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The absorption coefficient of ultrasound and shear viscosity in binary solutions of polyacrylamide with water were studied as a function of concentration and temperature. In addition, the absorption coefficient was measured as a function of frequency. The value of α/f2 increased by twofold, at 3% concentration and 20 °C, from the water value while the shear viscosity increased by four orders of magnitude. The temperature dependence of α/f2 for the polymer solutions is similar to that of pure water. [ABSTRACT FROM AUTHOR]

Lingual thyroid is a rare congenital disorder displaying ectopic thyroid tissue at the base of the tongue. This is the most common location for ectopic thyroid tissue and is usually the only thyroid tissue present. This is a case report of a 16-year-old female who presented with nasal congestion. Fiberoptic laryngoscopy showed swelling at the base of the tongue and an ultrasound examination of the neck was without visible thyroid tissue. A 99mTc-pertechnetate scintigraphy confirmed the clinical diagnosis. As the patient was euthyroid and without symptoms active surveillance was planned.

Milk fortifiers help meet the nutritional needs of preterm infants receiving their mother's own milk (MOM) or donor human milk. We conducted a randomized clinical trial (NCT03214822) in 30 very low birth weight premature neonates comparing bovine-derived human milk fortifier (BHMF) versus human-derived fortifier (H2MF). We found that fortifier type does not affect the overall microbiome, although H2MF infants were less often colonized by an unclassified member of Clostridiales Family XI. Secondary analyses show that MOM intake is strongly associated with weight gain and microbiota composition, including Bifidobacterium, Veillonella, and Propionibacterium enrichment. Finally, we show that while oxidative stress (urinary F2-isoprostanes) is not affected by fortifier type or MOM intake, fecal calprotectin is higher in H2MF infants and lower in those consuming more MOM. Overall, the source of human milk (mother versus donor) appears more important than the type of milk fortifier (human versus bovine) in shaping preterm infant gut microbiota., Competing Interests: Declaration of interests M.B.A. has consulted for DSM Nutritional Products and serves on the Malaika Vx and Tiny Health scientific advisory boards. She has received honoraria for speaking at symposia sponsored by Medela, Prolacta Biosciences, and the Institute for Advancement of Breastfeeding and Lactation Education and has contributed without remuneration to online courses on breast milk and the infant microbiome produced by Microbiome Courses. S.V.K. is currently employed by Digbi Health (3T and AI Pvt. Ltd., India), a position taken up after concluding the research presented in this study. These entities had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the article; or decision to submit the article for publication., (Crown Copyright © 2022. Published by Elsevier Inc. All rights reserved.)

Purpose: The objective of this study was (1) to systematically review the evidence of routine post-nasal space blind biopsies and/or imaging of adults with isolated serous otitis media (SOM) of unknown cause for detection nasopharyngeal malignancy (NPM), and (2) to design a clinical management algorithm for these patients., Methods: A systematic search was conducted in the databases PubMed, Embase and Cochrane Library guided by the study question "Should adults with isolated SOM of unknown cause undergo routine biopsies of the post-nasal space and/or diagnostic imaging for detection of NPM?". All retrieved studies were reviewed and quantitatively analyzed., Results: The systematic literature search identified 552 publications accessible for title-abstract screening. This yielded 23 studies for full text assessment, of which 6 were found eligible for inclusion. All six studies dealt with nasopharyngeal blind biopsies, whereas no studies on cross-sectional imaging were identified. The derived summarized results of the included studies showed that 5.5% (31/568) of patients with isolated SOM of unknown cause were diagnosed with NPM. Of these, 6.5% (2/31) had normal nasopharyngeal endoscopy (i.e., malignancy was discovered by blind biopsies). Finally, 0.35% (2/568) of patients with isolated SOM of unknown cause diagnosed with NPM had normal nasopharyngeal endoscopy findings (i.e., nasopharyngeal endoscopy ruled-out malignancy in 99.65% of patients)., Conclusions: We found no evidence supporting routine use of blind biopsies or cross-sectional imaging in adults with isolated serous otitis media of unknown cause. We propose a pragmatic management algorithm for workup of adults with persistent secretory otitis media., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: To describe the results of utilizing a human milk-based human milk fortifier (HMHMF) as rescue therapy to meet nutritional requirements in very low birth weight and preterm infants demonstrating feeding intolerance to bovine-based human milk fortifier (BHMF) in the Canadian Neonatal Intensive Care Unit (NICU) setting., Materials and Methods: At two Level III NICUs in Winnipeg, MB, Canada, a rescue protocol was implemented to provide HMHMF for infants demonstrating intolerance to BHMF. To qualify for rescue, infants were required to experience two episodes of significant gastrointestinal (GI) symptoms associated with fortification with BHMF. A case series report was conducted retrospectively examining the success of rescue therapy, growth rates, protein, and calorie intakes before and after initiation of HMHMF in seven infants., Results: Seven infants (birth weight 723 ± 247 g, gestation 25.3 ± 3.4 weeks) were treated with rescue fortification with HMHMF. All infants were transitioned off parenteral nutrition (PN) without relapse of GI symptoms. Growth rate, protein, and calorie intakes improved with the use of HMHMF., Conclusions: Very low birth weight and preterm infants with GI intolerance to BHMF were successfully rescued with use of HMHMF. Improvements in growth were achieved without need for supplementation with PN through achievement of sufficient enteral calorie and protein intakes.

The curse of ancient Egyptian DNA was lifted by a recent study which sequenced the mitochondrial genomes (mtGenome) of 90 ancient Egyptians from the archaeological site of Abusir el-Meleq. Surprisingly, these ancient inhabitants were more closely related to those from the Near East than to contemporary Egyptians. It has been accepted that the timeless highway of the Nile River seeded Egypt with African genetic influence, well before pre-Dynastic times. Here we report on the successful recovery and analysis of the complete mtGenome from a burial recovered from a remote Romano-Christian cemetery, Kellis 2 (K2). K2 serviced the ancient municipality of Kellis, a village located in the Dakhleh Oasis in the southwest desert in Egypt. The data were obtained by high throughput sequencing (HTS) performed independently at two ancient DNA facilities (Armed Forces DNA Identification Laboratory, Dover, DE, USA and Carl R. Woese Institute for Genomic Biology, University of Illinois Urbana-Champaign, Urbana, IL, USA). These efforts produced concordant haplotypes representing a U1a1a haplogroup lineage. This result indicates that Near Eastern maternal influence previously identified at Abusir el-Meleq was also present further south, in ancient Kellis during the Romano-Christian period., Competing Interests: The opinions or assertions presented herein are the private views of the authors and should not be constructed as official or as reflecting the views of the Department of Defense, its branches, the U.S. Army Medical Research and Materiel Command, de Defense Health Agency, or the Armed Forces Medical Examiner System.

We present a rare case of a 3-year-old boy with an odontogenic myxoma (OM) involving the orbita. Including our case, only nine cases of OM have been reported to involve the eye in children.There is no gold standard for treatment of OM in children with orbital involvement. The recurrence rate of OM in children seems low, which advocates for less invasive surgery. A gentle resection of the OM was carried out. The floor and medial wall of the orbit was reconstructed immediately using a non-resorbable Medpor implant with passive adaptation. Reconstruction with a Medpor implant in children has rarely been reported in the literature. No clinical or radiological recurrence was observed 24 months after surgical removal, and the patient presented with symmetric appearance and normal vision., (2016 BMJ Publishing Group Ltd.)

This paper provides a review of the treatment technologies, which utilize natural processes or passive components in wastewater treatment. In particular, this paper primarily focuses on wetland systems and their applications in wastewater treatment (as an advanced treatment unit or decentralized system), nutrient and pollutant removal (single and multiple pollutants, and metals), and emerging pollutant removal (pharmaceuticals). A summary of studies involving the plant (vegetation) effects, wetland design and modeling, hybrid and innovative systems, storm water treatment and pathogen removal is also included.

Background: Little is known about the whole body oxidative stress burden following radioactive iodine ((131)I) therapy of thyroid diseases., Methods: We studied 17 patients with benign nodular goiter treated with (131)I therapy. The targeted thyroid dose was 50 Gy in 11 patients pretreated with 0.1 mg of recombinant human TSH (rhTSH). In 6 patients, the applied thyroid dose was 100 Gy without rhTSH prestimulation. Well-established biomarkers of oxidative stress to RNA (8-oxo-7,8-dihydroguanosine; 8-oxoGuo) and DNA (8-oxo-7,8-dihydro-2'-deoxyguanosine; 8-oxodG) were measured in freshly voided morning urine (normalized against the creatinine concentration) at baseline, and 7 and 21 days after rhTSH (not followed by (131)I), and 7 and 21 days after (131)I therapy, respectively., Results: The baseline urinary excretions of 8-oxoGuo and 8-oxodG were 2.20 ± 0.84 and 1.63 ± 0.70 nmol/mmol creatinine, respectively. We found no significant changes in the excretion of any of the metabolites, neither after rhTSH stimulation alone nor after (131)I therapy. Also, no significant differences were found between the rhTSH group (low dose, median (131)I: 152 MBq) and the non-rhTSH group (high dose, median (131)I: 419 MBq; 8-oxoGuo: p = 0.66, 8-oxodG: p = 0.71)., Conclusion: Systemic oxidative stress, as detected by nucleic acids metabolites in the urine, is not increased after thyroid stimulation with 0.1 mg of rhTSH, or after (131)I therapy. Our method cannot quantify the oxidative stress induced locally in the thyroid gland, but the study supports that (131)I therapy of benign nodular goiter carries no or only a minute risk of developing subsequent malignancies. It remains to be explored whether our findings also apply to hyperthyroid disorders.

Buschke-Ollendorff syndrome is a rare condition characterized by skin manifestations and osteopoikilosis. We describe a mother and her son who presented with indurated skin lesions suggestive of connective tissue naevi. X-rays showed multiple symmetrical foci of osteosclerosis. They had both been diagnosed earlier with Calvé-Legg-Perthes disease, which on revision most likely represented Buschke-Ollendorff syndrome. Buschke-Ollendorff syndrome may imitate Calvé-Legg-Perthes disease. Skin signs may be the clue to diagnosis. Main differentials are sclerotic bone metastases and osteoma.

For treatment of benign nodular goitre the choice usually stands between surgery and (131)I therapy. (131)I therapy, used for 30 years for this condition, leads to a goitre volume reduction of 35-50% within 1-2 years. However, this treatment has limited efficacy if the thyroid (131)I uptake is low or if the goitre is large. Recombinant human TSH (rhTSH)-stimulated (131)I therapy significantly improves goitre reduction, as compared with conventional (131)I therapy without pre-stimulation, and adverse effects are few with rhTSH doses of 0.1 mg or lower. RhTSH-stimulated (131)I therapy reduces the need for additional therapy due to insufficient goitre reduction, but the price is a higher rate of hypothyroidism. Another approach with rhTSH-stimulation is to reduce the administered (131)I activity by a factor that equals the increase in the thyroid (131)I uptake. Using this approach, radiation exposure is considerably reduced while the goitre reduction is similar to that obtained with conventional (131)I therapy., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Background: Enhanced reduction of multinodular goiter (MNG) can be achieved by stimulation with recombinant human thyrotropin (rhTSH) before radioiodine ((131)I) therapy. The objective was to compare the long-term efficacy and safety of two low doses of modified release rhTSH (MRrhTSH) in combination with (131)I therapy., Methods: In this phase II, single-blinded, placebo-controlled study, 95 patients (57.2 ± 9.6 years old, 85% women, 83% Caucasians) with MNG (median size 96.0 mL; range 31.9-242.2 mL) were randomized to receive placebo (n=32), 0.01 mg MRrhTSH (n=30), or 0.03 mg MRrhTSH (n=33) 24 hours before a calculated (131)I activity. Thyroid volume (TV) and smallest cross-sectional area of trachea (SCAT) were measured (by computed tomography scan) at baseline, six months, and 36 months. Thyroid function and quality of life (QoL) was evaluated at three-month and yearly intervals respectively., Results: At six months, TV reduction was enhanced in the 0.03 mg MRrhTSH group (32.9% vs. 23.1% in the placebo group; p=0.03) but not in the 0.01 mg MRrhTSH group. At 36 months, the mean percent TV reduction from baseline was 44 ± 12.7% (SD) in the placebo group, 41 ± 21.0% in the 0.01 mg MRrhTSH group, and 53 ± 18.6% in the 0.03 mg MRrhTSH group, with no statistically significant differences among the groups, p=0.105. In the 0.03 mg MRrhTSH group, the subset of patients with basal (131)I uptake <20% had a 24% greater TV reduction at 36 months than the corresponding subset of patients in the placebo group (p=0.01). At 36 months, the largest relative increase in SCAT was observed in the 0.03 mg MRrhTSH group (13.4 ± 23.2%), but this was not statistically different from the increases observed in the placebo or the 0.01 mg MRrhTSH group (p=0.15). Goiter-related symptoms were reduced and QoL improved, without any enhanced benefit from using MRrhTSH. At three years, the prevalence of permanent hypothyroidism was 13%, 33%, and 45% in the placebo, 0.01 mg, and 0.03 mg MRrhTSH groups respectively. The overall safety profile of the study was favorable., Conclusions: When used as adjuvant to (131)I, enhanced MNG reduction could not be demonstrated with MRrhTSH doses ≤ 0.03 mg, indicating that the lower threshold for efficacy is around this level.

A three-year-old boy presented with a painless mass in the nasolabial fold and ipsilateral increased tearing. A diagnosis of odontogenic myxoma (OM) was established by biopsy, and the tumour was excised using a combined oral and transconjuctival approach. In small children OM occurs almost exclusively in the maxilla. Orbital involvement is very rare, and to our knowledge reconstruction with a Medpore sheet has not previously been reported. At post-operative follow-up normal eye function and an excellent cosmetic result was observed. OM should be considered in a midfacial mass.

Introduction: (99m)Tc-pertechnetate scintigraphy is much used in the evaluation of patients with nodular goitre. We investigated the ability of experienced observers to estimate the thyroid 24-h (131)I uptake (RAIU) and the thyroid volume by visual evaluation of the scintigram., Material and Methods: Two endocrinologists and two nuclear medicine specialists visually evaluated thyroid scintigrams from 171 patients with nodular goitre. The variables were assessed in a blinded fashion according to predefined categories and then compared with the true values. The assessments were repeated after four weeks. Kappa (κ ω) statistics were used., Results: There was a low probability (range 6-22%) for the observers to assess the thyroid RAIU correctly. The probability of assessing the thyroid volume correctly was in the 14-22% range. Endocrinologists tended to underestimate the thyroid RAIU, mostly in patients with a RAIU > 30%. All observers significantly underestimated the thyroid volume if this was > 80 ml. There was a low interobserver agreement for the thyroid RAIU assessment (κ ω-values: 0.03-0.43) as well as for the thyroid volume assessment (κ ω-values: 0.19-0.48). The corresponding κ ω-values for the intraobserver agreement were 0.34-0.68 and 0.37-0.62, respectively. Nuclear medicine specialists achieved a significantly higher agreement than endocrinologists in their evaluation of both thyroid parameters., Conclusion: Thyroid (99m)Tc scintigraphy has poor interobserver agreement and is inaccurate for assessment of quantitative thyroid parameters, even when performed by experienced specialists., Funding: This study was supported by grants from the Danish Agency for Science, Technology and Innovation., Trial Registration: not relevant.

The wave of next-generation sequencing data has arrived. However, many questions still remain about how to best analyze sequence data, particularly the contribution of rare genetic variants to human disease. Numerous statistical methods have been proposed to aggregate association signals across multiple rare variant sites in an effort to increase statistical power; however, the precise relation between the tests is often not well understood. We present a geometric representation for rare variant data in which rare allele counts in case and control samples are treated as vectors in Euclidean space. The geometric framework facilitates a rigorous classification of existing rare variant tests into two broad categories: tests for a difference in the lengths of the case and control vectors, and joint tests for a difference in either the lengths or angles of the two vectors. We demonstrate that genetic architecture of a trait, including the number and frequency of risk alleles, directly relates to the behavior of the length and joint tests. Hence, the geometric framework allows prediction of which tests will perform best under different disease models. Furthermore, the structure of the geometric framework immediately suggests additional classes and types of rare variant tests. We consider two general classes of tests which show robustness to noncausal and protective variants. The geometric framework introduces a novel and unique method to assess current rare variant methodology and provides guidelines for both applied and theoretical researchers., (© 2013 Wiley Periodicals, Inc.)

Genotyping errors are well-known to impact the power and type I error rate in single marker tests of association. Genotyping errors that happen according to the same process in cases and controls are known as non-differential genotyping errors, whereas genotyping errors that occur with different processes in the cases and controls are known as differential genotype errors. For single marker tests, non-differential genotyping errors reduce power, while differential genotyping errors increase the type I error rate. However, little is known about the behavior of the new generation of rare variant tests of association in the presence of genotyping errors. In this manuscript we use a comprehensive simulation study to explore the effects of numerous factors on the type I error rate of rare variant tests of association in the presence of differential genotyping error. We find that increased sample size, decreased minor allele frequency, and an increased number of single nucleotide variants (SNVs) included in the test all increase the type I error rate in the presence of differential genotyping errors. We also find that the greater the relative difference in case-control genotyping error rates the larger the type I error rate. Lastly, as is the case for single marker tests, genotyping errors classifying the common homozygote as the heterozygote inflate the type I error rate significantly more than errors classifying the heterozygote as the common homozygote. In general, our findings are in line with results from single marker tests. To ensure that type I error inflation does not occur when analyzing next-generation sequencing data careful consideration of study design (e.g. use of randomization), caution in meta-analysis and using publicly available controls, and the use of standard quality control metrics is critical.

Objective: The objective of the study was to evaluate the long-term outcome of recombinant human TSH (rhTSH)-augmented radioiodine ((131)I) therapy for benign multinodular nontoxic goiter., Patients and Methods: Between 2002 and 2005, 86 patients with a multinodular nontoxic goiter were treated with (131)I in two randomized, double-blind, placebo-controlled trials. (131)I-therapy was preceded by 0.3 mg rhTSH (n = 42) or placebo (n = 44). In 2009, 80 patients completed a follow-up (FU) visit, including determination of thyroid volume, thyroid function, and patient satisfaction by a visual analog scale., Results: In both groups, thyroid volume was further reduced from 1 yr to final FU (71 months). The mean goiter volume reductions obtained at 1 yr and final FU [59.2 ± 2.4% (sem) and 69.7 ± 3.1%, respectively] in the rhTSH group were significantly greater than those obtained in the (131)I-alone group (43.2 ± 3.7 and 56.2 ± 3.6%, respectively, P = 0.001 and P = 0.006), corresponding to a gain of 24% at final FU. At last FU the mean reduction in compression visual analog scale score was significantly greater in patients receiving rhTSH (P = 0.049). Additional therapy (thyroid surgery or (131)I) was required more often in the placebo group (nine of 44) compared with the rhTSH group (two of 42) (P = 0.05). The prevalence of hypothyroidism at 1 yr [9 and 43% in the placebo and rhTSH groups, respectively (P < 0.0001)] increased to 16 and 52%, respectively, at final FU (P = 0.001)., Conclusion: Enhanced goiter volume reduction with rhTSH-augmented (131)I therapy improves the long-term reduction in goiter-related symptoms and reduces the need for additional therapy compared with plain (131)I therapy. Overall patient satisfaction is benefited, despite a higher rate of permanent hypothyroidism.

The optimal treatment strategy in a goiter patient depends--among other factors--on goiter size, the degree of cosmetic or compressive symptoms, the age of the patient, the impact on the upper airways, the wish to maintain normal thyroid function, the ability of the thyroid gland to take up (131)I, and the possibility of thyroid malignancy. When treatment is warranted in a patient with benign goiter, the choice usually stands between surgery and (131)I-therapy. Focal destructive treatment, by ethanol sclerotherapy or interstitial laser photocoagulation, may be considered in patients with a solitary benign nodule. If thyroid hyperfunction due to nodular autonomy is the dominant problem, life-long anti-thyroid drug treatment may be relevant in elderly individuals. With the advent of recombinant human TSH (rhTSH) stimulation the goiter reduction following (131)I-therapy is significantly enhanced and this treatment is of particular benefit, as compared with conventional (131)I-therapy, in patients with a low baseline thyroid (131)I uptake and a large goiter. If the rhTSH dose does not exceed 0.1 mg the risk of temporary hyperthyroidism and acute thyroid swelling is low. Since patient satisfaction seemingly is not improved by the greater goiter reduction obtained by rhTSH-stimulated (131)I-therapy, and permanent hypothyroidism is more frequent, it may be more relevant to reduce the administered radioactivity equivalent to the rhTSH-induced increase in the thyroid (131)I uptake. Future large-scale well-controlled studies should explore this strategy, with focus on cost-benefit and quality of life. A major hindrance of widespread and routine use of rhTSH-stimulated (131)I-therapy is its present status as an off-label treatment.

The present study was conducted to determine the efficacy of novel flavonoid vicenin-2 (VCN-2), an active constituent of the medicinal herb Ocimum Sanctum Linn or Tulsi, as a single agent and in combination with docetaxel (DTL) in carcinoma of prostate (CaP). VCN-2 effectively induced anti-proliferative, anti-angiogenic and pro-apoptotic effect in CaP cells (PC-3, DU-145 and LNCaP) irrespective of their androgen responsiveness or p53 status. VCN-2 inhibited EGFR/Akt/mTOR/p70S6K pathway along with decreasing c-Myc, cyclin D1, cyclin B1, CDK4, PCNA and hTERT in vitro. VCN-2 reached a level of 2.6±0.3μmol/l in serum after oral administration in mice which reflected that VCN-2 is orally absorbed. The i.v. administration of docetaxel (DTL), current drug of choice in androgen-independent CaP, is associated with dose-limiting toxicities like febrile neutropenia which has lead to characterization of alternate routes of administration and potential combinatorial regimens. In this regard, VCN-2 in combination with DTL synergistically inhibited the growth of prostate tumors in vivo with a greater decrease in the levels of AR, pIGF1R, pAkt, PCNA, cyclin D1, Ki67, CD31, and increase in E-cadherin. VCN-2 has been investigated for radioprotection and anti-inflammatory properties. This is the first study on the anti-cancer effects of VCN-2. In conclusion, our investigations collectively provide strong evidence that VCN-2 is effective against CaP progression along with indicating that VCN-2 and DTL co-administration is more effective than either of the single agents in androgen-independent prostate cancer., (Copyright © 2011 Elsevier Inc. All rights reserved.)

A 78 year-old woman with life-threatening angiotensin-converting enzyme inhibitor (ACE-i) induced angioedema was unresponsive to conventional treatment with corticosteroids, antihistamines and epinephrine. She was successfully treated with icatibant licensed for treatment of hereditary angioedema knowing that both conditions involve bradykinin induced activation of bradykinin B2 receptors. Randomised, controlled trials are warranted to document the efficacy of icatibant in ACE-i angioedema.

Context and Objective: Stimulation with recombinant human TSH (rhTSH) before radioiodine (131I) therapy augments goiter volume reduction (GVR). Observations indicate that rhTSH has a preconditioning effect beyond increasing thyroid (131)I uptake. We test the hypothesis that an equivalent GVR might be obtained by an absorbed thyroid dose well below what has been used previously., Patients and Design: In a double-blinded setup, 90 patients (78 women; median age, 52 yr; range, 22-83) with a nontoxic nodular goiter (median size, 63 ml; range, 25-379 ml) were randomized to either 0.1 mg rhTSH (n=60) followed by a thyroid dose of 50 Gy or placebo followed by 100 Gy (n=30)., Results: At 12 months, the mean relative GVR in the placebo and the rhTSH group was identical (35+/-3%; P=0.81). The median administered 131I-activity was 170 MBq (45-1269) in the rhTSH group and 559 MBq (245-3530) in the placebo group (70% reduction, P<0.0001). According to the official radiation regulation, hospitalization was required in 14 patients in the placebo group vs. one patient in the rhTSH group (P<0.0001). In both groups, goiter-related symptoms were effectively relieved in the majority of patients. The prevalence of myxedema (10%) did not differ among groups., Conclusions: This is the first study to demonstrate that rhTSH not only increases the thyroid 131I uptake, but per se potentiates the effect of 131I-therapy, allowing a major reduction of the 131I-activity without compromising efficacy. This approach is attractive in terms of minimizing posttherapeutic restrictions and in reducing the potential risk of radiation-induced malignancy.

Context: Recombinant human TSH (rhTSH) is used to augment the effect of radioiodine therapy for nontoxic multinodular goitre. Reports of acute thyroid swelling and hyperthyroidism warrant safety studies evaluating whether these side-effects are dose dependent., Objective: To determine the effects on thyroid size and function of various doses of rhTSH., Design: In nine healthy male volunteers, the effect of placebo, 0.1, 0.3 and 0.9 mg of rhTSH was examined in a paired design including four consecutive study rounds., Main Outcome Measures: Main outcome measures were evaluated at baseline, 24 h, 48 h, 96 h, 7 days and 28 days after rhTSH and included: Thyroid volume (TV) estimation by planimetric ultrasound, and thyroid function by serum TSH, free T3, free T4 and Tg levels., Results: Following placebo or 0.1 mg rhTSH, the TV did not change significantly from baseline at any time. At 24 and 48 h after administration of 0.3 mg rhTSH, the TV increased by 37.4 +/- 12.3% (SEM) (P = 0.03) and 45.3 +/- 16.1% (P = 0.05) respectively. After 0.9 mg rhTSH, the TV increased by 23.3 +/- 5.8% (P = 0.008) and 35.5 +/- 18.4% (P = 0.02) respectively. The increase in serum FT3, FT4 and thyroglobulin (Tg) was greater when administering 0.3 mg compared with 0.1 mg (P = 0.02) and when administering 0.9 mg compared with 0.3 mg (P = 0.02). After 0.1 mg rhTSH, the increase in FT3 and Tg was not significantly different from placebo whereas the FT4 increase was significantly higher (P = 0.02 compared with placebo)., Conclusions: In healthy individuals, rhTSH-induced thyroid swelling and hyperthyroidism is rapid and dose dependent. If valid for patients with goitre, our results suggest that these adverse effects are unlikely to be of clinical significance, following doses of rhTSH of 0.1 mg or less.