Surgical management for glossopharyngeal neuralgia associated with cardiac syncope: two case reports.

Two patients with glossopharyngeal neuralgia associated with cardiac syncope were treated with temporary cardiac pacemakers for cardiac syncope and then microvascular decompression. The offending arteries were the posterior inferior cerebellar artery in one patient and the anterior inferior cerebellar artery in the other. The offending arteries were attached to the glossopharyngeal nerve and the vagal nerve at the root entry zones. After surgery, the patients were free from neuralgia and cardiac syncope did not occur after the pacemakers were extracted. Implantation of a temporary cardiac pacemaker in the perioperative period ensures safe microvascular decompression.

ST segment elevation in the right precordial leads following administration of class Ic antiarrhythmic drugs.

Electrocardiographic changes were evaluated retrospectively in five patients without previous episodes of syncope or ventricular fibrillation who developed abnormal ST segment elevation mimicking the Brugada syndrome in leads V1-V3 after the administration of class Ic antiarrhythmic drugs. Pilsicainide (four patients) or flecainide (one patient) were administered orally for the treatment of symptomatic paroxysmal atrial fibrillation or premature atrial contractions. The QRS duration, QTc, and JT intervals on 12 lead surface ECG before administration of these drugs were all within normal range. After administration of the drugs, coved-type ST segment elevation in the right precordial leads was observed with mild QRS prolongation, but there were no apparent changes in JT intervals. No serious arrhythmias were observed during the follow up periods. Since ST segment elevation with mild QRS prolongation was observed with both pilsicainide and flecainide, strong sodium channel blocking effects in the depolarisation may have been the main factors responsible for the ECG changes. As the relation between ST segment elevation and the incidence of serious arrhythmias has not yet been sufficiently clarified, electrocardiographic changes should be closely monitored whenever class Ic drugs are given.

Origin of Ca2+ necessary for carbachol-induced contraction in longitudinal muscle of the proximal colon of rats.

The origin of Ca2+ necessary for carbachol (CCh)-induced contraction of longitudinal muscle of the proximal colon of rats was studied. CCh induced contraction of the muscle consisting of two phases, phasic and tonic phases, with a concomitant biphasic increase in [Ca2+]i. After removal of Ca2+ from the bathing solution of the colonic segments, CCh-induced contraction was rapidly inhibited; there was almost complete inhibition 1 min after the removal. Nicardipine, a blocker of voltage-dependent calcium channel, also significantly inhibited CCh-induced contraction. On the other hand, treatment of the colonic segments with thapsigargin, an inhibitor of sarcoplasmic reticulum (SR) Ca2+-ATPase, did not significantly affect the contraction except causing a slight decrease in the rate of contraction. These results suggest that Ca> entering through voltage-dependent calcium channels, but not released from SR, is essential for CCh-induced contraction of longitudinal muscle of the proximal colon of rats. This strict dependency of the CCh-induced contraction on extracellular Ca2+ was discussed in relation to the results obtained in the fundus of rats.

Relationship between toxicity and cadmium accumulation in rats given low amounts of cadmium chloride or cadmium-polluted rice for 22 months.

To clarify toxic effects of long-term oral administration of low dose cadmium (Cd) on the liver and kidney, six groups of female Sprague-Dawley rats were fed a diet containing Cd-polluted rice or CdCl2 at concentrations up to 40 ppm, and killed after 12, 18, and 22 months. With toxicological parameters, including histopathology, there was no evidence of Cd-related hepato-renal toxicity, despite a slight decrease of mean corpuscular volume and mean corpuscular hemoglobin of red blood cells with 40 ppm CdCl2. Dose-dependent accumulation of Cd was observed in the liver and kidneys with peak levels of 130 +/- 42 micrograms/g and 120 +/- 20 micrograms/g, respectively, at 18 months in animals treated with 40 ppm CdCl2. A dose-dependent increase in urinary Cd levels became evident with time. Induction of metallothionein (MT) was also observed in the liver and kidney with a high correlation to the corresponding Cd levels. In the proximal renal tubular epithelia of 40 ppm CdCl2-treated rats at 22 months, prominent accumulation of Cd was observed in secondary lysosomes associated with MT deposits in their exocytotic residual bodies. The results demonstrated that, in contrast to the case with high-dose Cd-administration, renal toxicity is not induced by long-term oral administration of low amounts of Cd, although tissue accumulation does occur. Possible protective mechanisms may be operating.

Circadian variation of vasovagal syncope.

INTRODUCTION: Circadian patterns have been demonstrated for several cardiovascular catastrophes. Chronobiologic factors play a role in the emergence of vasovagal syncope (VVS); however, diurnal variation of syncopal episodes in VVS has not been reported previously. METHODS AND RESULTS: We assessed daily distribution of the time of syncopal episodes in VVS. Time of syncope could be determined in 80 episodes in 54 patients (32 men and 22 women; mean age 37 years, range 12 to 67). Patients who were prescribed beta blockers or vasodilators, and who had syncopes related to alcohol intake, were excluded from the study. Head-up tilt testing was performed in 53 patients. The distribution of the episodes of VVS in 3-hour intervals differed significantly from uniform occurrence (P < 0.0001), with a peak frequency between 6 A.M. and noon (67.5% of total episodes). In patients who had experienced the initial syncope in the morning, most (78%) of the next syncopal episodes also occurred in the morning. There was no significant correlation between the time of last syncopes and tilt testing results. CONCLUSION: We demonstrated a prominent circadian variation in the frequency of VVS, with a peak in the morning. Recognition of the daily distribution of VVS is useful for patient education and therapeutic strategy.

Inhibitory effects of chondroitin sulfate prepared from salmon nasal cartilage on fat storage in mice fed a high-fat diet.

OBJECTIVE: Chondroitin sulfate is an acidic polymer consisting of repeating D-glucuronic acid and D-N-acetylgalactosamine units, and the N-acetylgalactosamine is substituted with the sulfate at either the 4' or 6' position, with approximately one sulfate being present per disaccharide unit. The present study assessed the effects of chondroitin sulfate on the activity of pancreatic lipase and lipid uptake into brush border membrane vesicles of the rat small intestine in vitro, and on the degree of fat storage induced in mice by the oral administration of a high-fat diet for 8 weeks. DESIGN AND MEASUREMENTS: Experiments were carried out to clarify whether or not chondroitin sulfate inhibited pancreatic lipase activity in assay systems using triolein emulsified with phosphatidylcholine or gum arabic. In addition, the effects of chondroitin sulfate on lipid absorption by brush border membrane vesicles were examined. Moreover, mice were fed a high-fat diet and treated with chondroitin sulfate for 8 weeks. RESULTS: Chondroitin sulfate dose-dependently inhibited the pancreatic lipase activity in an assay system using triolein emulsified with phosphatidylcholine. In addition, chondroitin sulfate inhibited the palmitic acid uptake into the brush border membrane vesicles of the rat jejunum. Chondroitin sulfate caused the reduction of body weight and parametrial adipose tissue weight, and prevention of fatty liver and hyperlipidemia in mice fed a high-fat diet. CONCLUSION: The reduction of fat storage and the antihyperlipidemic action of chondroitin sulfate might be due to the inhibition of small intestinal absorption of dietary fat through the inhibition of pancreatic lipase activity and fatty acid uptake through brush border membrane.

[Methodology of 80 degrees head-up tilt testing with and without low dose isoproterenol provocation in Japanese patients with neurally mediated syncope].

The usefulness of 80 degrees head-up tilt testing with and without low dose isoproterenol provocation was evaluated for the diagnosis of neurally mediated syncope (NMS) in Japanese. Head-up tilt testing was performed in 114 consecutive patients with clinical diagnoses of NMS (68 men, 46 women, mean age 46 +/- 21 years), and 57 times in 36 healthy volunteers (26 men, 10 women, mean age 31 +/- 8 years) who had no history of syncope or presyncope. Head-up tilt testing used an 80 degrees angle for 30 minutes (passive tilt), and if the passive tilt resulted in negative response, isoproterenol was infused at 0.01-0.02 microgram/kg/min and the tilt repeated for 10 minutes (isoproterenol tilt). A positive response was defined as the development of syncope or a presyncopal state associated with hypotension, bradycardia or cardiac arrest. The sensitivities of passive tilt testing for a positive response after 5-, 10-, 15-, 20-, 25- and 30-minute tilting were 1%, 9%, 14%, 19%, 24%, and 28%, respectively, and specificities after 5-, 10-, 15-, 20-, 25- and 30-minute tilting were 100%, 95%, 91%, 88%, 86%, and 84%, respectively. The sensitivities of isoproterenol tilt testing with 0.01 and 0.02 microgram/kg/min were increased to 37% and 48%, respectively. This improvement was statistically significant between the passive tilt and isoproterenol tilt testing with a dose of 0.02 microgram/kg/min (p < 0.01). However, specificities were comparable with those of the passive tilt testing (84% and 82%, respectively). In conclusion, 80 degrees passive tilt testing for 30 minutes showed a low sensitivity (28%) but acceptable specificity (84%). Low-dose isoproterenol provocation was useful for improving sensitivity (48%) while maintaining a comparable specificity (82%).

Arrhythmogenic right ventricular cardiomyopathy with an initial manifestation of severe left ventricular impairment and normal contraction of the right ventricle.

A case of arrhythmogenic right ventricular cardiomyopathy (ARVC) with an initial manifestation of severe impairment of the left ventricle (LV) and normal contraction of the right ventricle (RV) is presented. A 43-year-old man was admitted to hospital because of congestive heart failure following a common cold. The LV function was diffusely and severely hypokinetic. Coronary arteriogram revealed normal vessels. An endomyocardial biopsy specimen obtained from the RV septum revealed mild infiltration of lymphocytes with focal myocytes necrosis and so healing myocarditis was suspected. The specimen did not include any fatty replacement of myocytes. Since then, the patient suffered from recurrent congestive heart failure as well as nonsustained ventricular tachycardia and required frequent hospitalization. Progressive impairment, dilation, and thinning of both ventricles were observed on serial echocardiographic examinations. Although the RV gradually enlarged and became impaired, severe dilatation and impairment of the LV has always been predominant in the patient's clinical course. After medical follow-up for 10 years, he died suddenly of ventricular fibrillation and pump failure. The autopsy revealed extensive fibrofatty replacement of myocytes in both the ventricles, extending from the outer layer to the inner layer of myocardium in the RV and to the middle layer in the LV. These features were compatible with arrhythmogenic right ventricular cardiomyopathy or perimyocarditis, although only the rightsided bundle of the interventricular septum was completely replaced by fatty tissue, which can not be explained as a sequel of perimyocarditis. Moreover, apoptosis was present in the myocyte nuclei of the myocardial layers bordering the area of fatty replacement. Therefore, myocarditis may have triggered or accelerated the process of apoptosis leading to ARVC.

Assessment of renal toxicity by analysis of regeneration of tubular epithelium in rats given low-dose cadmium chloride or cadmium-polluted rice for 22 months.

To determine whether low-dose oral administration of cadmium (Cd) induces renal toxicity, six groups of female Sprague-Dawley rats were fed a diet containing low amounts of CdCl2 or Cd-polluted rice at concentrations up to 40 ppm, and were killed after 12, 18, and 22 months (experiment 1). In addition to the determination of cortical Cd levels and histopathological assessment of kidneys, labeling indices (LIs) for proliferating cell nuclear antigen (PCNA) in the renal cortical tubular epithelium of Cd-treated rats were determined as a measure of regenerative activity. For comparison, the kidneys of rats given diets containing small to large amounts of CdCl2 up to 600 ppm for 4 months were similarly examined (experiment 2). Animals in experiment 1 demonstrated spontaneous chronic nephropathy and fluctuation in the tubular PCNA LI, but these findings were not correlated with renal Cd levels at 22 months. PCNA LI on the other hand, appeared to be linked to the severity of chronic nephropathy. In experiment 2, levels of CdCl2 of 200 ppm or more clearly induced degeneration and apoptosis of proximal tubules with high correlations between renal Cd levels, PCNA LI, and the severity of tubular degeneration. The results demonstrated that, in contrast to high-dose Cd administration, treatment with 40 ppm or less for 22 months did not influence tubular regeneration as a component of nonspecific chronic nephropathy, suggesting that long-term oral administration of low levels of Cd does not injure renal tubules in female rats.

Does an early increase in heart rate during tilting predict the results of passive tilt testing?

Head-up tilt testing is a useful but time-consuming procedure. If we could accurately predict the tilt testing results; we would be able to substantially shorten the duration of tilt protocol. To clarify the hypothesis that an early increase in heart rate (HR) during tilting can predict the passive tilt results in our protocol (80-degree angle for 30 minutes), we studied 115 consecutive patients (72 men, 43 women, mean age 46 +/- 19 years) who were clinically diagnosed with neurally mediated syncope. Twenty-nine (25%) patients had a positive tilt test (P group), whereas 86 (75%) patients had a negative test (N group). The early HR increase was defined as the maximum HR during the first 5 minutes of tilting minus the resting HR before tilting. The early HR increase was significantly higher in the P group (23.8 +/- 9.5 beats/min) than in the N group (17.5 +/- 8.2 beats/min, P = 0.0008), but it was negatively correlated with the tilt duration to positive response (r = -0.52, P = 0.0032) and the patient age in the entire study population (r = 0.62, P < 0.0001). Results of multiple regression analysis indicated that age, tilt result, and tilt duration were independently associated with the early HR increase. As a result, an early HR increase > or = 18 beats/min, the best apparent cut-off point obtained in our study, was a sensitive (100%) marker for prediction of a positive response at < or = 15 minutes of tilting, but it showed a low specificity (61%). In conclusion, an early HR increase during 80-degree tilting may be only predictive for a positive result < or = 15 minutes because it depends on the tilt duration to a positive response and patient age.

Wax ester-synthesizing activity of lipases.

The synthesis/hydrolysis of wax esters was studied in an aqueous solution using purified rat pancreatic lipase, porcine pancreatic carboxylester lipase, and Pseudomonas fluorescens lipase. The equilibrium between wax ester synthesis and hydrolysis favored ester formation at neutral pH. The synthesizing activities were measured using free fatty acid or triacylglycerol as the acyl donor and an equimolar amount of long-chain alcohol as the acyl acceptor. When oleic acid and hexadecanol emulsified with gum arabic were incubated with these lipases, wax ester was synthesized, in a dose- and time-dependent manner, and the apparent equilibrium ratio of palmityl oleate/free oleic acid was about 0.9/0.1. These lipases catalyzed the hydrolysis of palmityl oleate emulsified with gum arabic, and the apparent equilibrium ratio of palmityl oleate/free oleic acid was also about 0.9/0.1. The apparent equilibrium ratio of wax ester/free fatty acid catalyzed by lipase depended on incubation pH and fatty alcohol chain length. When equimolar amounts of trioleoylglycerol and fatty acyl alcohol were incubated with pancreatic lipase, carboxylester lipase, or P. fluorescens lipase, wax esters were synthesized dose-dependently. These results suggest that lipases can catalyze the synthesis of wax esters from free fatty acids or through degradation of triacylglycerol in an aqueous medium.

Fatty acid alcohol ester-synthesizing activity of lipoprotein lipase.

The fatty acid alcohol ester-synthesizing activity of lipoprotein lipase (LPL) was characterized using bovine milk LPL. Synthesizing activities were determined in an aqueous medium using oleic acid or trioleylglycerol as the acyl donor and equimolar amounts of long-chain alcohols as the acyl acceptor. When oleic acid and hexadecanol emulsified with gum arabic were incubated with LPL, palmityl oleate was synthesized, in a time- and dose-dependent manner. Apo-very low density lipoprotein (apoVLDL) stimulated LPL-catalyzed palmityl oleate synthesis. The apparent equilibrium ratio of fatty acid alcohol ester/oleic acid was estimated using a high concentration of LPL and a long (20 h) incubation period. The equilibrium ratio was affected by the incubation pH and the alcohol chain length. When the incubation pH was below pH 7.0 and long chain fatty acyl alcohols were used as substrates, the fatty acid alcohol ester/free fatty acid equilibrium ratio favored ester formation, with an apparent equilibrium ratio of fatty acid alcohol ester/fatty acid of about 0.9/0.1. The equilibrium ratio decreased sharply at alkaline pH (above pH 8.0). The ratio also decreased when fatty alcohols with acyl chains shorter than dodecanol were used. When a trioleoylglycerol/fatty acyl alcohol emulsion was incubated with LPL, fatty acid alcohol esters were synthesized in a dose- and time-dependent fashion. Fatty acid alcohol esters were easily synthesized from trioleoylglycerol when fatty alcohols with acyl chains longer than dodecanol were used, but synthesis was decreased with fatty alcohols with acyl chain lengths shorter than decanol, and little synthesizing activity was detected with shorter-chain fatty alcohols such as butanol or ethanol.

Tissue distribution of cadmium in rats given minimum amounts of cadmium-polluted rice or cadmium chloride for 8 months.

To investigate the relationship between cadmium (Cd) toxicity, intestinal absorption, and its distribution to various tissues in rats treated orally with minimum amounts of Cd, 14 female rats per dose group per time point were given diets consisting of 28% purified diet and 72% ordinary rice containing Cd-polluted rice (0. 02, 0.04, 0.12, or 1.01 ppm of Cd) or CdCl(2) (5.08, 19.8, or 40.0 ppm of Cd) for up to 8 months. At 1, 4, and 8 months after the commencement of Cd treatment, seven rats per group were euthanized for pathological examinations to determine the Cd concentrations in the liver and kidneys and metallothionein (MT) in the liver, kidneys, intestinal mucosa, serum, and urine. One week before each period of 1, 4, and 8 months, the remaining seven rats in each group were administered a single dosage of (109)Cd, a tracer, to match the amounts of the designated Cd doses (about 1.2 to 2400 microg/kg body wt). They were euthanized 5 days later to determine the distribution of Cd to various tissues. No Cd-related toxic changes were observed. The concentrations of Cd in the liver and kidneys at any time point and MT in the liver, kidney, serum, and urine at 4 and 8 months increased dose-dependently, whereas MT in the intestinal mucosa did not alter markedly at any time point. The distribution rates of Cd to the liver increased dose-dependently (40% at lower doses to 60% at higher doses), whereas those to the kidney decreased dose-dependently (20% at lower doses to 10% at higher doses). The Cd retention rates 5 days after (109)Cd administration (amounts of Cd in various tissues/amounts of Cd administered) ranged from 0.2 to 1. 0% at any time point. These results suggest that the distribution of Cd to the liver and kidneys after the oral administration vary depending on the dosage levels of Cd. The difference of the distribution pattern of Cd to the liver and kidney is probably due to the difference in the form of the absorbed Cd, i.e., free ion or Cd-MT complex, although not closely related to the MT in the intestinal mucosa.

Acute performance of steroid-eluting screw-in leads for atrial free wall pacing.

The aim of this study was to clarify the acute performance of steroid-eluting screw-in leads in comparison with that of nonsteroid screw-in leads for atrial free wall pacing. In 114 cases (68 males, 46 females, average age 70 years) with atrial free wall pacing by screw-in leads, pacing thresholds and P-wave amplitudes were compared at the time of implantation and 1 week later between 68 cases of nonsteroid and 46 cases of steroid-eluting screw-in leads. No significant differences were seen between the 2 groups at implantation in either voltage or current thresholds measured at pulse widths of 0.1, 0.3, 0.6, 1.0, 2.0 ms, or P-wave amplitudes. Pulse width thresholds at outputs of 2.5 V and 5.0 V were significantly lower for steroid leads 1 week after implantation (2.5 V: 0.34+/-0.27 ms nonsteroid vs. 0.12+/-0.08 ms steroid, p<0.001; 5.0 V: 0.12+/-0.08 ms nonsteroid vs. 0.06+/-0.02 ms steroid, p<0.01). P-wave amplitudes after 1 week were significantly higher for steroid leads (2.6+/-0.7 mV nonsteroid vs 3.0+/-1.2 mV steroid, p<0.001). Threshold rise, including pacing failure, was observed in 15 (22%) of the non-steroid leads, but in only 1 (2%) of the steroid leads. In conclusion, steroid-eluting screw-in leads suppress the acute rise of pacing thresholds in the right atrial free wall and their acute performance is better than that of non-steroid leads. These results suggest that appropriate low-output atrial pacing is feasible immediately after implantation.

Analysis of heart rate variability during head-up tilt testing in a patient with idiopathic postural orthostatic tachycardia syndrome (POTS).

A 16-year-old boy was diagnosed with idiopathic postural orthostatic tachycardia syndrome (POTS) during head-up tilt testing. During a passive tilt, the patient's heart rate (HR) increased by 30 beats/min within 5 min. After 25 min of tilting, his HR further increased to 133 beats/min and he began to complain of lightheadedness and weakness without hypotension. Power spectral analysis of HR variability during the tilt test revealed that the ratio of low and high frequency powers increased with the onset of orthostatic intolerance. Propranolol (10mg every morning) dramatically alleviated his clinical symptoms, and he has been asymptomatic with gaining weight after discontinuing his crowded train commuting.

Poor reproducibility of false-positive tilt testing results in healthy volunteers.

Positive responses to head-up tilt testing occur in healthy subjects. However, the reproducibility of "false-positive" tilt testing results has not been clarified. To study the reproducibility of "false-positive" responses, we prospectively performed 2 tilt tests separated by 1 to 10 (mean 3.2) weeks in 20 healthy males aged 23 to 40 years (mean 30 years). The baseline tilt test (80 degrees for 30 minutes) ended positive in 4 (20%) subjects on the initial test and 2 (10%) on the second test with only 1 (5%) who had consecutive positive responses. No additional positive responses were noted during the isoproterenol (0.01 microgram/kg/min)-tilt test for 10 minutes. We demonstrated that a false-positive response occurred in 5 (25%) of 20 young males who underwent 2 tilt tests, however, only 1 (5%) subject had consecutive positive responses. Poor reproducibility may be characteristic of false-positive responses in head-up tilt testing.

Relationship between hormone-sensitive lipolysis and lipase activity in rat fat cells.

An assay for total hormone-sensitive lipase (HSL) in rat fat cells was devised in which fat-associated HSL was solubilized with ether, and triolein or cholesteryloleate was used as substrate. Norepinephrine (NE) caused marked release of glycerol from fat cells but did not activate HSL as estimated using triolein or cholesteryloleate as substrate. Propranolol, a beta-blocker, inhibited NE-induced lipolysis in fat cells without a concomitant reduction in HSL activity. The antilipolytic action of insulin on NE-induced lipolysis could not be explained by a decrease in HSL activity. Neither ACTH-induced lipolysis in fat cells nor its inhibition by insulin was accompanied by matching fluctuations in HSL activity. These results indicate that neither NE and ACTH-induced lipolysis in fat cells, nor the antilipolytic actions of propranolol and insulin, involve fluctuations in HSL activity.

Runaway pacemaker caused by a stuck accelerometer.

We report a case of runaway pacemaker with a ventricular pacing rate of 190 beats/min. The runaway occurred when the accelerometer became stuck due to the magnet application during VVIR pacing. Runaways in modern pacemakers are particularly rare, but they do still occur. The best solution for this phenomenon is generator replacement.