Utility of computed tomography in identifying an ectopic thyroid in infants and pre-school children

In purpose of identifying thyroid tissue in patients with congenital hypothyroidism during childhood, ultrasonography is usually used as a screening examination, and scintigraphy is performed secondarily. Though these methods are useful, it is not easy to identify the accurate location of thyroid tissue by these methods. We previously reported the utility of computed tomography (CT) in identifying thyroid tissue in four cases of congenital hypothyroidism. The purpose of this study is to investigate whether CT is useful in identifying thyroid tissue, compared to ultrasonography or scintigraphy. Nineteen cases (0 month to 18 years of age) that were suspected to have ectopic thyroid tissue or thyroid agenesis on ultrasonography were examined by CT. CT was useful in diagnosing ectopic thyroid tissue or thyroid agenesis in all the cases, whereas ultrasonography or scintigraphy was less accurate in this purpose in seven cases. Plain CT had a difficulty in identifying thyroid tissue in two cases, in which contrasted image was required. This study showed that CT, especially an enhanced CT, is useful in identifying thyroid tissue, when the gland is not identified in the normal position by ultrasonography.     

Extremely early onset of ranitidine action on human histamine H2 receptors expressed in HEK293 cells

BACKGROUND/AIMS: Histamine H2 receptor antagonists are considered to exert their effects on gastric acid secretion more rapidly than proton pump antagonists. However, there are no reports concerning the direct interaction of a histamine H2 receptor antagonist with the human H2 receptor in terms of onset of action. This study aims to characterize how rapidly famotidine and ranitidine, the most widely used histamine H2 receptor antagonists, interact with the human histamine H2 receptor. METHODS: HEK293 cell lines, stably expressing human histamine H2 receptors, were obtained. The dose- and time-dependent effects of famotidine and ranitidine on [3H]-tiotidine binding and histamine-stimulated cAMP production were analyzed. RESULTS: Ranitidine inhibited both [3H]-tiotidine binding and histamine-stimulated cAMP production more promptly than did famotidine. Inhibition of histamine-stimulated cAMP production by Cmax doses of famotidine (20 mg p.o.) and ranitidine (150 mg p.o.) peaked by 15 and 2 min, respectively. [3H]-tiotidine binding was not saturated by 60 min at the famotidine Cmax, while the ranitidine Cmax had produced saturation by 15 min. CONCLUSION: Ranitidine inhibits the human histamine H2 receptor very rapidly.     

A pseudohypoparathyroidism type Ia patient with normocalcemia

Pseudohypoparathyroidism type Ia (PHP-Ia), one of 4 types of PHP, is a genetic disease characterized by clinical hypoparathyroidism caused by parathyroid hormone (PTH) resistance. In addition, patients with PHP-Ia show resistance to other hormones as well as Albright's hereditary osteodystrophy (AHO), a constellation of features including short stature, obesity, brachydactyly, ectopic ossifications, and/or mental retardation. Hypocalcemia is one of the hallmarks of PHP-Ia, but several PHP-Ia patients have been described to have normocalcemia. We encountered a 10-year-old girl with typical Albright's hereditary osteodystrophy with round face, short stature, brachydactyly, and obesity. Biochemical examination showed normocalcemia and increased PTH levels. Ellsworth-Howard test did not show any responses of urinary cAMP and phosphate. Based on these findings, she was diagnosed as having PHP-Ia with normocalcemia. Sequencing analysis of the GNAS gene identified a heterozygous missense mutation in exon 13 (R385H), which was previously reported in a PHP-Ia patient. The exact reason for her normocalcemia is not determined, but we must recognize heterogeneous biochemical findings even in PHP-Ia.     

Free-to-total leptin ratio in maternal plasma is constant throughout human pregnancy

To clarify the mechanism of leptin resistance during pregnancy, we measured plasma leptin concentrations, free to total leptin ratio (percent free leptin) and soluble leptin receptor concentrations in pregnant women, and compared the results with those in non-pregnant women. We collected plasma samples from 23 non-pregnant and 31 pregnant women in the third trimester. Plasma samples from 5 pregnant women were collected longitudinally in each trimester. Plasma leptin concentrations in pregnant women in the second trimester (17.4 +/- 3.2 ng/ml) were higher than those in the first trimester of pregnancy (11.0 +/- 2.8 ng/ml, n = 5), as previously reported. However, percent free leptin did not change significantly throughout pregnancy. Percent free leptin correlated with total leptin concentrations (ng/ml) in non-pregnant women (r = 0.727, P < 0.0001), but not in women in the third trimester of pregnancy (r = 0.006). Constant percent free leptin during pregnancy despite increased leptin concentrations indicates increased leptin binding capacity in pregnant women, that might partly contribute to the establishment of leptin resistance. On the other hand, soluble leptin receptor concentrations showed significant negative correlation with BMI and plasma leptin concentrations in pregnant women (r = -0.470, P < 0.01 and r = -0.493, P < 0.01, respectively) but not in non-pregnant women. These data suggest the possibility that soluble leptin receptor is a minor component of leptin binding capacity in the plasma of pregnant women.     

Acute retrobulbar optic neuritis with anti-myelin oligodendrocyte glycoprotein antibody-associated disease complicated with microscopic polyangiitis: A case report

Rationale:Anti-myelin oligodendrocyte protein antibody-associated disease (MOGAD) is a new disease entity with various clinical phenotypes. MOGAD often present with recurrent optic neuritis (ON), and it can also develop as a compartment of neuromyelitis optica spectrum disorder (NMOSD). Moreover, multiple autoantibodies such as an anti-myeloperoxidase antineutrophil cytoplasmic antibody (MPO-ANCA) had been reported in the serum of patients with NMOSD.Patient concerns:We report an 86-year-old woman with a 2-year history of microscopic polyangiitis (MPA). The patient had a rapid loss of vision in her left eye. No abnormal findings were observed on her left fundus, and she tested negative for MPO-ANCA upon admission. However, anti-MOG antibodies were observed in the patient''s serum and cerebrospinal fluid.Diagnosis:A diagnosis of MOGAD complicated with MPA was made.Interventions:The patient received twice steroid pulse therapy and oral azathioprine as maintenance therapy.Outcomes:Her vision rapidly recovered, and no subsequent relapse was observed during the 8-month observation period.Conclusion:To the best of our knowledge, this is the first case of MOGAD complicated with MPA, and steroid pulse therapy and azathioprine therapy were effective for ON caused by MOGAD.     

Isolation of measles virus from middle ear fluid of infants with acute otitis media

Measles virus was isolated from the middle ear fluid (MEF) of two infant cases of acute otitis media (AOM) associated with measles. This is the first report on the isolation of measles virus from the MEF in patients with AOM, and possibility of the measles virus as a causative agent of AOM was suggested.     

C-terminal Src kinase (CSK) modulates insulin-like growth factor-I signaling through Src in 3T3-L1 differentiation

IGF-I stimulates both proliferation and differentiation of adipocyte-precursor cells, preadipocytes in vivo and in vitro. We have previously shown that IGF-I stimulates proliferation of 3T3-L1 preadipocytes through activation of MAPK and MAPK activation by IGF-I is mediated through the Src family of nonreceptor tyrosine kinases. In addition, we have shown that when 3T3-L1 cells reach growth arrest and are stimulated to differentiate, IGF-I can no longer activate the MAPK pathway. We hypothesized that the loss of IGF-I signaling to MAPK in differentiating 3T3-L1 cells is due to loss of IGF-I activation of Src family kinases. We measured c-Src kinase activity in cell lysates from proliferating, growth-arrested and differentiating 3T3-L1 cells. Src activity increased 2- to 4-fold in IGF-I-stimulated proliferating cells; however, IGF-I had a marginal affect on Src activity in growth-arrested cells and inhibited Src activity localized at the membrane in differentiating cells. C-terminal Src kinase (CSK), a ubiquitously expressed nonreceptor tyrosine kinase, negatively regulates the Src family kinases by phosphorylation of the Src C-terminal tyrosine. IGF-I decreased phosphorylation of the Src C-terminal tyrosine in proliferating cells and increased phosphorylation of this site in differentiating cells. IGF-I stimulated CSK kinase activity 2-fold in differentiating 3T3-L1 cells. An association between CSK and c-Src was detected by immunoprecipitation following IGF-I stimulation of differentiating but not proliferating 3T3-L1 cells. These results suggest that the loss of IGF-I downstream mitogenic signaling in differentiating 3T3-L1 cells is due to a change in IGF-I activation of c-Src and CSK may mediate the inactivation of c-Src by IGF-I in 3T3-L1 adipogenesis.     

Involvement of central metastin in the regulation of preovulatory luteinizing hormone surge and estrous cyclicity in female rats

Ovulation is caused by a sequence of neuroendocrine events: GnRH and LH surges that are induced by positive feedback action of estrogen secreted by the mature ovarian follicles. The central mechanism of positive feedback action of estrogen on GnRH/LH secretion, however, is not fully understood yet. The present study examined whether metastin, the product of metastasis suppressor gene KiSS-1, is a central neuropeptide regulating GnRH/LH surge and then estrous cyclicity in the female rat. Metastin had a profound stimulation on LH secretion by acting on the preoptic area (POA), where most GnRH neurons projecting to the median eminence are located, because injection of metastin into the third ventricle or POA increased plasma LH concentrations in estrogen-primed ovariectomized rats. Metastin neurons were immunohistochemically found in the arcuate nucleus (ARC) to be colocalized with estrogen receptors with some fibers in the preoptic area (POA) in close apposition with GnRH neuronal cell bodies or fibers. Quantitative RT-PCR has revealed that KiSS-1 and GPR54 mRNAs were expressed in the ARC and POA, respectively. The blockade of local metastin action in the POA with a specific monoclonal antibody to rat metastin completely abolished proestrous LH surge and inhibited estrous cyclicity. Metastin-immunoreactive cell bodies in the ARC showed a marked increase and c-Fos expression in the early proestrus afternoon compared with the day of diestrus. Thus, metastin released in the POA is involved in inducing the preovulatory LH surge and regulating estrous cyclicity.     

Relationship between dominant prolongation of the filtered QRS duration in the right precordial leads and clinical characteristics in Brugada syndrome

Background: Electrical abnormalities in the RVOT may be involved in Brugada syndrome.
Objectives: We investigated the relationship between the signal-averaged ECG (SAECG) and electrophysiologic study (EPS), especially focusing on conduction delay in the outflow tract of the right ventricle (RVOT) and its contribution to clinical characteristics.
Methods: Twenty-four patients with Brugada syndrome (23 men and 1 woman; 61 ± 16 years old) were studied. We assessed the presence of late potential (LP) in SAECG and the filtered QRS duration in the right precordial leads (V₁ or V₂; RfQRS) and in the left precordial leads (V₅ or V₆; LfQRS) and the difference between them. In 18 patients, SAECG was evaluated for an LP on three separate occasions.
Results: SAECG was positive for LP in 15 patients at least once; and in 7 patients, SAECG was positive for an LP on multiple occasions, and 6 of 7 patients (86%) had a history of cardiac arrest. The difference between RfQRS and LfQRS was significantly greater in patients with cardiac arrest than in patients with syncope or in asymptomatic patients; 29 ± 10, 14 ± 11 (P < 0.01), and 7 ± 5 msec (P < 0.001), respectively. All patients were alive and one patient with cardiac arrest had an appropriate VF therapy delivered by the ICD.
Conclusions: The dominant prolongation of the filtered QRS duration in the right precordial leads may be related to the risk of arrhythmic event in Brugada syndrome.