Analysis of wear, wear particles, and reduced inflammatory potential of vitamin E ultrahigh-molecular-weight polyethylene for use in total joint replacement.

Vitamin E (VE) has been added to ultrahigh-molecular-weight polyethylene (UHMWPE) acetabular cups and tibial trays primarily to reduce oxidative damage to the polymer. The aim of this study was to investigate the relative wear rates of UHMWPE-containing VE compared with virgin UHMWPE. The ability of VE to reduce the amount of inflammatory cytokines produced from stimulated peripheral blood mononuclear cells (PBMNCs) was also investigated. Stimulation was achieved by exposure of PBMNCs to either lipoplysaccharide (LPS) or VE-containing UHMWPE (VE-UHMWPE). In the present study, results showed that the wear rates of UHMWPE with or without VE were not significantly different. Particles generated by UHMWPE with and without VE were not significantly different in size distribution. The production of osteolytic mediators, tumor necrosis factor-alpha, interleukin 1ß (IL-ß), IL-6, and IL-8 were significantly reduced in (PBMNCs) stimulated with either LPS + VE compared with LPS or VE-UHMWPE particles compared to virgin UHMWPE particles. This trend was also observed when VE was added as a liquid to UHMWPE wear particle-stimulated PBMNCs. The exact mechanism of how VE affects the release of inflammatory mediators from particle-stimulated macrophages is not yet understood. It is likely to involve the anti-inflammatory and/or antioxidant effects of VE.

Shortening of conduction time over arborized atrioventricular accessory pathway with Mahaim fibers physiology just before interruption during radiofrequency ablation.

A 21-year-old woman had paroxysmal wide QRS tachycardia with a left bundle branch block configuration and a retrograde conducted P wave just behind the QRS complex. An electrophysiological study revealed antidromic atrioventricular tachycardia involving an atrioventricular connection with decremental conduction as the anterograde limb and normal atrioventricular node as the retrograde limb. During constant pacing from the high right atrium (HRA) at the cycle length (CL) of 600 ms, the QRS configurations were not identical to those during the wide QRS tachycardia or constant pacing at the CL of less than 500 ms. The process by which this arborized atrioventricular accessory pathway with the Mahaim fibers physiology was interrupted by radiofrequency catheter ablation is described. Radiofrequency energy was delivered to the site recording a Mahaim potential at the tricuspid annulus during constant pacing from the HRA at the CL of 429 ms. The stimulus-QRS interval gradually shortened as it reached the power plateau without changing the preexcited QRS configuration. Shortening of the conduction time over the Mahiam pathway might have resulted in changing of the propagation from a slow to fast conduction zone or acceleration in response to thermal effect in a node-like structure on the atrial insertion site.

Electrophysiological determinants of persistent dual atrioventricular nodal pathway physiology after slow pathway ablation in atrioventricular nodal reentrant tachycardia.

UNLABELLED: The purpose of this study was to examine the electrophysiological determinants of the elimination of recurrent atrioventricular nodal reentrant tachycardia (AVNRT) despite the persistence of dual AV nodal pathway physiology or single echo beats after ablation procedures. The study included 26 patients with common AVNRT who had undergone successful ablation treatment and no long-term recurrence of AVNRT. The slow pathway potential was targeted, and the endpoint of ablation was one echo during atrial extrastimulus testing (ET) with isoproterenol. Persistent dual pathways physiology or single echoes were present in 12 patients (group I) and absent in 16 (group II) after ablation. The number of anterograde AV nodal pathways and maximum AH interval (Max AH) during ET were measured before and after ablation, and ventriculoatrial conduction during ventricular pacing was examined. RESULTS: (1) multiple AV nodal pathways were more frequently observed in group I than in group II (50.0% vs 7%, P < 0.05); (2) Max AH decreased significantly after ablation in both groups (309 +/- 157 vs 171 +/- 53 ms in group II; P < 0.01, and 409 +/- 65 vs 274 +/- 86 ms in group I; P < 0.001); and (3) retrograde dual pathway conduction was more common in group I than in group II. These data suggest the presence of nonuniform conductive properties of the AV node in group I and that ablation targeting the slow pathway potential prevents recurrences of AVNRT by eliminating the pathway with the longest conduction time.

Electrophysiological characteristics during slow pathway ablation of posterior atrioventricular junctional reentrant tachycardia.

The purpose of this study was to compare the electrophysiological characteristics of posterior and anterior atrioventricular junctional reentrant tachycardia (AVJRT) during radiofrequency (RF) catheter ablation of a slow pathway. Twenty-four patients with common AVJRT, including 4 posterior (P) and 20 anterior AVJRT (A) were studied. We analyzed the retrograde atrial activation sequence of junctional rhythm and the presence of transient HA block during slow pathway ablation. When HA block developed, the AH interval before ablation and immediately after the end of energy delivery was measured. Successful ablation sites were divided into three groups; high (H), middle (M), and low (L) from the His bundle to the floor of the coronary sinus orifice. The results were: (1) the number of successful ablation sites were H 0, M 1, L 3 in P and H 1, M 8, L 11 in A; (2) the HA interval during AVJRT in P was longer than that in A (109 +/- 48 ms vs 43 +/- 6 ms, P < 0.01); (3) the retrograde atrial activation sequence during junctional rhythm was strictly concordant with that during AVJRT in both groups, but HA block developed during slow pathway ablation more often in P than in A (100% vs 30%, P < 0.01); and (4) The AH interval did not lengthen after HA block developed in P. These data suggest that another pathway does exist from the AV node to the atrium in addition to anterograde fast pathway and slow pathway, and that this pathway is used as the retrograde limb of P.

Effect of radiofrequency catheter ablation on parasympathetic denervation: a comparison of three different ablation sites.

UNLABELLED: Radiofrequency (RF) catheter ablation of supraventricular tachycardias (SVT) has been shown to result in local parasympathetic denervation. The purpose of this study was to estimate the correlation between RF cumulative energy and parasympathetic denervation at three different ablation sites. METHODS: 45 patients who underwent RF ablation of 36 AV reentrant tachycardias and 9 AV nodal reentrant tachycardias were studied. Twenty patients had left free-wall accessory pathways (group L), 8 patients right free-wall accessory pathways (group R), and 17 patients septal accessory pathways (n = 8) or slow pathways (n = 9) (group S). Time and frequency domain analysis of heart rate variability on 24-hour ambulatory ECG recordings was performed before and after RF ablation. pNN50 and the high frequency (0.15 to 0.40 Hz, HF) component were measured to examine the effects on parasympathetic nerve activity. The values of delta pNN50 and delta HF were expressed as the percent change of pNN50 and HF that occurred after versus before RF ablation. RESULTS: Both pNN50 and HF significantly decreased after RF ablation in all three groups. In group S, there was a significant correlation between RF cumulative energy and delta pNN50 (r = 0.66, P < 0.01) or delta HF (r = 0.58, P < 0.05). In contrast, there was no correlation between RF cumulative energy and delta pNN50 or delta HF in either group L or group R. CONCLUSION: These data suggest that RF ablation produces parasympathetic denervation at all three sites along the mitral or tricuspid annulus and that parasympathetic fibers may be located predominantly in the septal area.

Calcium sensitizers in chronic heart failure: inotropic interventions-reservation to preservation.

Newly developed Ca2+ sensitizers possess different mechanisms of action on contractile machinery. Increasing maximal Ca(2+)-activated force in addition to enhancing Ca2+ sensitivity (MCI-154, EMD 53998, and EMD 57033) could exert pronounced positive inotropy and may provide a mechanoenergetic advantage over the classic Ca2+ mobilization in the chronically failing heart. EMD 53998 and EMD 57033 prolong crossbridge attachment time, resulting in negative lusitropy. In contrast, pimobendan, levosimendan, and MCI-154 accelerate left ventricular relaxation in heart failure, because Ca2+ sensitizing action of these agents may be prominent during the early phases of contraction. Therefore, Ca2+ sensitizers can avoid the legacy of problems associated with conventional inotropic interventions and may break through "reservation" to "preservation" in the treatment of chronic heart failure.

Effects of MCI-154, a calcium sensitizer, on left ventricular systolic and diastolic function in pacing-induced heart failure in the dog.

BACKGROUND: MCI-154 is a positive inotropic agent that increases the myofilament response to Ca2+. Whether MCI-154 has beneficial effects on left ventricular dysfunction in chronic heart failure is not known. We examined the effects of MCI-154 on left ventricular systolic and diastolic function in pacing-induced heart failure in dogs. METHODS AND RESULTS: We studied eight anesthetized dogs before and 2 to 4 weeks after rapid right ventricular pacing. Left cineventriculograms with simultaneous left ventricular pressures (tip manometer) were obtained before and during intravenous administration of MCI-154 (I.O. microgram.kg-1.min-1 for 15 minutes) in the control and heart-failure states. Left ventricular volume dynamics was derived from frame-by-frame (20-ms) analyses of left ventricular angiograms. In heart failure, left ventricular contractility as assessed by shifts of the end-systolic pressure-volume ratio, evaluated by inferior vena cava occlusion, was improved by MCI-154 (+ 1.94 mm Hg/mL, P < .05) to an extent similar to that in the control state (+2.47 mm Hg/mL, P < .05). MCI-154 also accelerated left ventricular relaxation, assessed by the time constant of isovolumic pressure decay (T1/2), in both states. The absolute decrease in T1/2 with MCI-154 in heart failure was significantly greater than in the control state (-8.2 versus -3.1 ms, P < .05). In heart failure, MCI-154 shifted the left ventricular diastolic pressure-volume relation clearly downward, suggesting increased diastolic distensibility. CONCLUSIONS: MCI-154 improved not only left ventricular systolic function but also diastolic relaxation and distensibility in a chronic heart failure model.

Regression of left ventricular hypertrophy with long-term treatment of nifedipine in systemic hypertension.

We investigated the regression of left ventricular (LV) hypertrophy with long-term treatment of nifedipine in patients with systemic hypertension. Echocardiograms of the LV were obtained in nine patients before and at a mean of 50 months (13-105 months) after nifedipine monotherapy (30-60 mg/day). Nifedipine significantly reduced both systolic and diastolic blood pressures (BP) by a mean of -46 mmHg and -21 mmHg, respectively. With systemic BP reduction, LV mass was significantly reduced by a mean of -15%, associated with a decrease in LV posterior wall thickness and end-diastolic dimension. There was no significant change in LV fractional shortening. We conclude that nifedipine may cause regression of LV hypertrophy in systemic hypertension, and that reversal of the increase in LV mass could be maintained during long-term nifedipine treatment.

[Which time constant of left ventricular relaxation is the most sensitive measure in acute myocardial ischemia?].

To investigate which time constant of isovolumic left ventricular pressure (LVP) decay is the most sensitive measure in acute myocardial ischemia, the time constant of isovolumic relaxation (IR) was calculated by two different models, the semilogarithmic model assuming a zero of LVP decline (TL) and an exponential model (Texp) with an asymptote (extrapolated baseline pressure to which LVP would fall if decay continued indefinitely), in 10 patients before and during ergonovine-induced vasospastic angina. Two time constants were derived from the exponential method as the times for LVP at peak negative dP/dt to decline by 1/e (Texp (1/e)) and by one half (Texp (1/2)). Three changes in LVP during isovolumic relaxation were analyzed and fitted to the two models described above: the LVP from the peak negative dP/dt 1) to when LVP fell to 5 mmHg above LV end-diastolic pressure (EDP), 2) until 40 msec had passed, and 3) to the LVP level 5 mmHg above LVEDP during coronary spasm. There were significant increases in TL, Texp (1/e) and Texp (1/2) in each period of the LVP during vasospastic angina. However, no significant change in Texp or asymptote was observed during angina. We concluded that TL measured by the semilogarithmic model assuming a zero of LVP decline and Texp (1/e) or Texp (1/2) derived from the exponential model are adequately sensitive for detecting acute myocardial ischemia due to coronary spasm.

Gastric ammonia has a potent ulcerogenic action on the rat stomach.

BACKGROUND: The pathophysiological mechanism by which Helicobacter pylori induces mucosal injury has not been clarified. The aim of this study was to investigate the role of urea, urease, and ammonia in rat gastric mucosal lesions using an ex vivo chamber model. METHODS: Two groups of rats, normotensive rats and those subjected to ischemia, were studied. The gastric mucosa was examined histologically and macroscopically, and the transmucosal potential difference was measured. RESULTS: Instillation of urea into the stomach generated ammonia in the presence of urease. The amount of ammonia was increased depending on the concentration of urea and was closely associated with the severity of the histological lesions. The exposure of the stomach to 15-60 mmol/L ammonium hydroxide induced both a reduction in transmucosal potential difference and microscopic damage to the gastric mucosa in normotensive rats. Moreover, 15-60 mmol/L ammonium hydroxide produced severe macroscopic gastric lesions in the rats subjected to ischemia. CONCLUSIONS: These results show that ammonia is deleterious to the gastric mucosa and suggest the importance of urea, urease, and ammonia in the pathophysiology of gastric diseases in H. pylori-infected patients.

[A case of oral tuberculosis suspected malignancy].

Oral tuberculosis with pulmonary tuberculosis is very rare in Japan. A 45-year old man admitted to our hospital because of spontaneous teeth extraction and pain in oral cavity for the past 3 months. The painful granulation in palate and fistel of 7th tooth root defect in right upper gum were observed. The diagnosis of oral tuberculosis was made by the histological examination of biopsy material and positive smear test for M. tuberculosis in surface of granulation. Chest X-ray showed multicavitary lesions in bilateral upper lobs and spread shadows in bilateral lower lung fields. He was treated with chemotherapy (INH, RFP, SM and EB) and with tube feeding. Five month's chemotherapy was needed to achieve cured granulation and negative smear test for M. tuberculosis in sputum. He was discharged 10 months after admission.

Link between Helicobacter pylori-associated gastritis and duodenal ulcer.

We examined the interrelationships among the degree of fundic mucosal atrophy, the prevalence of Helicobacter pylori in the gastric antrum, the gastric juice, and the duodenum with and without gastric metaplasia, in 20 duodenal ulcer patients and 20 non-duodenal ulcer patients. The detection rates of H. pylori in the antrum, the gastric juice, and the duodenum were significantly higher in duodenal ulcer patients (80%, 65%, and 60%) than in non-duodenal ulcer subjects (50%, 20%, and 5%). The frequency of H. pylori was significantly lower in the gastric juice (30%) and the duodenum (10%) in non-duodenal ulcer patients with antral H. pylori, compared with those in duodenal ulcer patients with antral H. pylori. All of seven patients with both gastric metaplasia and H. pylori infection in the duodenum had duodenal ulcer, whereas only 1 of 14 patients without either gastric metaplasia or H. pylori infection in the duodenum had duodenal ulcer. There was normal or mild atrophic mucosa in the fundus of duodenal ulcer patients with H. pylori in the antrum, whereas moderate or severe atrophic mucosa in non-duodenal ulcer patients with H. pylori gastritis. These results suggest that the preserved fundic mucosa, gastric metaplasia in the duodenum, and a greater load of H. pylori to the duodenum through the gastric juice may be prerequisites for the formation of duodenal ulcers.

[A recovered case of serious lung tuberculosis on wanderer].

This report is a case study of a vagrant whose state of tuberculosis showed noteworthy improvement due to clinical treatment. A 54-year-old male, vagrant, was admitted to the hospital in a state of preshock because of a serious stage of lung tuberculosis. The clinical course was severe, but after three months of intensive care the patient recovered. It was noted that the echocardiogram taken after recovery revealed improvement when compared with the one taken upon admission, which showed remarkable right ventricular overload. Furthermore, anti-tuberculosis agents proved to be very effective in this case. The patients respiratory functions improved more markedly than had been expected. The reason for reporting this case study is to bring attention to the improvements in the patient's clinical course and echocardiographic findings. These suggest that tuberculosis in vagrants may differ from the usual stage of tuberculosis diagnosed in elderly persons in terms of response to anti-tuberculosis agents and potential recovery.

Helicobacter pylori has an ulcerogenic action in the ischemic stomach of rats.

Helicobacter pylori (H. pylori) is now accepted as an important cause of chronic active gastritis. There also seems to be an association between the colonization of H. pylori in the gastric mucosa and peptic ulceration. However, it has not demonstrated that the instillation of H. pylori into the stomach produces the ulcerative gastric lesions in animals or humans. We carried out an experiment to study whether or not H. pylori has an ulcerogenic action in the ischemic stomach of rats, using an ex vivo gastric chamber. The rat stomachs were exposed to 1 ml of H. pylori solution (200 IU of urease/ml) and 1 ml of urea (400 mg/dl) for 60 min after the creation of ischemia in the stomach (by withdrawal of 3 ml of blood). The exposure of the stomach to both H. pylori and urea resulted in severe hemorrhagic gastric mucosal lesions with a marked decrease in potential difference (PD) with a concomitant increase in ammonia concentration in rats with ischemia, whereas gastric lesions and a fall in PD were hardly observed in rats without ischemia. These results have demonstrated that H. pylori has an ulcerogenic action on the stomach subjected to mucosal ischemia.

[The effect of heart rate on the time constant of isovolumic relaxation of the left ventricle].

A time constant (T) of the left ventricular isovolumic relaxation, which expresses the relaxation rate of the left ventricle, may be affected by change of the heart rate. There are few clinical reports concerning the relationship between T and heart rate. We studied the relationship between T and heart rate in 10 patients with normal coronary arteries and left ventricular function. Left ventricular pressure was measured using a catheter-tip manometer during right atrial pacing, which was performed at the rate of 10, 20, 40 beats/min in addition to the baseline rate, and finished at 140 or 150 beats/min. Two measurements were made for T.1) Tw from the slope of In (pressure) against time, and 2) Tb by exponential analysis which also estimated the asymptote. As the heart rate increased, both Tw and Tb gradually shortened (Tw: from 38.5 +/- 4.9 msec at the control heart rate to 28.9 +/- 5.6 msec at 140 or 150 beats/min; Tb: from 54.7 +/- 11.4 msec at the control heart rate to 34.9 +/- 5.7 msec at 140 or 150 beats/min). These findings suggest that left ventricular isovolumic relaxation is strongly affected by change of the heart rate in man.

[Relaxation and diastolic filling precisely evaluated in patients with left ventricular dysfunction].

To assess left ventricular (LV) diastolic function in patients with LV dysfunction, LV pressures (manometer tip) and biplane angiograms were analyzed for 27 patients with LV systolic dysfunction (EF < or = 0.45) (dilated cardiomyopathy or coronary artery disease) and 18 normal controls. LV volumes were obtained from frame-by-frame analyses of angiograms. LV relaxation was assessed by the time constant (T) of LV pressure decay. LV relaxation was impaired in patients with LV dysfunction, however, early diastolic filling assessed by the peak filling rate (PFR) and mean filling rate (MFR) during the rapid filling phase was maintained. Compared to the control group, early diastolic filling was significantly decreased in patients with LV dysfunction without mitral regurgitation (MR), but not in those with LV dysfunction with MR. In conclusion, although diastolic filling may be modified by MR, LV relaxation and early diastolic filling are essentially impaired in patients with LV dysfunction.

Generation of ammonia and mucosal lesion formation following hydrolysis of urea by urease in the rat stomach.

We examined the morphological changes in gastric mucosa and the generation of ammonia after exposure of the rat stomach to urea in the presence of urease, in attempts to investigate a pathophysiological role of urea, urease, and ammonia system in gastric ulcer diseases. Exposure of the stomach for 20 min to 2 ml urea (0.025-0.2%) together with urease (100 IU) induced histological damages in a concentration-related manner. Either urea or urease alone did not induce any histological change in the mucosa. Instillation of urea into the stomach generated ammonia in the presence of urease; the amount of ammonia was increased depending on the concentration of urea, and was closely associated with the severity of histological damage. The exposure of the stomach to ammonia (NH4OH: 0.01-0.1%) also produced histological damages in the gastric mucosa in a concentration-related manner. The characteristics of injury induced by 0.5-1.0% ammonia were stasis of microcirculation, disruption of the surface epithelial cells, and necrosis of the mucosa. These results demonstrated that ammonia generated from the hydrolysis of urea by urease in the stomach causes damages in the gastric mucosa.

Protective effect of taurine against ammonia-induced gastric mucosal lesions in rats.

We examined the role of gastric ammonia in the development of gastric lesions in rats. Exposure of the gastric mucosa to ammonia (30 mM) produced microscopic injury, but no macroscopic lesion was observed. However, exposure of the stomach to ammonia in rats subjected to ischemia resulted in macroscopic gastric lesions. The macroscopic lesions were markedly inhibited by pretreatment with taurine, a scavenger of hypochlorous acid (HOCI) and monochloramine (NH2Cl). These results indicate that ammonia is deleterious to gastric mucosa, and monochloramine may be involved in the pathogenesis of ammonia-induced mucosal lesions.

Cytoprotective effect of plasmin inhibitor on necrotizing agent-induced gastric lesions in rats.

We studied the effect of plasmin inhibitor on ethanol and ammonia-induced gastric mucosal lesions in rats using an ex vivo chamber. Tranexamic acid and aminocaproic acid significantly inhibited macroscopic gastric hemorrhagic necrosis and attenuated the decrease of gastric transmucosal potential difference induced by 50% ethanol and 1% ammonia. The protection of gastric mucosa afforded by tranexamic acid and aminocaproic acid was not affected by pretreatment with indomethacin (5 mg/kg). These results suggest that plasmin inhibitor plays an important role in the prevention of gastric deep necrosis following exposure of the stomach to a damaging agent.