A somatic mutation in the thyrotropin receptor gene in a patient with an autonomous nodule within a multinodular goiter

Thyrotropin (TSH) is the prime regulator of thyroid cell growth and function and acts through the thyrotropin receptor (TSHR) located on the surface membrane of thyrocytes. Somatic heterozygous mutations that cause TSHR activation in the absence of TSH have been found in toxic adenomas and in hot nodules of multinodular goiters. Clinically and histologically heterogeneous nodules can share common gain-of-function mutations. Mutation prevalence varies greatly and is inversely related to iodine intake of the population. We report a Greek patient presenting with subclinical hyperthyroidism due to a fast-growing autonomous hyperplastic nodule in a long-standing multinodular goiter. Direct DNA sequencing showed that the hot nodule harbored a somatic heterozygous activating TSHR mutation: substitution of glutamine for leucine in the third transmembrane helix. This mutation (L512Q) was recently described in two solitary toxic adenomas. This report expands the spectrum of mutations shared by dissimilar hot nodules, supporting a common mechanism for nonautoimmune thyroid autonomy. The identification of the L512Q substitution demonstrates that gain-of-function TSHR mutations are encountered in Greece, although iodine deficiency has been significantly corrected over the last three decades.     

The analgesic effect of gabapentin and mexiletine after breast surgery for cancer

We investigated the analgesic efficacy of mexiletine and gabapentin on acute and chronic pain associated with cancer breast surgery in 75 patients. They were randomized to receive, in a double-blinded manner, mexiletine 600 mg/d, gabapentin 1200 mg/d, or placebo for 10 days. Anesthesia was standardized, and all patients had access to routine postoperative analgesics on demand. The visual analog scale score assessed pain at rest and after movement. Three months later, all patients were interviewed to identify intensity of chronic pain and analgesic requirements. Mexiletine and gabapentin reduced codeine consumed from the second to tenth day by 50% (P = 0.029; P = 0.018 and P = 0.035 for mexiletine versus control and gabapentin versus control comparisons, respectively). Total paracetamol consumption was also reduced during the same time (P = 0.0085; P = 0.007 and P = 0.011 for the mexiletine and gabapentin groups when compared with the control, respectively). Pain at rest and after movement was reduced by both drugs on the third postoperative day. Pain after movement also was reduced by gabapentin between the second and fifth postoperative day. Three months later, the incidence of chronic pain, its intensity, and need for analgesics were not affected by either treatment. However, burning pain was more frequent in the control group (P = 0.033). IMPLICATIONS: Patients undergoing breast surgery for cancer may develop chronic pain. We evaluated the effect of mexiletine and gabapentin on the acute and chronic pain after breast surgery for cancer. Both drugs reduced the postoperative analgesic requirements, and particularly, gabapentin reduced pain after movement. The overall incidence of chronic pain was unaffected except for burning pain.     

Self-citations in six anaesthesia journals and their significance in determining the impact factor

Self-citation of a journal may affect its impact factor. We investigated self-citations in the 1995 and 1996 issues of six anaesthesia journals by calculating the self-citing and self-cited rates for each journal. Self-citing rate relates a journal's self- citations to its total number of references. We defined self-cited rate as the ratio of a journal's self-citations to the number of times it is cited by the six anaesthesia journals. We also correlated self-citing rates with the impact factor of the six journals for 1997. Citations among the six journals differed significantly (P < 0.0001). Anesthesiology had the highest self-citing rate (57%). Anaesthesia, Anesthesia and Analgesia, British Journal of Anaesthesia, Canadian Journal of Anaesthesia and the European Journal of Anaesthesiology had self-citing rates of 28%, 28%, 30%, 11% and 4% respectively. The self- cited rates were 31%, 35%, 34%, 27%, 31% and 17% for Anaesthesia, Anesthesiology, Anesthesia and Analgesia, British Journal of Anaesthesia, Canadian Journal of Anaesthesia and the European Journal of Anaesthesiology, respectively. North America journals cited the North America literature. This also occurred, to a lesser extent, in the European anaesthesia journals. A significant correlation between self-citing rates and impact factors was found (r = 0.899, P = 0.015). A high self-citing rate of a journal may positively affect its impact factor.      

The antiemetic effect of droperidol: is it dose dependent?

One hundred and thirty patients scheduled for ENT surgery were randomly allocated to one of the four groups: 3 to 5 minutes before anesthesia the first group (n = 19) received 5 mg of droperidol I.V., the second group (n = 30) 2.5 mg, the third group (n = 32) 0.5 mg and the fourth group (n = 49) received 2 ml of normal saline. Normal saline or droperidol were administered in a double blind manner from 2 ml coded ampules. The postanesthetic incidence of vomiting in the control group was 59% and was found to be significantly higher when compared with the droperidol treated groups (chi2 = 19.5228, P less than 0.0005). The incidence of vomiting in the groups treated with high, moderate or low dose of droperidol varied between 16 and 21% and did not differ significantly between them (chi2 = 0.26035, P greater than 0.80).     

Piracetam attenuates the changes in the surface potential of the phosphatidylcholine monolayer produced by alcohols

The surface potential changes produced by three alcohols on the phosphatidylcholine (PC) monolayer, either alone or in combination with piracetam were studied. The PC monolayer was formedon 145 mM KCL in a teflon trough and the surface change was measured by means of a Kiethley electrometer, with the high impedence output connected to an Americium 241 air electrode and the low impedence output to a calomel reference electrode. The alcohols produced a negative going change in the surface charge of the monolayer, proportional to the chain length of carbon atoms and amount of alcohol added. 10 microliter (2 mg) of piracetam applied to the PC monolayer before adding the alcohols partially inhibited the changes produced by them. It seems that in vitro piracetam opposes the action of alcohols on this membrane model.     

Early to bed: a study of adaptation among sexually active urban adolescent girls younger than age sixteen

OBJECTIVE: To examine the association between sexual activity among urban adolescent girls and four global measures of psychosocial adaptation (academic motivation, school achievement, depressive symptoms, and expectations about the future). METHOD: Data derived from the Social and Health Assessment, a self-report survey administered in 1998 to students in the public school system in New Haven, CT (149 classes at 17 middle and high schools). RESULTS: Of 1,413 respondents (57% black, 28% Hispanic; mean age 13.4 +/- 1.7 years), 414 (29%) acknowledged prior sexual intercourse; the proportions of sexually active girls in 6th, 8th, and 10th grades were 14%, 30%, and 50%, respectively. In multivariate analyses of covariance, sexual activity was significantly associated with all four measures of psychosocial adaptation (p < .001). Other correlates of at least one measure of maladaptation included socioeconomic status, sensation seeking, and lower school grade (p < .001 for each), peer pressure (p < .01), and black ethnicity, and the interaction of sexual activity by lower school grade (p < .05 for each). CONCLUSIONS: Compared with their sexually naive peers, sexually active adolescent girls had lower scores on global measures of psychosocial adaptation. These findings have clinical, policy, and research relevance to a vulnerable population at high risk of teenage pregnancy and sexually transmitted diseases.     

Stereological estimation of total intracranial volume on CT images

This study aims to investigate the possibility of generating stereological estimations of total intracranial volume (TIV) on CT scans. The study group included 16 consecutive patients referred for a cranial CT examination. The TIV was estimated using the stereological point counting technique. Volume measurements were optimized by systematically sampling CT sections and by defining an optimum spacing between test points of the grid. The intraobserver and interobserver variability of the optimized volumetric technique was determined. Stereological TIV estimations were compared with the respective planimetric measurements. The application of a test grid with a point spacing of 2.4 cm on 6–8 systematically sampled CT sections provided TIV estimations with a coefficient of error of less than 5%. The intraobserver and interobserver coefficient of variation values were found to be 2.4 and 4.0%, respectively. The 95% limits of agreement between stereological and planimetric TIV measurements were equal to –91.4 and 103.4 cm³. The mean time (±SD) needed to obtain stereological TIV estimations was 2.9±0.6 min. The application of the optimized stereological technique on CT scans enables the efficient estimation of TIV.     

Relevance of the restoration of humeral length and retroversion in hemiarthroplasty for humeral head fractures

Sixteen patients, with a fracture of the upper humerus treated with hemiarthroplasty, were followed-up for 45.7 +/- 15.1 (20-72) months after surgery. The results were assessed using the Constant-Murley scale. The mean score was 75.8 +/- 15.7 (54-96) points out of a possible maximum of 100. At the time of their last follow-up they underwent CT of the fractured and contralateral humerus. Humeral length and retroversion were measured and evaluated. A very good final outcome (Constant score more than 71) was achieved in patients with a difference in retroversion less than 10 degrees and a difference in length less than 14 mm, between fractured and sound humerus. The mean difference in retroversion was 8.7 degrees and the mean difference in length was 0.65 cm, between fractured and sound humerus. We attribute the very good clinical outcome in our series to the quality of the anatomical reconstruction that was performed.     

Is chronic ethanol consumption associated with tolerance to intrathecal lidocaine in the rat?

Intoxication with alcohols can produce anesthesia. In contrast, chronic ethanol consumption can produce tolerance to inhaled and other general anesthetics. We tested whether ongoing consumption decreased, and whether withdrawal from such consumption increased, the intrathecal dose of lidocaine that induces sensory and motor blockade in female Sprague-Dawley rats. Sensory blockade was assessed using the tail-flick test, and motor blockade by the animal's inability to move its hind limbs. Rats were tested before commencing ethanol intake; during ethanol ingestion (9 days after beginning ingestion); and on the 15th day of ingestion, 14 h after withdrawing ethanol from their diet. Pair-fed control rats were tested at the same intervals. Ongoing administration of ethanol decreased the dose of lidocaine required to produce sensory blockade, but this difference was not significant relative to the control group (i.e., the difference was significant within group but not across groups). Withdrawal of ethanol increased the dose requirements for sensory and motor blockade by 80% and 53% (P less than 0.01 and P less than 0.0001) and decreased the duration of the motor blockade (P less than 0.01). Dose requirements producing sensory block differed between alcoholic and control groups (P less than 0.0001). These results suggest that chronic ethanol intake produces tolerance to the local anesthetic effects of lidocaine. Whether this change results from a change in kinetics or in sensitivity is not known, but the latter would seem more likely, because duration of blockade was minimally affected or unaffected.     

The proteasome inhibitor bortezomib drastically affects inflammation and bone disease in adjuvant‐induced arthritis in rats

Objective

To explore the effect of bortezomib in splenocytes and fibroblast‐like synoviocytes (FLS) and its in vivo potency in a rat model of adjuvant‐induced arthritis (AIA), which resembles human rheumatoid arthritis (RA).

Methods

AIA was induced with Freund's complete adjuvant. Splenocyte and FLS proliferation and apoptosis were measured by radioactivity incorporation and flow cytometry, respectively. The invasiveness of FLS from rats with AIA was tested in a Transwell system. The pattern of cytokine secretion was evaluated by cytometric bead array in splenocyte supernatants. Bortezomib was administered prophylactically or therapeutically, and arthritis was assessed clinically and histologically. Immunohistochemistry was performed for markers of inflammation and angiogenesis in joints. Hematologic and biochemical parameters were tested in peripheral blood (PB). Representative animals were examined by computed tomography (CT) scanning before and after bortezomib administration. The expression of Toll‐like receptor 2 (TLR‐2), TLR‐3, and TLR‐4 in PB and FLS was measured by real‐time polymerase chain reaction, and alterations in specific cell populations in PB and spleen were determined by flow cytometry.

Results

In vitro, bortezomib exhibited significant inhibitory and proapoptotic activity in splenocytes and FLS from rats with AIA, altered the inflammatory cytokine pattern, and reduced the invasiveness of FLS from rats with AIA. In vivo, bortezomib significantly ameliorated disease severity. Remission was associated with improved histology and decreased expression of CD3, CD79a, CD11b, cyclooxygenase 1, and factor VIII in target tissues as well as down‐regulation of TLR expression in PB and cultured FLS. CT scanning demonstrated a bone healing effect after treatment.

Conclusion

Our findings suggest that bortezomib affects AIA in a pleiotropic manner and that this drug may be effective in RA.