event between 1966 and 1990 were followed up for fractures. Risk was assessed by comparing new fractures with the number expected from sex- and age-specific fracture incidence rates for the general population (standardized incidence ratio [SIR]). RESULTS: Altogether, 480 fractures occurred during 6314 person-years of follow-up. Increasing exposure to oral anticoagulation was associated with an increased SIR for vertebral fractures: at less than 3 months of exposure, 2.4 (95% confidence interval [CI], 1.6-3.4); 3 to less than 12 months, 3.6 (95% CI, 2.5-4.9); and 12 months or more, 5.3 (95% CI, 3.4-8.0); and for rib fractures: at less than 3 months, 1.6 (95% CI, 0.9-2.7); 3 to less than 12 months, 1.6 (95% CI, 0.9-2.6); and 12 months or more, 3.4 (95% CI, 1.8-5.7). The data revealed no increased risk for other types of fractures. Oral anticoagulation for 12 months or more was an independent predictor of vertebral fractures (P = .009) and rib fractures (P = .02), but not other fractures. CONCLUSIONS: Long-term exposure to oral anticoagulation is associated with an increased risk of vertebral and rib fractures. The mechanism by which this occurs is still unclear and needs further investigation.