Event-related Potential Measures of Visual Word Processing in Monolingual and Bilingual Children and Adults: A Focus on Word Frequency Effects.

How does language background influence the neural correlates of visual word recognition in children? To address this question, we used an ERP lexical decision task to examine first-language (L1) and second-language (L2) visual word processing in monolingual and bilingual school-aged children and young adults (n = 123). In particular, we focused on the effects of word frequency (an index of lexical accessibility) on RTs and the N400 ERP component. Behaviorally, we found larger L1 versus L2 word frequency effects among bilingual children, driven by faster and more accurate responses to higher-frequency words (no other language or age group differences were observed). Neurophysiologically, we found larger L1 word frequency effects in bilinguals versus monolinguals (across both age groups), reflected in more negative ERP amplitudes to lower-frequency words. However, the bilingual groups processed L1 and L2 words similarly, despite lower levels of subjective and objective L2 proficiency. Taken together, our findings suggest that divided L1 experience (but not L2 experience) influences the neural correlates of visual word recognition across childhood and adulthood.

Enterocolitis in a Child With Hirschsprung Disease.

Hirschsprung disease is a congenital abnormality that can be surgically corrected. However, Hirschsprung-associated enterocolitis can be a life-threatening sequela. Very little has been published in the emergency medicine literature about the risk of enterocolitis and shock in patients with a history of Hirschsprung disease. We describe the case of a 6-month-old male infant with a history of multiple surgeries for Hirschsprung disease who presented to the emergency department with a seemingly benign viral gastrointestinal illness. His stable condition led him to be discharged. However, 4 days later, he returned to the emergency department with severe diarrhea and was subsequently admitted to the pediatric intensive care unit for the management of enterocolitis and shock. With this case report, we aim to raise emergency physicians' awareness of the serious and possibly fatal complications of Hirschsprung disease. We argue that this single element of a patient's medical history can alter the management of seemingly simple viral gastrointestinal illnesses; rather than be discharged, such a patient requires surgical consultation and possibly admission for close monitoring and treatment.

Synthesis and antiviral properties of spirocyclic [1,2,3]-triazolooxazine nucleosides.

An efficient synthesis of spirocyclic triazolooxazine nucleosides is described. This was achieved by the conversion of ß-D-psicofuranose to the corresponding azido-derivative, followed by alkylation of the primary alcohol with a range of propargyl bromides, obtained by Sonogashira chemistry. The products of these reactions underwent 1,3-dipolar addition smoothly to generate the protected spirocyclic adducts. These were easily deprotected to give the corresponding ribose nucleosides. The library of compounds obtained was investigated for its antiviral activity using MHV (mouse hepatitis virus) as a model wherein derivative 3 f showed the most promising activity and tolerability.

Gender Differences in CDC Guideline Compliance for STIs in Emergency Departments.

INTRODUCTION: Sexually transmitted infections (STIs) are a common reason for emergency department (ED) visits. The objective of this study was to determine if there were gender differences in adherence to Centers for Disease Control and Prevention (CDC) STI diagnosis and treatment guidelines, as documented by emergency providers. METHODS: We performed a retrospective chart review to identify patients treated for urethritis, cervicitis, and pelvic inflammatory disease (PID) in the EDs of three hospitals in a Pennsylvania network during a calendar year. Cases were reviewed to assess for compliance with CDC guidelines. We used descriptive statistics to assess the distributions of study variables by patient sex. In the analysis we used Student's t-tests, chi-square tests, and logistic regression. Statistical significance was set at p ≤ 0.05. RESULTS: We identified 286 patient records. Of these, we excluded 39 for the following reasons: incorrect disease coding; the patient was admitted and treated as an inpatient for his/her disease; or the patient left the ED after refusing care. Of the 247 participants, 159 (64.4%) were female. Females were significantly younger (26.6 years, SD=8.0) than males (31.2, SD=11.5%), (95% confidence interval [CI] [2.0- 7.0], p=0.0003). All of the males (n=88) in the cohort presented with urethritis; 25.8% of females presented with cervicitis, and 74.2% with PID. Physician compliance for the five CDC criteria ranged from 68.8% for patient history to 93.5% for patient diagnostic testing, including urine pregnancy and gonorrhea/chlamydia cultures. We observed significant differences by patient sex. Fifty-four percent of the charts had symptoms recorded for female patients that were consistent with CDC characteristics for diagnostic criteria compared to over 95% for males, OR=16.9; 95% CI [5.9-48.4], p<0.001. Similar results were observed for patient discharge instructions, with physicians completely documenting delivery of discharge instructions to 51.6% of females compared to 97.7% of complete documentation in males, OR=42.3; 95% CI [10.0-178.6] p<0.001). We observed no significant sex differences in physician documentation for physical exam or for therapeutic antibiotic treatment. CONCLUSION: This retrospective study found patient gender differences in how emergency providers complied with documenting with regard to the 2010 CDC guidelines for the diagnosis and treatment of urethritis, cervicitis, and PID. Specifically medical records of men were more likely to have complete documentation of symptoms recorded (95% CI 5.9-48.4) and to have discharge instruction documentation (95% CI 10.0-178.6) than records of women.

The effect of insulin on vascular reactivity to norepinephrine.

The effect of insulin on the vasoconstrictor response to norepinephrine of the resistance bed of the isolated perfused rat tail has been studied. Insulin produced a significant attenuation of this response in concentrations of both 120 mU./ml. and 150 micronU./ml. It is suggested that this effect may be relevant to the hypotensive action of insulin observed in diabetics.

Effects of chronic treatment of intact and hypophysectomized rats with thyroid-stimulating hormone on the metabolism of [35S]methimazole and [35S]propylthiouracil.

Chronic treatment of intact rats with various doses of TSH increased the thyroidal 35S accumulation after single doses of [35S]methimazole (MMI) and [35S]propylthiouracil (PTU). However, no effect on the intrathyroidal breakdown of the drugs was observed. Thus absolute thyroidal levels of unmetabolized MMI and PTU were increased by factors of up to 2 and 3, respectively, compared to the control groups. Simultaneous decreases in the levels of thyroidal total iodine were observed. Hypophysectomized rats showed a marked inhibition of both thyroidal accumulation and oxidation of [35S]-MMI but TSH treatment of hypophysectomized rats restored the accumulation and oxidation to sham-operated and control group levels. The results show that in rats TSH has an important role in the control of thyroidal levels of antithyroid drugs currently used in the treatment of hyperthyroidism.

Effect of frequency of administration on the accumulation and metabolism of (35S) propylthiouracil by the rat thyroid.

Repeated administration (every 8 h) of (35S) Propylthiouracil (PTU) resulted in gradual accumulation of unmetabolised PTU by the thyroid gland until the 9th dose was given. Subsequently a plateau-level was attained which was proportional to dose with the two dose levels used. During repeated administration once daily the intrathyroid concentration of free PTU varied markedly in the course of each 24-h period. Chromatographic analysis showed four compounds: PTU, sulphate and two unidentified compounds as well as origin material. The proportions of these compounds were different in the different dose studies. Thus, the ratio of compound Y/compound X was found to be inversely related to dose. The plasma 35S-radioactivity increased throughout the studies and was proportional to dose.

Relation between thyroid iodine content and the accumulation and oxidation of [35-S] Methimazole in the rat.

The thyroid accumulation and oxidation of a single intraperitoneal dose of [35-S] methimazole has been studied in iodine-deficient, normal and iodine-treated rats. A highly significant positive linear correlation was found between the thyroid oxidation of methimazole to sulfate and intrathyroidal iodine content. A single dose of potassium iodide given intraperitoneally (ip) to rats 1 h before administration of [35-S] methimazole (1 mg/kg ip) increased the thyroid accumulation and oxidation of methimazole. Conversely, the thyroids of rats maintained on a low iodine diet for 21 days showed a markedly reduced capacity to accumulate and oxidize methimazole. The level of oxidation found in the iodine-deficient, normal and iodide-treated groups was 0.21, 4.15 and 12.6 nmol sulfate/g thyroid respectively. The animals maintained on the low iodine diet for 21 days showed significant increases in thyroid weight and thus the decrease in methimazole oxidation occurred in spite of increased stimulation by endogenous TSH. These results show that the intrathyroidal iodine content is a critical factor in the metabolism of methimazole in the thyroid.

Role of TSH in the changes in thyroidal metabolism of [35S]methimazole in phenobarbital and thyroxine-treated rats.

The effect of phenobarbital (PB) and/or thyroxine on the thyroidal accumulation and oxidation of [35S]methimazole (MMI) and serum TSH levels was studied in rats. PB treatment increased the accumulation of MMI and the serum TSH levels, but concurrent administration of T4 reversed these effects. It was concluded that increased TSH secretion in PB-treated animals was likely to be the major mechanism involved in the increased MMI accumulation. PB also increased the intrathyroidal oxidation of MMI to sulphate. However, in contrast to the PB effect on accumulation, concurrent T4 administration only partially reversed the effect on oxidation. The results suggested that the increased oxidation of MMI in PB-treated animals was due to a direct effect of PB or possibly a combination of this direct effect and the indirect TSH effect. Possible mechanisms postulated for a direct effect were thyroidal microsomal enzyme induction and/or changes in thyroidal protein binding of MMI.

A prospective randomized trial of antithyroid drug dose in Graves' disease therapy. European Multicenter Study Group on Antithyroid Drug Treatment.

Some studies have suggested that increasing the daily dose of anti-thyroid drugs might improve long-term remission rates of Graves' disease. Therefore, this question was addressed in a prospective multicenter trial involving 18 thyroid clinics in Europe, mostly in iodine-deficient or moderately iodine-sufficient regions. Five hundred and nine patients with Graves' hyperthyroidism were enrolled in a prospective randomized trial comparing the remission rates after treatment with methimazole (MMI) at two fixed dosages (10 vs. 40 mg) with levothyroxine supplementation. The treatment and follow-up periods lasted 12 months each. Sixty and seven-tenths percent of the recruited patients (total, 309; 153 in the 10 mg, 156 in the 40 mg group) were finally evaluated, and comparison of the two groups showed that they were well matched with respect to a wide range of variables, including parameters of thyroid function. With 10 mg MMI daily, 68.4% of the patients were euthyroid after 3 weeks, and 84.9% after 6 weeks, compared to 83.1% and 91.6%, respectively, with the use of 40 mg MMI daily. TSH receptor antibodies decreased similarly in the two groups, 25% of patients in the 10 mg group, and 30% in the 40 mg group still being TSH receptor antibodies positive after 12 months. One hundred and ninety six (63.4%) of the 309 patients achieved remission of Graves' disease. The two MMI doses were equally effective; 35.9% compared to 37.2% of patients treated with 10 and 40 mg MMI, respectively, had relapses. There was no difference in the length of the time interval between stopping treatment and recurrence between the two groups. However, the rate of adverse drug reactions increased from 39/251 (15.5%) in the 10 mg group to 67/258 (26.0%) in the 40 mg group (P < 0.01). Under conditions of iodine deficiency or borderline sufficient iodine supply, 40 mg MMI daily will render more patients with Graves' disease euthyroid within the first 6 weeks of treatment than 10 mg daily, but at the expense of an increased rate of adverse reactions. However, patients treated with 40 mg MMI daily for 1 yr have no higher chance of remission than patients treated with 10 mg. It does not appear justified at present to recommend MMI doses higher than required for the control of hyperthyroidism (with the goal of immunosuppression).

The placental transfer of propylthiouracil, methimazole and carbimazole.

The placental transfer of 35S-labelled methimazole (MMI), carbimazole and propylthiouracil (PTU) has been examined in the rat in late pregnancy and in patients undergoing therapeutic abortion. Although rapid equilibrium of fetal and maternal serum radioactivity (FS:MS ratio 1:1) occurred after iv administration of 35S-carbimazole or 35S-MMI in rats, a persistent fetal to maternal ratio of less than one was observed after 35S-PTU administration. Results from human studies after a single oral dose indicate that, as in the rat, the placenta appeared to be more permeable to 35S-MMI than to 35S-PTU as shown by the marked difference in fetal serum:maternal serum ratios and amounts accumulated in the fetus. Localization of radioactivity in the human fetal thyroid was also observed after administration of 35S-labelled MMI, carbimazole or PTU.

Thyroid function in patients in clinical remission after medical treatment of thyrotoxicosis.

This paper described the changes in the levels of serum triiodothyronine, serum thyroxine,serum thyrotrophin and other indices of thyroid function between 2-5 y after completion of antithyroid drug therapy in 35 patients who were euthyroid on clinical criteria. There was a small but significant elevation of the mean triiodothyronine and thyroxine levels with a relative hypersecretion of Triiodothyronine. No correlation was found between the levels of either thyroid hormone measured or their ratio and the radioiodine uptakes and clearance rate, the plasma inorganic iodine level, the absolute iodine uptake or the serum TSH level. There was no case of clinical hypothyroidism but in one patient the TSH level was at the upper limit of the nrmal range and an exaggerated TSH response to TRH was found.

Inhibition of NK cell-induced cytolysis by thiocarbamide antithyroid drugs.

The thiocarbamide antithyroid drugs, methimazole and propylthiouracil, suppressed natural killer (NK) cell-induced cytolysis in vitro (determined by the release of 51Cr-chromate from labelled target cells) in a dose-dependent manner. Parallel experiments demonstrated a similar reduction in NK cell luminol chemiluminescence during activation by K562 tumour cells. It would appear, therefore, that an association may exist between NK cell-induced cytolysis and the peroxidase/oxygenase activity of these lymphocytes.

Influence of sodium perchlorate on thiourylene antithyroid drug accumulation in mice.

Radiolabelled [35S]propylthiouracil and [35S]methimazole were shown to accumulate in mouse thyroid gland in vivo, with maximal tissue/plasma ratios and maximal intrathyroidal levels of 35S-labelled drug being seen at the lowest dose of drug studied (0.1 micrograms/animal). Pretreatment with sodium perchlorate (10 mg) abolished iodide trapping by the thyroid and caused a fall in accumulation of both [35S]methimazole and [35S]propylthiouracil, although this effect was not seen at higher doses of drug, when tissue/plasma ratios approached unity. These data suggest that thiourylene antithyroid drug accumulation by the thyroid gland does not depend directly on the anion trap, and it is suggested that this accumulation might depend on subsequent intrathyroidal drug metabolism.

Accumulation of thiourylene antithyroid drugs in mouse salivary gland.

[35S]Methimazole and [35S]propylthiouracil were shown to accumulate in mouse submandibular gland in vivo, with maximal tissue: plasma ratios being achieved at the lowest dose of drug studied (0.1 microgram/animal). Autoradiography of submandibular glands showed that the drugs were localized to the intralobular ductal epithelium and within the lumen of the convoluted granular tubule, which was identical to the localization of radiolabelled iodide. Histochemical studies indicated that this was the site of peroxidase activity within the gland. Drug accumulation persisted when iodide trapping was competitively inhibited using perchlorate. These data suggest that antithyroid drug accumulation by this tissue is not dependent on the anion trap; the localization of drug and iodide at the site of peroxidase activity suggest that this may be an important factor in the mechanism of drug accumulation, possibly related to subsequent drug metabolism.

Peroxidase activity in relation to iodide, 17 beta-oestradiol and thioureylene drug uptake in human polymorphoneutrophils.

In polymorphoneutrophils (PMNs) phagocytosis is accompanied by an increase in peroxidase activity. Accumulation of iodide, thioureylene antithyroid drugs and 17 beta-oestradiol also occurs during the process. There is no evidence of an active iodide transport system in the PMNs as pertechnetate is not concentrated and neither ouabain nor perchlorate abolishes iodide accumulation. The uptakes of 125I, [35S]PTU and [3H]-17 beta-oestradiol were compared in phagocytosing PMNs and the effects of various compounds examined. In addition, chemiluminescence generation from luminol by PMNs and by horseradish peroxidase was studied. This indicated that uptake of all three compounds could be associated with activation of the peroxidase system, and inhibition of this enzyme system caused a reduction in their accumulation.

Transient hypothyroidism following radioiodine therapy for thyrotoxicosis.

A prospective study of thyroid function including serial tracer radioisotope uptake measurements in 55 patients treated with 131I therapy is described. Five patients had an episode of transient hypothyroidism within eight months of treatment: in three of these patients this was due to impaired organification of iodide, with normal iodide trapping by the thyroid (as measured by a twenty minute 123I uptake) being preserved. In contrast, in all patients who developed permanent hypothyroidism, iodide trapping was markedly diminished and did not recover. It is suggested that hypothyroidism due to organification failure following 131I therapy is potentially short-lived; where hypothyroidism is associated with gross impairment of iodide trapping, recovery is unlikely. Early iodine uptake measurements may be of value in selecting those patients whose hypothyroidism is transient and who do not require permanent thyroid hormone replacement.

Radiological protection guidance for radioactive patients--new data for therapeutic 131I.

Patients leaving hospital after 131I treatment for thyrotoxicosis face restrictions on their contact with other members of the public. These restrictions depend on the level of residual body radioactivity which for practical purposes can be taken to be almost entirely in the thyroid gland. This study provides an appropriate data base from which to draw advice to patients consistent with current radiological protection requirements in terms of the duration of these restrictions. Thyroidal retention of 131I was measured in 77 thyrotoxic patients over a period of 1-50 days after a first therapeutic administration of the radionuclide. Mean 131I activity in the gland (+/- S.D.) at 1 day was 56.1 +/- 11.1% of the administered dose activity and thereafter retention followed a single exponential decay pattern with a mean effective half-life (+/- S.E.M.) of 6.35 +/- 0.14 days. In patients who required further 131I therapy, there was evidence that retention could be markedly reduced if there was virtual ablation of thyroid tissue. It is proposed that these retention data can be used to determine body radioactivity at any interval after the administration of 131I for treatment of thyrotoxicosis, thus obviating the need for serial measurements in every individual patient.

Emergency presentation of an elderly female patient with profound hypoglycaemia.

We present the case of an elderly non-diabetic female who was admitted to hospital as an emergency due to loss of consciousness. Her clinical presentation was consistent with hypoglycaemia due to a massive insulin overdose. However, the patient refuted the possibility of insulin administration, and the circumstances were reported to the police for investigation. This case demonstrates the clinical and biochemical characteristics of insulin overdose. Furthermore, it serves to illustrate the sequence of events that may be created when foul play is suspected, and the factors related to patient confidentiality that require consideration by the responsible physician.

Erectile dysfunction in patients with diabetes.

Erectile dysfunction, which is common among men with diabetes, leads to significant reduction in quality of life, and as with other complications of diabetes deserves to be treated on the NHS. This article explores the problem of erectile dysfunction and diabetes and the role of sildenafil, which is likely to be the first choice treatment of patients presenting with erectile dysfunction.