Stress Elicits Contrasting Effects on Rac1-Cofilin Signaling in the Hippocampus and Amygdala.

There is accumulating evidence for contrasting patterns of stress-induced morphological and physiological plasticity in glutamatergic synapses of the hippocampus and amygdala. The same chronic stress that leads to the formation of dendritic spines in the basolateral amygdala (BLA) of rats, leads to a loss of spines in the hippocampus. However, the molecular underpinnings of these divergent effects of stress on dendritic spines are not well understood. Since the activity of the Rho GTPase Rac1 and the actin-depolymerizing factor cofilin are known to play a pivotal role in spine morphogenesis, we investigated if alterations in this signaling pathway reflect the differential effects of stress on spine plasticity in the hippocampus and amygdala. A day after the end of chronic immobilization stress (2 h/day for 10 days), we found a reduction in the activity of Rac1, as well as its effector p21-activated kinase 1 (PAK1), in the rat hippocampus. These changes, in turn, decreased cofilin phosphorylation alongside a reduction in the levels of profilin isoforms. In striking contrast, the same chronic stress increased Rac1, PAK1 activity, cofilin phosphorylation, and profilin levels in the BLA, which is consistent with enhanced actin polymerization leading to spinogenesis in the BLA. In the hippocampus, on the other hand, the same stress caused the opposite changes, the functional consequences of which would be actin depolymerization leading to the elimination of spines. Together, these findings reveal a role for brain-region specific differences in the dysregulation of Rac1-to-cofilin signaling in the effects of repeated stress on two brain areas that are implicated in the emotional and cognitive symptoms of stress-related psychiatric disorders.

Imbalance of flight-freeze responses and their cellular correlates in the Nlgn3-/y rat model of autism.

BACKGROUND: Mutations in the postsynaptic transmembrane protein neuroligin-3 are highly correlative with autism spectrum disorders (ASDs) and intellectual disabilities (IDs). Fear learning is well studied in models of these disorders, however differences in fear response behaviours are often overlooked. We aim to examine fear behaviour and its cellular underpinnings in a rat model of ASD/ID lacking Nlgn3. METHODS: This study uses a range of behavioural tests to understand differences in fear response behaviour in Nlgn3-/y rats. Following this, we examined the physiological underpinnings of this in neurons of the periaqueductal grey (PAG), a midbrain area involved in flight-or-freeze responses. We used whole-cell patch-clamp recordings from ex vivo PAG slices, in addition to in vivo local-field potential recordings and electrical stimulation of the PAG in wildtype and Nlgn3-/y rats. We analysed behavioural data with two- and three-way ANOVAS and electrophysiological data with generalised linear mixed modelling (GLMM). RESULTS: We observed that, unlike the wildtype, Nlgn3-/y rats are more likely to response with flight rather than freezing in threatening situations. Electrophysiological findings were in agreement with these behavioural outcomes. We found in ex vivo slices from Nlgn3-/y rats that neurons in dorsal PAG (dPAG) showed intrinsic hyperexcitability compared to wildtype. Similarly, stimulating dPAG in vivo revealed that lower magnitudes sufficed to evoke flight behaviour in Nlgn3-/y than wildtype rats, indicating the functional impact of the increased cellular excitability. LIMITATIONS: Our findings do not examine what specific cell type in the PAG is likely responsible for these phenotypes. Furthermore, we have focussed on phenotypes in young adult animals, whilst the human condition associated with NLGN3 mutations appears during the first few years of life. CONCLUSIONS: We describe altered fear responses in Nlgn3-/y rats and provide evidence that this is the result of a circuit bias that predisposes flight over freeze responses. Additionally, we demonstrate the first link between PAG dysfunction and ASD/ID. This study provides new insight into potential pathophysiologies leading to anxiety disorders and changes to fear responses in individuals with ASD.

The Readability of Patient Education Materials Pertaining to Gastrointestinal Procedures.

Introduction: Due to the ubiquity and ease of access of Internet, patients are able to access online health information more easily than ever. The American Medical Association recommends that patient education materials be targeted at or below the 6th grade level in order to accommodate a wider audience. In this study, we evaluate the difficulty of educational materials pertaining to common GI procedures; we analyze on the readability of online education materials for colonoscopy, flexible sigmoidoscopy, and esophagogastroduodenoscopy (EGD). Methods: Google search was performed using keywords of "colonoscopy," "sigmoidoscopy," and "EGD" with "patient information" at the end of each search term. The texts from a total of 18 studies, 6 for each of the procedures, were then saved. Each study was also subdivided into "Introduction," "Preparation," "Complications," and if available, "Alternatives." Furthermore, medical terminology that was properly explained, proper nouns, medication names, and other copyright text were removed in order to prevent inflation of the difficulty. Five validated readability tests were used to analyze each study and subsections: Coleman-Liau, New Dale-Chall, Flesch-Kincaid, Gunning Fog, SMOG. Results: Studies on colonoscopy, flexible sigmoidoscopy, and EGD had median readability grades of 9.7, 10.2, and 11.0, respectively. Analysis of the subsections revealed that the "Alternative" subsection was the most difficult to comprehend with a readability score of 11.4, whereas the "Introduction" subsection was the easiest to comprehend with a readability score of 9.5. Conclusion: Despite modifications to the studies that improved the readability scores, patient education materials were still significantly above the recommended 6th grade level across all websites. This study emphasizes that clear and simple language is warranted in order to create information that is suitable for most patients.

Correction of amygdalar dysfunction in a rat model of fragile X syndrome.

Fragile X syndrome (FXS), a commonly inherited form of autism and intellectual disability, is associated with emotional symptoms that implicate dysfunction of the amygdala. However, current understanding of the pathogenesis of the disease is based primarily on studies in the hippocampus and neocortex, where FXS defects have been corrected by inhibiting group I metabotropic glutamate receptors (mGluRs). Here, we observe that activation, rather than inhibition, of mGluRs in the basolateral amygdala reverses impairments in a rat model of FXS. FXS rats exhibit deficient recall of auditory conditioned fear, which is accompanied by a range of in vitro and in vivo deficits in synaptic transmission and plasticity. We find presynaptic mGluR5 in the amygdala, activation of which reverses deficient synaptic transmission and plasticity, thereby restoring normal fear learning in FXS rats. This highlights the importance of modifying the prevailing mGluR-based framework for therapeutic strategies to include circuit-specific differences in FXS pathophysiology.

Detection of unknown atrial fibrillation by prolonged ECG monitoring in an all-comer patient cohort and association with clinical and Holter variables.

OBJECTIVES: Prolonged ECG monitoring is clinically useful to detect unknown atrial fibrillation (AF) in stroke survivors. The diagnostic yield of prolonged ECG monitoring in other patient populations is less well characterised. We therefore studied the diagnostic yield of prolonged Holter ECG monitoring for AF in an unselected patient cohort referred from primary care or seen in a teaching hospital. METHODS: We analysed consecutive 7-day ECG recordings in unselected patients referred from different medical specialities and assessed AF detection rates by indication, age and comorbidities. RESULTS: Seven-day Holter ECGs (median monitoring 127.5 hours, IQR 116 to 152) were recorded in 476 patients (mean age 54.6 (SD 17.0) years, 55.9% female) without previously known AF, requested to evaluate palpitations (n=241), syncope (n=99), stroke or transient ischaemic attack (n=75), dizziness (n=29) or episodic chest pain (n=32). AF was newly detected in 42/476 (8.8%) patients. Oral anticoagulation was initiated in 40/42 (95.2%) patients with newly detected AF. Multivariate logistic regression, adjusted for age, sex and monitoring duration found four clinical parameters to be associated with newly detected AF: hypertension OR=2.54, (1.08 to 8.61) (adjusted OR (95% CI)), p=0.034; previous stroke or TIA OR=4.14 (1.81 to 13.01), p=0.001; left-sided valvular heart disease OR=5.07 (2.48 to 18.70), p<0.001 and palpitations OR=2.86, (1.33 to 10.44), p=0.015. CONCLUSIONS: Open multispeciality access to prolonged ECG monitoring, for example, as part of integrated, cross-sector AF care, can accelerate diagnosis of AF and increase adequate use of oral anticoagulation, especially in older and symptomatic patients with comorbidities.

Mesalazine-induced eosinophilic variant of Wegener's granulomatosis in an ulcerative colitis patient.

A 24-year-old woman presented with two weeks history of progressive shortness of breath associated with sharp chest pain. She had been on mesalazine for two years for Ulcerative Colitis. Chest X-ray showed bilateral pulmonary infiltrates with left sided pleural effusion. Blood investigations revealed, positive pANCA, negative cANCA and peripheral eosinophillia. Video assisted thoracoscopic lung biopsy specimen was consistent with eosinophillic variant of Wegener's granulomatosis. She responded to combination of withdrawal of mesalazine and high dose steroids. To our knowledge this is the first reported case of mesalazine induced eosinophilic variant of Wegener's granulomatosis.

Differentiated thyroid carcinoma in a juvenile patient.

Juvenile differentiated carcinoma thyroid is a rare entity. It differs from adult differentiated thyroid carcinoma in a variety of ways, including large tumor volume at presentation with early involvement of the capsule, more frequent nodal and distant metastases, greater expression of sodium-iodide symporter and early recurrence. The overall survival seems to be better than for adult patients; however, due to high and early recurrence rates, prompt and adequate treatment is advocated. The mainstay of treatment includes total thyroidectomy, central lymphadenectomy with modified radical lateral lymphadenectomy, followed by ablation with radioactive iodine (RAI). Both modalities improve the final outcome, but RAI ablation decreases cause-specific death risk independent of the extent of surgery. We present the case of a 5-year-old girl, the youngest ever treated in our country with surgery and RAI therapy successfully after being diagnosed as papillary carcinoma of the thyroid, follicular variant.

Comparative Readability Analysis of Online Patient Education Resources on Inflammatory Bowel Diseases.

BACKGROUND: The National Institutes of Health recommend a readability grade level of less than 7th grade for patient directed information. In this study, we use validated readability metrics to analyze patient information from prominent websites pertaining to ulcerative colitis and Crohn's disease. METHODS: The terms "Crohn's Disease," "Ulcerative Colitis," and "Inflammatory Bowel Disease" were queried on Google and Bing. Websites containing patient education material were saved as a text file and then modified through expungement of medical terminology that was described within the text. Modified text was then divided into subsections that were analyzed using six validated readability scales. RESULTS: None of the websites analyzed in this study achieved an estimated reading grade level below the recommended 7th grade. The median readability grade level (after modification) was 11.5 grade levels for both Crohn's disease and ulcerative colitis. The treatment subsection required the highest level of education with a median readability grade of 12th grade (range of 6.9 to 17). CONCLUSION: Readability of online patient education material from the analyzed popular websites far exceeds the recommended level of being less than 7th grade. Patient education resources should be revised to achieve wider health literacy.

Comparative analysis of online patient education material pertaining to hepatitis and its complications.

BACKGROUND AND AIMS: Approximately 50% of patients leave the doctor's office with a poor understanding of their diagnosis. Online patient education websites are becoming a major source of information for many of the patients. Here, we determine the reading grade level of online patient education materials on hepatitis B, hepatitis C, cirrhosis, and hepatocellular cancer and compare it with the National Institutes of Health-recommended reading grade level of sixth to seventh grade or under. METHODS: A Google search was performed to retrieve patient reading materials. Text was modified to remove medical terms that were defined within the article. Documents were then divided into categories of introduction, risk factors, symptoms, diagnosis, treatment, and prevention. Each document was then analyzed using six validated readability tests to determine the grade level and complexity on the basis of the number of words, syllables, or number of uncommon words. RESULTS: Modified documents had a mean readability score of 10.23, although the recommended score is less than 7.0. Cirrhosis had the highest reading grade level, with a median of 11.3, whereas hepatitis B and hepatocellular carcinoma had the easiest readability, with a median of 9.5. Furthermore, treatment subsection was the most difficult, with a median score of 10.8. CONCLUSION: Patient reading materials reviewed in this study were written well above the recommended reading grade level. These findings suggest review of patient education materials in an effort to close the gap between the average reading level and the reading materials.

CDKL5 and Shootin1 Interact and Concur in Regulating Neuronal Polarization.

In the last years, the X-linked cyclin-dependent kinase-like 5 (CDKL5) gene has been associated with epileptic encephalopathies characterized by the early onset of intractable epilepsy, severe developmental delay, autistic features, and often the development of Rett syndrome-like features. Still, the role of CDKL5 in neuronal functions is not fully understood. By way of a yeast two hybrid screening we identified the interaction of CDKL5 with shootin1, a brain specific protein acting as a determinant of axon formation during neuronal polarization. We found evidence that CDKL5 is involved, at least in part, in regulating neuronal polarization through its interaction with shootin1. Indeed, the two proteins interact in vivo and both are localized in the distal tip of outgrowing axons. By using primary hippocampal neurons as model system we find that adequate CDKL5 levels are required for axon specification. In fact, a significant number of neurons overexpressing CDKL5 is characterized by supernumerary axons, while the silencing of CDKL5 disrupts neuronal polarization. Interestingly, shootin1 phosphorylation is reduced in neurons silenced for CDKL5 suggesting that the kinase affects, directly or indirectly, the post-translational modification of shootin1. Finally, we find that the capacity of CDKL5 to generate surplus axons is attenuated in neurons with reduced shootin1 levels, in agreement with the notion that two proteins act in a common pathway. Altogether, these results point to a role of CDKL5 in the early steps of neuronal differentiation that can be explained, at least in part, by its association with shootin1.

High-Mobility Group Box-1 Modulates the Expression of Inflammatory and Angiogenic Signaling Pathways in Diabetic Retina.

PURPOSE: The expression of high-mobility group box-1 (HMGB1) is upregulated in epiretinal membranes and vitreous fluid from patients with proliferative diabetic retinopathy and in the diabetic retina. HMGB1 mediates inflammation, breakdown of the blood-retinal barrier and apoptosis in the diabetic retina. Here, we investigated inflammatory and angiogenic signaling pathways activated by HMGB1 in diabetic retina. METHODS: Human retinal microvascular endothelial cells (HRMEC) and retinas from 1-month diabetic rats and normal rats intravitreally injected with HMGB1 were studied using RT-PCR, Western blot analysis and co-immunoprecipitation. We also studied the effect of the HMGB1 inhibitor glycyrrhizin on diabetes-induced biochemical changes in the retina. RESULTS: Diabetes and intravitreal injection of HMGB1 in normal rats induced significant upregulation of the mRNA levels of the chemokine stromal cell-derived factor-1 (SDF-1/CXCL12) receptor CXCR4 and protein levels of hypoxia-inducible factor-1α, early growth response-1, tyrosine kinase 2 and the CXCL12/CXCR4 chemokine axis. Constant glycyrrhizin intake from onset of diabetes did not affect the metabolic status of the diabetic rats, but it restored these increased mediators to control values. Stimulation of HRMEC with HMGB1 and intraviteral injection of HMGB1 significantly increased the expression of vascular endothelial growth factor (VEGF) and VEGF receptor-2. Co-immunoprecipitation studies showed that diabetes increased the interaction between CXCL12 and CXCR4 and between HMGB1 and receptor for advanced glycation end products (RAGE), but not between HMGB1 and the CXCL12/CXCR4 chemokine axis. CONCLUSIONS: Our findings suggest that HMGB1 activates inflammatory and angiogenic signaling pathways in diabetic retina mediated by RAGE.

Mutual enhancement between high-mobility group box-1 and NADPH oxidase-derived reactive oxygen species mediates diabetes-induced upregulation of retinal apoptotic markers.

The expression of the proinflammatory cytokine high-mobility group box-1 (HMGB1) is upregulated in epiretinal membranes and vitreous fluid from patients with proliferative diabetic retinopathy (PDR) and in the diabetic retina. We hypothesized that a novel mechanism exists where HMGB1 and NADPH oxidase (Nox)-derived reactive oxygen species (ROS) are mutually enhanced in the diabetic retina, which may be a novel mechanism for promoting upregulation of retinal apoptotic markers induced by diabetes. Vitreous samples from 48 PDR and 34 nondiabetic patients, retinas from 1-month diabetic rats and from normal rats intravitreally injected with HMGB1 and human retinal microvascular endothelial cells (HRMEC) stimulated with HMGB1 were studied by enzyme-linked immunosorbent and spectrophotometric assays, Western blot analysis, RT-PCR, and immunofluorescence. We also studied the effect of the HMGB1 inhibitor glycyrrhizin and apocynin on diabetes-induced biochemical changes in the retinas of rats (n = 5-7 in each groups). HMGB1 and the oxidative stress marker protein carbonyl content levels in the vitreous fluid from PDR patients were significantly higher than in controls (p = 0.021; p = 0.005, respectively). There was a significant positive correlation between vitreous fluid levels of HMGB1 and the levels of protein carbonyl content (r = 0.62, p = 0.001). HMGB1 enhanced interleukin-1ß, ROS, Nox2, poly (ADP-ribose) polymerase (PARP)-1, and cleaved caspase-3 production by HRMEC. Diabetes and intravitreal injection of HMGB1 in normal rats induced significant upregulation of ROS, Nox2, PARP-1, and cleaved caspase-3 in the retina. Constant glycyrrhizin and apocynin intake from onset of diabetes did not affect the metabolic status of the diabetic rats, but restored these increased mediators to control values. The results of this study suggest that there is a mutual enhancement between HMGB1 and Nox-derived ROS in the diabetic retina, which may promote diabetes-induced upregulation of retinal apoptotic markers.

Influence of Head and Neck Position on Oropharyngeal Leak Pressure and Cuff Position with the ProSeal Laryngeal Mask Airway and the I-Gel: A Randomized Clinical Trial.

Background. This study was designed to assess and compare the effect of head and neck position on the oropharyngeal leak pressures and cuff position (employing fibreoptic view of the glottis) and ventilation scores between ProSeal LMA and the I-gel. Material and Methods. After induction of anesthesia, the supraglottic device was inserted and ventilation confirmed. The position of the head was randomly changed from neutral to flexion, extension, and lateral rotation (left). The oropharyngeal leak pressures, fibreoptic view of glottis, ventilation scores, and delivered tidal volumes and end tidal CO2 were noted in all positions. Results. In both groups compared with neutral position, oropharyngeal leak pressures were significantly higher with flexion and lower with extension but similar with rotation of head and neck. However the oropharyngeal leak pressure was significantly higher for ProSeal LMA compared with the I-gel in all positions. Peak airway pressures were significantly higher with flexion in both groups (however this did not affect ventilation), lower with extension in ProSeal group, and comparable in I-gel group but did not change significantly with rotation of head and neck in both groups. Conclusion. Effective ventilation can be done with both ProSeal LMA and I-gel with head in all the above positions. ProSeal LMA has a better margin of safety than I-gel due to better sealing pressures except in flexion where the increase in airway pressure is more with the former. Extreme precaution should be taken in flexion position in ProSeal LMA.

An audit of single stage hypospadias repair at Ayub Hospital Complex, Abbottabad.

BACKGROUND: Single-stage hypospadias repair is increasingly being performed. We report our experience at a general surgical unit. METHODS: The first one hundred repairs are included in this observational study, set up to evaluate our results. Hypospadias was graded as distal, penile shaft or peno-scrotal, with or without chordee. A single stage procedure of urethral plate elevation. excision of fibrous tissue with preputial onlay flap was used in all patients. RESULTS: First 100 operated patients are included in this study. Frequency of major complications was 33%. including fistula (17%), meatal stenosis (7%), premature tube dislodgment (3%). epidermal sloughing and persistent chordee (2% each), and retained tube and torsion penis (1% each). Fistula rate was high (17%). Success in fistula repair was low (53%). In five patients (5%) the urethral plate was transected as it was too short and fibrosed. CONCLUSIONS: Patients presented early. This procedure may successfully relieve chordee except in peno-scrotal cases. Fistula is a common complication. Early fistula repair may improve outcome. One fourth of the children had a poor cosmetic result. It was not a major concern for parents.

MeCP2 post-translational modifications: a mechanism to control its involvement in synaptic plasticity and homeostasis?

Although Rett syndrome (RTT) represents one of the most frequent forms of severe intellectual disability in females worldwide, we still have an inadequate knowledge of the many roles played by MeCP2 (whose mutations are responsible for most cases of RTT) and their relevance for RTT pathobiology. Several studies support a role of MeCP2 in the regulation of synaptic plasticity and homeostasis. At the molecular level, MeCP2 is described as a repressor capable of inhibiting gene transcription through chromatin compaction. Indeed, it interacts with several chromatin remodeling factors, such as HDAC-containing complexes and ATRX. Other studies have inferred that MeCP2 functions also as an activator; a role in regulating mRNA splicing and in modulating protein synthesis has also been proposed. Further, MeCP2 avidly binds both 5-methyl- and 5-hydroxymethyl-cytosine. Recent evidence suggests that it is the highly disorganized structure of MeCP2, together with its post-translational modifications (PTMs) that generate and regulate this functional versatility. Indeed, several reports have demonstrated that differential phosphorylation of MeCP2 is a key mechanism by which the methyl binding protein modulates its affinity for its partners, gene expression and cellular adaptations to stimuli and neuronal plasticity. As logic consequence, generation of phospho-defective Mecp2 knock-in mice has permitted associating alterations in neuronal morphology, circuit formation, and mouse behavioral phenotypes with specific phosphorylation events. MeCP2 undergoes various other PTMs, including acetylation, ubiquitination and sumoylation, whose functional roles remain largely unexplored. These results, together with the genome-wide distribution of MeCP2 and its capability to substitute histone H1, recall the complex regulation of histones and suggest the relevance of quickly gaining a deeper comprehension of MeCP2 PTMs, the respective writers and readers and the consequent functional outcomes.

The ERK1/2 Inhibitor U0126 Attenuates Diabetes-Induced Upregulation of MMP-9 and Biomarkers of Inflammation in the Retina.

This study was conducted to determine the expression of matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of metalloproteinase-1 (TIMP-1) in a time-dependent manner and the effect of extracellular-signal-regulated kinases-1/2 (ERK1/2) inhibition on the expressions of MMP-9, TIMP-1, and inflammatory biomarkers in the retinas of diabetic rats. The expression of MMP-9 was quantified by zymography, and the mRNA level of MMP-9 and TIMP-1 was quantified by RT-PCR. The expression of inducible nitric oxide synthase (iNOS), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF- α ) was examined by Western blot analysis. MMP-9 expression was significantly higher in diabetic rat retinas compared to controls at all time points.TIMP-1 expression was nonsignificantly upregulated at 1week of diabetes and was significantly downregulated at 4 and 12 weeks of diabetes. Intravitreal administration of the ERK1/2 inhibitor U0126 prior to induction of diabetes decreased ERK1/2 activation, attenuated diabetes-induced upregulation of MMP-9, iNOS, IL-6, and TNF- α and upregulated TIMP-1 expression. In MMP-9 knockout mice, diabetes had no effect on retinal iNOS expression and its level remained unchanged. These data provide evidence that ERK1/2 signaling pathway is involved in MMP-9, iNOS, IL-6, and TNF- α induction in diabetic retinas and suggest that ERK1/2 can be a novel therapeutic target in diabetic retinopathy.

Judicious use of recombinant TSH in the management of differentiated thyroid carcinoma.

OBJECTIVE: To evaluate the feasibility of using recombinant human TSH (rhTSH) in conjunction with ¹³¹I to treat patients with differentiated thyroid carcinoma. METHODS: Between July 2003 and April 2009, 14 patients [mean age, 39.1 years (range 14-71 years)], of whom seven were treated for remnant ablation and seven for irresectable or metastatic disease, received rhTSH-aided ¹³¹I therapy. None had an adequate rise in TSH. The mean ¹³¹I dosage administered was 5206.3 MBq. Baseline thyroglobulin/anti-thyroglobulin (Tg/anti-Tg) and TSH levels were documented. rhTSH (0.9 mg) was given intramuscularly on days 1 and 2, and TSH levels were recorded. ¹³¹I was given when the TSH level rose to >30 µIU/ml. Tg/anti-Tg levels were measured at 3-month intervals. A ¹³¹I whole-body scan (¹³¹I scan) was performed 6 or 12 months after treatment. RESULTS: The baseline median valid Tg and TSH levels were 76.2 ng/ml (range 14.1 to >30000) and 3.63 µIU/ml (range 1.36-11.0), respectively. The rise in TSH level was 34.8-96.9 µIU/ml after the first rhTSH injection and 33.1 to >75 µIU/ml after the second injection. The post-therapy ¹³¹I scan showed uptake at disease sites in all patients, indicating the initial empirical adequacy of treatment. Follow-up ¹³¹I scan was positive for four patients, but negative for three of these patients after subsequent therapy. Complete resolution of disease was seen in eight patients and partial resolution in four after 3 months of therapy; one had stable disease; and in one patient with progressive disease, complete resolution was achieved after repeated ¹³¹I doses with thyroxine withdrawal. After a median follow-up of 39.2 months, all patients were alive and no disease recurrence was observed. The overall response rate at 3 months was 86% and had improved to 93% at the time of this review. The final ablation rate in seven patients was 100%. Apart from notable neck swelling in four patients, which was responsive to medication, and headache in two patients, no significant short-term side-effects of therapy were seen. CONCLUSION: In our setting, the use of rhTSH-aided ¹³¹I ablation and treatment was safe and effective.