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Background The exact differences between the TU wave complex of ATS1 and that of healthy individuals remain to be investigated. We sought to characterize the TU wave complex of Andersen–Tawil syndrome type 1 (ATS1) using high frequency electrocardiogram (ECG) data. Methods Electrocardiograms were recorded as time series data with a 2 kHz frequency ECG amplifier in 13 patients with ATS1 (positive for KCNJ2 mutation, ATS1 group) and age‐matched healthy individuals (control group). Conventional ECG parameters were measured, and principal component analysis (PCA) and independent component analysis (ICA) were applied to the TU wave complex. Results Time from T peak (Tp) to U peak (Up), time from bottom (B) to Up, and time from B to U end (BUe, U duration) (0.232 ± 0.018 vs. 0.165 ± 0.017, p

Background— The main ECG criteria for the diagnosis of long-QT syndrome (LQTS) include abnormal T-wave morphology as well as prolonged QT interval. The T wave in LQTS probably includes additional components of the myocardial repolarization process, which are derived from aberrant ion currents. We investigated whether independent component analysis (ICA) can extract such abnormal repolarization components. Methods and Results— Digital ECG data were obtained as a time series from 10 channels using 20 surface electrodes in 22 patients with genetically confirmed LQTS type 1 (LQT1) and 30 normal subjects. In each case, T-wave area was analyzed by radical ICA after noise reduction by the wavelet thresholding method. Furthermore, inverse ICA was applied to determine the origin of each independent component (IC). Radical ICA revealed that a T-wave consisted of 4 basic ICs in all control subjects, whereas ≥5 (mostly 6) ICs were identified in all 22 patients with LQT1. The extra ICs, which were not evident in normal subjects, were assumed to contribute to the formation of abnormal T-wave morphology. The extra ICs were identified even in patients with normal QTc values and in those taking β-blockers. Inverse ICA indicated that the additional ICs originate predominantly from the late phase of the T wave of the left ventricle. Conclusions— Extra ICs appear during repolarization in all patients with LQT1 but not in normal subjects. ICA is a potentially useful multivariate statistical method to differentiate patients with LQT1 from normal subjects.

Long QT syndrome is a high-risk condition associated with arrhythmia due to its sudden cause of death. Prenatal diagnosis of long QT syndrome, however, is impossible using the fetal echocardiogram. Here we present the first reported case of long QT syndrome in which a prenatal diagnosis was made using non-invasive fetal electrocardiogram. We consider that the non-invasive fetal electrocardiogram may be a good method for diagnosing fetal QT prolongation.

Our aim was to demonstrate a digital analyzing method that could extract the potential of early excitation derived from accessory conductive pathway (ACP) from fusion of the QRS complex wave of the electrocardiogram of Wolf-Parkinson-White (WPW) syndrome. A 13-year-old boy with WPW syndrome received successful catheter ablation therapy. ECG was recorded and analyzed using independent component analysis (ICA) and inverse independent component analysis (I-ICA), at pretherapy and posttherapy. We identified the ACP potential and the following potential spread to the ventricle. Results agreed with those of intracardiac mapping, locating the ACP in the left posterior side of the heart. ICA and I-ICA might be useful for noninvasive analysis of WPW syndrome ECG and other electrocardiac abnormalities.

We report an autopsy study of late-onset familial amyloid polyneuropathy with a variant transthyretin Val30Met in 2 brothers living in Kyoto, Japan. The disease onsets were at 64 and 59 years, and they died at 71 and 74 years old, respectively. They exhibited almost the same postmortem findings. Amyloid deposition was remarkable in the hearts, but was not seen in the renal glomeruli. In the peripheral nervous system, amyloid deposition was most prominent in the nerves immediately caudal to ganglia, moderate in the dorsal and sympathetic ganglia, and mild in the spinal roots, sciatic nerves, and distal nerves. The difference between the amyloid deposition in the proximal portion and distal portion of the extremity nerves appeared to be greater in the late-onset type than in the ordinary type, and this proximal deposition of amyloid may have induced severe distal nerve fiber degeneration.

A 38-year-old Japanese male who had traveled in China from September 13 to October 5, 1997, developed fever and severe conjunctivitis from October 20. After he was hospitalized in Kyoto City Hospital for persistent high fever on October 29, he developed muscular weakness and dysphagia which continued for two weeks. An electromyogram showed a myogenic pattern, and laboratory findings showed significant elevation of serum enzyme levels of muscle origin: CPK, 3,095 IU/l; aldorase, 195 IU/l; myoglobin, 7,570 ng/ml, and myoglobinuria, 94,700 ng/ml. The WBC was 10,800/microliter with 45% eosinophils. Muscular biopsy showed degeneration of muscle fibers with infiltration of macrophages and lymphocytes. On further inquiry, it was revealed that the patient had eaten smoked bear meat in China on September 30, three weeks prior to the onset of symptoms. A dot-ELISA serologic test for parasites was positive for Trichinella. Further, a coiled 1.2 mm long Trichinella larve was recovered from approximately 100 mg of frozen biopsied muscle by an enzyme digestion method. Mebendazole was given to the patient at a dosage of 200 mg/day for seven days. CPK levels were normalized within 3 days of the beginning of the treatment, and he was discharged without any symptoms. Physicians must be aware of trichinellosis and should include it in their differential diagnosis when examining patients with myositis and eosinophilia of unknown origin.

We detected and isolated human metapneumovirus (HMPV) and isolated another respiratory virus in pharyngeal swab specimens from 502 pediatric patients with acute respiratory infection, seen at 3 Kyoto City sentinel hospitals from January to December 2011. Our prospective study detected 43 positive HMPV cases (8.6%). Phylogenetic analysis showed that subgroup A2 was most common, followed by B1 and B2, and that A1 was not detected. HMPV was detected mostly in specimens from patients less than 3 years old, and positive HMPV was identified most in spring, peaking in March. Our clinical study showed that positive HMPV patients had fever above 38 degrees (86%) and cough (65%). Among the 30 whose chest radiography was examined, radiological findings were recognized in 18 cases. We found inflammatory infiltrative shadows around the bronchus and peribronchus near the hilum of the lung. Lobar pneumonia and diffuse infiltrative shadows coinciding with peripheral alveolar involvement were not recognized. No difference affecting illness severity was seen among subgroups, viral isolation results, or mixed coxsackie virus or influenza virus infection. In hospitalization, mean disease lasted significantly longer in those with lower respiratory tract symptoms at first'examination than in those without such symptoms. We detected HMPV RNA in pharyngeal swabs and stool specimens from patients admitted to the hospital for rhabdomyolysis.

Intrathecal administration of thyrotropin-releasing hormone (TRH) resulted in an increase in plasma epinephrine (E) and glucose levels in conscious rats. To elucidate the mechanisms by which TRH stimulates the release of E, the animals were pretreated with 5,7-dihydroxytryptamine, parachlorophenylalanine, methysergide or ketanserin. Serotoninergic denervation suppressed the TRH-induced increase in plasma E and glucose levels, whereas inhibition of serotonin (5-HT) synthesis or blockade of 5-HT receptors did not suppress the responses. These findings suggest that the serotoninergic neurons, but not 5-HT itself, are involved in stimulating the sympathetic outflow by TRH at the spinal level.

Intracerebroventricular administration of SMS 201-995 (5 micrograms/rat), a somatostatin analogue, induced barrel rotation in rats. Pretreatment with ceruletide (40 micrograms/100 g b. wt., IP) 3 days or 7 days prior to the injection of SMS 201-995 significantly inhibited the response rate of barrel rotation induced by SMS 201-995, but not that induced by arginine-vasopressin (1 microgram/rat, ICV). The suppressive effect of ceruletide on barrel rotation could be partially countered by MK-329, a selective peripheral CCK (CCK-A) receptor antagonist. Desulfated cerulein did not affect the barrel rotation induced by SMS 201-995. These findings suggest that ceruletide specifically suppresses the barrel rotation evoked by SMS 201-995 in a long-lasting manner possibly acting through CCK-A receptor.

Effects of intrathecal (i.t.) administration of TRH and the TRH analogue, DN1417, on plasma catecholamines and glucose levels were studied in conscious male rats. The i.t. administration of TRH (0.6 and 3 nmol) at the T8–10 vertebral level resulted in a dose-related increase in epinephrine (E), norepinephrine (NE), and glucose levels, which was suppressed by prior administration of the ganglionic blocker, hexamethonium (1.5 mg/100 g b. wt.). I.t. administration of TRH (3 nmol) caused small increases in plasma E and glucose at the C7-T1 vertebral level, but it did not change plasma E, NE and glucose levels at the sacral level. DN1417 (3 nmol) administered i.t. at the T8–10 or C7-T1 vertebral level had a more potent and long-lasting effect in stimulating the release of E than TRH. These findings suggest that TRH may act on sympathetic preganglionic neurons at the T7–10 spinal levels and stimulate the release of cathecholamines from the adrenal medulla.

The interaction of galanin (GAL) with serotonin (5-HT) in the regulation of prolactin (PAL) secretion was investigated in urethaneanesthetized male rats. Intracerebroventricular administration of 5-HT (1 and 10 mu g) and GAL (1 mu g) caused an increase in plasma PRL levels, but co-administration of GAL did not show any additive effect on 5-HT-induced PRL secretion. Pretreatment with methysergide (0.25 mg/kg), a nonselective 5-HT1 and 5-HT2 receptor antagonist, partially inhibited the PRL increase induced by GAL. On the other hand, neither ketanserin (0.25 mg/kg), a selective 5-HT2 receptor antagonist, nor ICS 205-930 (0.25 mg/kg), a selective 5-HT3 receptor blocker, had any effect on GAL-induced increase in PRL secretion. Parachlorophenylalanine (300 mg/kg), a 5-HT synthesis inhibitor, however, caused a marked enhancement of PRL release induced by GAL, which was partially inhibited by a 5-HT neurotoxin, 5, 6-dihydroxytryptamine. Parachlorophenylalanine also caused a potentiation of 5-HT-induced PRL release, possibly by sensitizing 5-HT receptors. These findings suggest that 5-HT receptors are, at least partly, involved in GAL-induced PRL release in the rat.

Plasma GH levels were determined during a 75-g oral glucose tolerance test using a highly sensitive enzyme immunoassay. Most normal subjects and patients with varying degrees of impaired glucose tolerance showed a decrease in plasma GH levels during the first 60 min. A GH rise within 60 min was observed in 3 of 37 normal subjects. The incidence of the GH rise (8%) was significantly lower than that (40%) in control experiments after water loading. The median minimum GH levels were 0.15 and 0.14 micrograms/L after glucose and water loading, respectively. Plasma GH responses to glucose ingestion were not different between normal subjects and patients with glucose intolerance. After surgery, 12 of 16 patients with acromegaly showed low basal GH levels (less than 5.0 micrograms/L). Six of the 12 patients showed normal GH responses to glucose loading (median minimum GH level, 0.21 micrograms/L) and normal plasma insulin-like growth factor-I levels. Plasma GH levels were not suppressed below 1.0 micrograms/L in the remaining 6 acromegalic patients. Determination of plasma GH levels after glucose loading by the highly sensitive enzyme immunoassay is useful for evaluating the effect of surgical treatment of acromegaly.

Intracerebroventricular administration of galanin (GAL) potently evoked growth hormone (GH) secretion in conscious male rats. Pretreatments with neostigmine and cysteamine blunted the GAL-induced GH secretion. Pretreatment of animals with a specific anti-somatostatin serum significantly inhibited the GAL-induced GH secretion. On the contrary, GH-releasing hormone-induced GH secretion was significantly enhanced with cysteamine and anti-somatostatin serum. These results suggest that somatostatin is involved in GAL-induced GH secretion in rats.

The effects of cholinergic modulation by hexamethonium (HEX), tetraethylammonium (TEA), pirenzepine (PIR) and neostigmine on growth hormone (GH) secretion induced by galanin (GAL) were investigated in awake, freely moving male rats. Intracerebroventricular (i.c.v.) injection of GAL (0.6 nmol) caused a marked increase in plasma GH levels. Pretreatment with HEX (3 or 15 mg/kg BW), TEA (15 mg/kg BW) or PIR (0.5 mg/kg BW) significantly reduced the GAL-induced GH secretion. Pretreatment of animals with neostigmine (0.05 mg/kg BW) or with a specific antisomatostatin antiserum (10 microliters of 1:10 diluted with saline, i.c.v.) reversed the inhibition of GAL-induced GH secretion by HEX. These findings suggest that both nicotinic and muscarinic cholinergic mechanisms interact with the galanin-induced GH secretion by modulating hypothalamic somatostatin release.

Plasma alpha and TSH-beta subunit responses to iv administration of GHRH were examined in 19 patients with active acromegaly. In 4 patients (21%), plasma alpha subunit levels were increased over 50% of basal levels after administration of GHRH, whereas plasma TSH-beta subunit levels were increased in response to GHRH in another 5 patients (26%). No patient showed simultaneous increases of alpha and beta subunits. After successful surgery, alpha and TSH-beta subunits did not respond to GHRH. These findings support the idea that some pituitary adenomas in acromegaly co-secrete GH and either alpha subunit or TSH-beta subunit.

The mechanism by which galanin (GAL) stimulates prolactin (PRL) secretion was investigated in urethane-anesthetized male rats. The PRL release induced by intracerebroventricular (i.c.v.) injection of porcine GAL (pGAL) was similar to that induced by rat GAL. The PRL release induced by pGAL was partially blocked by alpha-adrenergic antagonists, phentolamine (1 microgram/rat, i.c.v.; 29.1 +/- 4.5 ng/ml vs control 66.9 +/- 10.2 ng/ml, P less than 0.01) and tolazoline (1 microgram/rat, i.c.v.; 25.9 +/- 4.4 ng/ml vs control 59.6 +/- 10.9 ng/ml, P less than 0.05). Neither propranolol (1 microgram/rat, i.c.v.), a beta-adrenergic antagonist, nor prazosin (1 microgram/rat, i.c.v.), an alpha 1-adrenergic antagonist, inhibited pGAL-induced PRL release. Naloxone (125 micrograms/100 g body wt., i.v. 30 min before), an opiate antagonist, also inhibited pGAL-induced PRL release (25.9 +/- 4.0 ng/ml vs 59.1 +/- 7.2 ng/ml, P less than 0.01). Combined treatment with naloxone and phentolamine caused greater inhibition of pGAL-induced PRL release than did phentolamine alone (10.3 +/- 1.5 ng/ml vs 23.2 +/- 4.7 ng/ml, P less than 0.05), but the inhibition was similar to that induced by naloxone alone. These findings suggest that alpha 2-adrenergic and opioidergic mechanisms are involved in PRL release induced by GAL.

The effect of galanin, a newly identified neuropeptide, on pituitary prolactin (PRL) secretion was examined in the rat. Intracerebroventricular (i.c.v.) injection of all 5 doses of galanin (0.4, 1, 2, 5 and 10 micrograms/rat) raised plasma PRL levels in urethane-anesthetized rats. Galanin injection (2 micrograms/rat, i.c.v.) also increased plasma PRL levels in conscious rats. The intermediate dose of galanin (2 micrograms/rat, i.c.v.) produced a greater response in plasma PRL levels than either smaller or larger doses of galanin. Intravenous injection of galanin did not affect plasma PRL levels. Passive immunization with specific anti-vasoactive intestinal polypeptide (VIP) rabbit serum suppressed plasma PRL response to galanin (2 micrograms/rat, i.c.v.) in anesthetized rats. These findings indicate that central galanin has a stimulatory role in pituitary PRL secretion via the hypothalamus in the rat and that VIP may be involved in rat PRL release induced by galanin.

Noradrenergic mechanisms have a stimulatory role in regulating prolactin (PRL) secretion in the rat. We investigated the mechanism by which the alpha 2-adrenergic system stimulates PRL release in urethane-anesthetized male rats. Intracerebroventricular injection of norepinephrine (2 micrograms/rat) or epinephrine (100 ng and 1 microgram/rat) caused an increase in plasma PRL levels. The PRL increase induced by epinephrine was much greater than that by norepinephrine. Intracerebroventricular injection of phentolamine (1 microgram/rat), an alpha-antagonist, blunted the plasma PRL increase induced by epinephrine (100 ng intracerebroventricularly). Plasma PRL levels were increased by intravenous injection of alpha 2-agonists, clonidine (15 micrograms/100 g of body wt), and xylazine (200 micrograms/100 g of body wt). Plasma PRL increase induced by clonidine or xylazine was suppressed by intravenous injection of naloxone (125 micrograms/100 g of body wt), an opiate antagonist. These findings suggest that alpha 2-adrenergic mechanisms stimulate pituitary PRL secretion, at least partly, by activating endogenous opioid peptides in the rat.

Intracerebroventricular (icv) injection of L-3,4-dihydroxyphenylserine (L-DOPS) (50 and 250 micrograms/rat) raised in a dose-related manner both plasma prolactin (PRL) and CSF norepinephrine (NE) in urethane-anesthetized male rats. Intravenous (iv) injection of larger doses of L-DOPS (5 and 10 mg/100 g BW) slightly but significantly increased plasma PRL and CSF NE. L-DOPS injection (50 micrograms/rat, icv or 5 mg/100 g BW, iv) also raised plasma PRL in conscious rats. There was a good correlation (r = 0.74) between CSF NE and peak plasma PRL in the anesthetized animals. Propranolol (100 micrograms/100 g BW, iv) inhibited plasma PRL responses to L-DOPS (50 micrograms/rat, icv) and NE injection (1 microgram/rat, icv) raised plasma PRL in anesthetized animals. These findings indicate that L-DOPS stimulates PRL secretion via central noradrenergic mechanisms in the rat.

Escape from sodium and potassium retaining actions of aspirin-like drugs used in a patient with Bartter's syndrome. An analysis was done with regard to the mode of escapes from sodium and potassium retaining actions of aspirin-like drugs in a patient with Bartter's syndrome. In the indomethacin therapy of the syndrome, there was a delay in the initiation of potassium escape as compared to sodium escape, whereas no delay was seen in the ibuprofen therapy. This delay was probably related to the direct or indirect inhibition of sodium-potassium exchange in the distal nephrons. The course of aspirin therapy went midway between the above two. In the spironolactone therapy, the mode of escape was a mirror image of the one in the indomethacin therapy. Also, in a patient with rheumatoid arthritis, but without Bartter's syndrome, the escapes from the effects of indomethacin were seen. In order to understand the effect of these drugs on potassium excretion in Bartter's syndrome, some other intrarenal events, such as the influence on chloride transport in the loop of Henle leading to potassium conservation, may have to be considered.

We investigated the role of intramuscular enzymatic changes in the development of muscular weakness in rats suffering from experimental allergic neuritis. At an initial stage without apparent clinical symptoms, enzymatic changes of similar types occurred in the muscles of the forelimbs and hind limbs. At a later stage when the weakness appeared in the hind limb but not in the forelimb, dissociation of the pattern of the enzymatic changes occurred between the two limbs. Comparison of the intramuscular enzymatic changes between the two stages and between the two limbs suggested that the increased activities of aminopeptidases and endopeptidases play some important roles in the development of muscular weakness in this experimental model. Low molecular weight protease inhibitors may thus be worthy of a trial in this disease condition.

Brain opiatergic, alpha-adrenergic and GABAergic mechanisms are known to play a stimulating role in growth hormone (GH) secretion in the rat. Plasma GH levels were increased by intracerebroventricular (i.c.v.) injection of somatostatin-14 (SRIF-14, 5 micrograms/rat) in conscious rats. GH release induced by i.c.v. SRIF-14 was blunted by either intravenous (i.v.) injection of phenoxybenzamine (500 micrograms/100 g b. wt.), an alpha-adrenergic blocker, or picrotoxin (150 micrograms/100 g b. wt.), a GABA antagonist, in the rat. On the other hand, i.v. injection of naloxone (125 micrograms/100 g b. wt.), an opiate antagonist, did not affect GH release induced by i.c.v. SRIF-14. These findings suggest that alpha-adrenergic and GABAergic mechanisms but not opiatergic mechanisms are involved in central SRIF-induced GH secretion in the rat.

Urinary excretion of growth hormone during night-time was measured by a highly sensitive enzyme immunoassay in 6 normal men for 18–24 days. Urinary GH excretion distributed widely from 0.12 to 4.7 pg/μmol creatinine and the coefficient of variation in each subject ranged from 37 to 57% (mean 49%). Urinary excretion of albumin and α1-microglobulin also showed moderate day-to-day variations (mean coefficients of variation: 37 and 42%, respectively). No correlation was found among urinary excretion of GH, albumin and α1-microglobulin. Plasma and urinary GH levels were determined every 5 min and 2 h, respectively, from 09.00 h to 17.00 h in 4 normal men. Urinary GH excretion every 2 h during daytime closely reflected the change of plasma GH levels in each subject, suggesting that physiological GH secretory dynamics are reflected on the urinary GH excretion. Repeated measurements of urinary GH excretion are required to evaluate GH secretory capacity.

The effect of L-threo-3,4-dihydroxyphenylserine (L-DOPS) on norepinephrine (NE) levels in plasma and CSF was examined in urethane-anesthetized rats. Intravenous injection of L-DOPS (0.5, 1, and 10 mg/100 g body wt) raised plasma NE levels in a dose-related manner whereas CSF NE levels were significantly increased only by the largest dose of L-DOPS. Intracerebroventricular injection of L-DOPS (50 and 250 μg/rat) dose-relatedly raised CSF NE levels whereas plasma NE levels were slightly increased by a larger dose of L-DOPS. These findings may indicate that L-DOPS stimulates central noradrenergic mechanisms in the rat although a large dose of L-DOPS is required for peripheral administration.