Controllable vitamin K deficiency under high-dose oral menatetrenone administration - a case report.

Vitamin (V) K deficiency may cause severe bleeding tendencies, which necessitates extreme caution. We report a case of a 30-year-old man diagnosed with VK deficiency of unknown etiology. He was treated with intravenous menatetrenone three times a week in an outpatient setting for about 1 year and 9 months. Eventually, he developed an allergic reaction to intravenous menatetrenone and was under steroid therapy. In order to reduce his hospital visits and discontinue steroid use, the pharmacist proposed to change the method of menatetrenone administration from intravenous to oral (high dose). The change in treatment method has greatly improved the patient's quality of life.

Evaluation of sympathetic vasoconstrictor response following nociceptive stimulation of latent myofascial trigger points in humans.

AIM: Myofascial trigger points (MTrPs) are a major cause of musculoskeletal pain. It has been reported that stimulation of a latent MTrP increases motor activity and facilitates muscle pain via activation of the sympathetic nervous system. However, the magnitude of the sympathetic vasoconstrictor response following stimulation of MTrP has not been studied in healthy volunteers. The aims of this study were to (1) evaluate the magnitude of the vasoconstrictor response following a nociceptive stimulation (intramuscular glutamate) of MTrPs and a breath-hold manoeuvre (activation of sympathetic outflow) and (2) assess whether the vasoconstrictor response can be further modulated by combining a nociceptive stimulation of MTrPs and breath-hold. METHODS: Fourteen healthy subjects were recruited in this study. This study consisted of four sessions (normal breath group as control, breath-hold group, glutamate MTrP injection group and glutamate MTrP injection + breath-hold group). Skin blood flow and skin temperature in both forearms were measured with laser Doppler flowmetry and infrared thermography, respectively, in each session (before the treatment, during the treatment and after the treatment). RESULTS: Glutamate injection into MTrPs decreased skin temperature and blood flow in the peripheral area. The magnitudes of the reduction were comparable to those induced by the breath-hold manoeuvre, which has been used to induce sympathetic vasoconstrictor response. CONCLUSION: The combination of glutamate injection into latent MTrPs together with the breath-hold manoeuvre did not result in further decrease in skin temperature and blood flow, indicating that sympathetic vasoconstrictor activity is fully activated by nociceptive stimulation of MTrPs.

Mechanical assessment of effects of grape seed proanthocyanidins extract on tibial bone diaphysis in rats.

We studied the effects of grape seed proanthocyanidins extract (GSPE) given as a ratio of 3 mg in 100 g in a standard diet, on the tibial bone diaphysis in low-calcium fed rats. Measurements of bone density, mineral content, geometry, and bone strength using peripheral quantitative computed tomography (pQCT). Further, the whole tibia bones were tested for mechanical resistance using a material-testing machine, and mineral elements were also determined. Forty male Wistar rats, 5 weeks old, were divided into control (Co), low-calcium diet (LC), low-calcium diet . standard diet (LCS), and low-calcium diet . standard diet with supplementary GSPE (LCSG) groups. We found no significant differences in body weight among the 4 groups, whereas all of the bone parameters in LC were significantly lower than those in Co (p<0.01, except in periosteal perimeter (Peri) p<0.05). The cortical bone mineral content (CtBMC), cortical bone density (CtvBMD) and Peri in LCSG were significantly higher than those in LCS (p<0.01; p<0.01; p<0.05, respectively). All bone parameters in LCSG were significantly higher than those in LC (p<0.01, except in Peri, and stress strain index to reference axis x (xSSI) p<0.05)). In addition, Ca, P, and Zn contents in LCSG were significantly higher than those in LCS (p<0.01; p<0.01; p<0.05, respectively). Our results suggest that GSPE included in a diet mixture with calcium has a beneficial effect on bone formation and bone strength for the treatment of bone debility caused by a low level of calcium.

Effects of grape seed proanthocyanidins extract on rat mandibular condyle.

We investigated the effects of grape seed proanthocyanidins extract (GSPE) on bone formation by examining total and cortical bone mass, density, architecture, and strength non-invasively using mandibular condyles of Ca-restricted rats. Forty Wistar male rats, each 5 weeks old, were divided into control (C), low-Ca diet (LCaD), low-Ca diet-standard diet (LcaD x SD), and low-Ca diet x Estandard diet with supplementary GSPE (LcaD x SD+GSPE) groups. In LCaD x SD group, after the bone debility was induced by low-Ca diet, a standard diet therapy was given. In LCaD x SD+GSPE group, after the bone debility was induced by low-Ca diet, a standard diet therapy with supplementary GSPE was given. Each mandibular condyle was examined using peripheral quantitative computed tomography (pQCT). There were no significant inter-group differences in body weight seen throughout the experimental period. In LcaD x SD+GSPE, cortical bone cross-sectional area and mineral content were not significantly different from C, while bone mineral content was significantly higher in LcaD x SD+GSPE than in LcaD x SD. Cortical bone density of LcaD x SD+GSPE was not significantly different from that of C, however, that value in LCaD and LcaD x SD was significantly lower than that. The cross-sectional (bending) moment of inertia values in LcaD x SD+GSPE were the highest among all groups, though they did not differ significantly from those in C. Further, the cross-sectional (bending) Stress/Strain Index (SSI) values in LcaD x SD+GSPE were statistically similar to those in C, however, not significant higher than in LcaD x SD. These results suggest that GSPE treatment would increase both bone mass and bone strength on the rat mandibular condyles.

Japanese cedar pollen-specific interleukin-4 production develops immediately after the first exposure to pollens in infants with atopic dermatitis.

BACKGROUND: Japanese cedar pollens (JCPs) spread over most areas of Japan from February to April and cause pollenosis. While IgE synthesis against JCPs starts after age 1, it remains to be clarified when JCP-specific T helper cells acquire the ability to produce IL-4, a cytokine that induces IgE synthesis. OBJECTIVE: This study aimed to clarify when the sensitization of T cells to JCPs develops. METHODS: Peripheral blood mononuclear cells from 153 children with atopic dermatitis (AD) aged 0-15 years were stimulated with a standardized JCP allergen. As parameters of T cell responsiveness, lymphocyte proliferation and the production of IL-4 and IFN-gamma were measured. RESULTS: T cell responses against JCPs were negative before March in infants with AD who had never been exposed to JCPs or who were exposed for less than a month (nine, seven and nine subjects for lymphocyte proliferation, cytokine production and IgE synthesis, respectively). Lymphocyte proliferation distinctly increased in 67.6% (23/34) of infants with AD examined between March and June. JCP-specific IL-4 production was observed in 56.0% (14/25) of infants with AD examined between March and June. Correspondingly, a slight increase in the level of serum JCP-specific IgE antibody was seen in 17.2% (five of 29) of infants with AD examined between April and June. CONCLUSION: These results demonstrate that the sensitization of T cells to JCPs is effectively completed within a few months after the first exposure to JCPs.

Roles of major oligosaccharides on Cry j 1 in human immunoglobulin E and T cell responses.

BACKGROUND: We have demonstrated that carbohydrates in Cry j 1, the major allergen of Cryptomeria japonica pollen, play a major role in promoting Cry j 1-specific Th2 response. However, little is known as to whether the carbohydrates directly participate in allergic responses. OBJECTIVE: We sought to determine whether Cry j 1-related oligosaccharides function as IgE and/or T cell epitopes. In addition, the regulatory effect of Cry j 1-related oligosaccharide on Cry j 1-specific T cell responses was investigated. METHODS: Two monovalent oligosaccharides largely found on Cry j 1, Manalpha1-6(Manalpha1-3)(Xylbeta1-2)Manbeta1-4GlcNAcbeta1-4(Fucalpha1-3)GlcNAc (M3FX), and GlcNAcbeta1-2Manalpha1-6(GlcNAcbeta1-2Manalpha1-3)(Xylbeta1-2)Manbeta1-4GlcNAcbeta1-4(Fucalpha1-3)GlcNAc (GN2M3FX) were prepared. Manalpha1-2Manalpha1-6(Manalpha1-2Manalpha1-3)Manalpha1-6(Manalpha1-2Manalpha1-2Manalpha1-3)Manbeta1-4GlcNAcbeta1-4GlcNAc (M9A) was used as control. Competitive inhibition ELISA for Cry j 1-specific IgE was performed using these oligosaccharides as inhibitors. In addition, T cell lines specific for Cry j 1 or purified protein derivative of Mycobacterium tubecurosis (PPD) were established, and cellular responses against these oligosaccharides were investigated in the presence or absence of the respective antigens. RESULTS: Overall, neither M3FX nor GN2M3FX displayed inhibitory effect on the binding between IgE and Cry j 1. In addition, M3FX did not by itself stimulate Cry j 1 or PPD-specific T cells. However, M3FX significantly inhibited Cry j 1-induced proliferation and IL-4 production in Cry j 1-specific T cells. Such an inhibitory effect was not seen in PPD-specific T cell responses. CONCLUSION: These results suggest that Cry j 1-related oligosaccharides are not major epitopes for IgE or T cells. However, these oligosaccharides have a novel potential to inhibit Cry j 1-specific T cell responses selectively.

Effects of grape seed proanthocyanidins extract on mandibles in developing rats.

OBJECTIVE: Grape seed proanthocyanidins extract (GSPE), a flavonoid, has a beneficial effect on physical health, which may include the health of bone. The purpose of the present study was to investigate the effects of GSPE on mandibular bone by examining trabecular and cortical bone density, mineral content, and non-invasive bone strength in low-calcium diet rats. MATERIALS AND METHODS: Wistar male rats at 5 weeks old (n = 40) were divided into control (A), low-calcium diet (B), low-calcium diet plus standard diet (C), and low-calcium diet plus standard diet with supplementary GSPE (D) groups. Following 3 weeks of a calcium-restricted diet, group D rats were given 3 mg of GSPE as supplement in 100 g of a standard diet for the next 3 weeks. Following the 6-week experimental period, mandibular bones were examined using peripheral quantitative computed tomography (pQCT). RESULTS: There were no significant differences in body weight or trabecular bone area among the four groups. Trabecular bone density, and trabecular bone mineral content, cortical bone density, cortical bone cross-sectional area, and cortical bone mineral content were significantly higher in group D than in C. Further, Stress-strain index (SSI) values of xSSI and ySSI in group D were significantly higher than in C, although there was no significant difference in pSSI value between those two groups. CONCLUSION: Our results suggest that GSPE treatment caused an increase in both bone formation and bone strength in rat mandibles.

[Preoperative autologous blood donation in patients undergoing open heart surgery].

We examined the possibility to avoid the homologous blood transfusion in patients undergoing open heart surgery by predonation of 200 ml or 400 ml on the day before operation. Between March 1999 and December 2001, 117 patients underwent scheduled open heart surgery. In these patients, preoperatively collected autologous blood on the day before operation amounted 200 ml or 400 ml. We divided these patients into 3 groups according to the necessity of homologous blood, no transfusion (group A, n = 77), intraoperative transfusion (group B 1, n-29) and postoperative transfusion (group B 2, n = 11). In 65.8% of patients the homologous blood transfusion could be avoided. Preoperative, intraoperative and postoperative factors were compared in the 3 groups. Especially, old age, female, body weight and preoperative hemoglobin value were significantly different between 3 groups. Postoperative Svo2 and postoperative hemoglobin value were significantly different between 3 groups. The purpose of this study was to evaluate that the predonation of 200 ml or 400 ml on the day before operation may be to avoid the homologous blood transfusion and that preoperative, intraoperative and postoperative factors in regard to homologous blood transfusion.

Normalization of low biotinidase activity in a child with biotin deficiency after biotin supplementation.

We report findings in a Japanese boy with severe skin rash attributable to biotin deficiency. The patient had an intracranial malformation and developed biotin deficiency due to tube feeding with a single formula for over one year. Results of urinary organic acid analysis were consistent with multiple carboxylase deficiency, and low biotinidase activity was also observed. After biotin supplementation, the skin rash improved and biotinidase activity normalized. We speculate that biotin is one regulating factor in the biosynthesis of biotinidase.

The relation between single/double or repeated tea catechin ingestions and plasma antioxidant activity in humans.

OBJECTIVE: The purpose of this study was to investigate the effects of single/double or repeated intake of a normal amount of tea catechin on plasma catechin concentrations and antioxidant activity in young women. DESIGN: First, after an overnight fast, five healthy subjects were given water or single/double dose(s) of tea polyphenol extract (164 mg tea catechins containing 61% epigallocatechin gallate in 190 ml water). Blood samples were taken before and 30, 60 and 180 min after the ingestion. Second, 16 healthy subjects ingested the tea polyphenol extract three times a day at mealtimes for 7 days followed by withdrawal of tea polyphenol extract for 7 days. Blood samples were taken before and after ingestion, and 7 days after the withdrawal of tea catechin. Subjects were prohibited from drinking any beverages containing polyphenols or antioxidant supplements during the study period. Catechin and other antioxidant concentrations in the plasma were measured, and changes in antioxidant activity were evaluated by ferric reducing ability of plasma assay. RESULTS: Single/double ingestion of tea polyphenol extract did not cause an increase in the antioxidant activity. There was no also change in antioxidant activity after the ingestion of tea polyphenol extract for 7 days. Plasma-free epigallocatechin gallate concentration remained at the pre-study level; however, the plasma FRAP value decreased significantly at 7 days after the withdrawal of tea polyphenol extract. Decreases in endogenous antioxidants in the plasma, including vitamin C and bilirubin, were also observed 7 days after withdrawal of tea polyphenol. CONCLUSIONS: The results suggest that continuous daily intake of tea catechins affects the concentrations of endogenous antioxidants in the plasma and has the potential to maintain total antioxidant activity.

Effect of whole body hyperthermia on ischemia and reperfusion injury of rat intestine: real-time ATP change studied using (31)P-MRS.

We studied the effect of hyperthermia pretreatment on subsequent small intestinal ischemia and reperfusion (I/R) injury in the rat. Systemic hyperthermia has been reported to induce heat shock proteins (HSPs) in several organs [1-6]. We examined the expression of HSP72 in the small intestinal mucosa using Western blotting and immunohistochemistry. We monitored energy metabolism using magnetic resonance spectroscopy continuously during a 60-min ischemia and the following 120 min of reperfusion. Expression of HSP72 in the small intestine was significantly increased at 6-8 h after hyperthermia. Intestinal ischemia was induced by clamping the superior mesenteric artery. Heating of the rat conferred substantial resistance to the I/R injury. In the untreated rats, beta-ATP decreased during ischemia (37.1 +/- 15.5% of the pre-ischemic value) and recovered on reperfusion, but reached only approximately 50% of the pre-ischemic value after 120 min of reperfusion. However, beta-ATP in the pretreated rats was maintained during ischemia at significantly higher levels and on reperfusion reached approximately 80% of the pre-ischemic value. These results indicate that hyperthermia protects the rat intestine from the I/R injury by unknown mechanisms which may include the induction of HSPs.

N-linked oligosaccharides of glycoproteins from Ginkgo biloba pollen, an allergenic pollen.

The pollen of Ginkgo biloba is one of the allergens that cause pollen allergy symptoms. The plant complex type N-glycans bearing beta1-2 xylose and/or alpha1-3 fucose residue(s) linked to glycoallergens have been considered to be critical epitopes in various immune reactions. In this report, the structures of N-glycans of total glycoproteins prepared from Ginkgo biloba pollens were analyzed to confirm whether such plant complex type N-glycans occur in the pollen glycoproteins. The glycoproteins were extracted by SDS-Tris buffer. N-Glycans liberated from the pollen glycoprotein mixture by hydrazinolysis were labeled with 2-aminopyridine and the resulting pyridylaminated (PA-)N-glycans were purified by a combination of size-fractionation HPLC and reversed-phase HPLC. The structures of the PA-sugar chains were analyzed by a combination of two-dimensional sugar chain mapping, IS-MS, and MS/MS. The plant complex type structures (GlcNAc2Man3Xyl1Fuc1GlcNAc2 (31%), GlcNAc2Man3Xyl1GlcNAc2 (5%), Man3Xyl1Fuc1GlcNAc2 (13%), GlcNAc1Man3Xyl1Fuc1GlcNAc2 (8%), and GlcNAc1Man3Xyl1GlcNAc2 (17%)) have been found among the N-glycans of the glycoproteins of Ginkgo biloba pollen, which might be candidates for the epitopes involved in Ginkgo pollen allergy. The remaining 26% of the total pollen N-glycans have the typical high-mannose type structures: Man8GlcNAc2 (11%) and Man6GlcNAc2 (15%).

[A case of peculiar type of post-encephalitic/encephalopathic epilepsy: efficacy of bromide in the control of intractable seizures].

A 5-year-old boy with a peculiar type of post-encephalitic/encephalopathic epilepsy is reported. He had been healthy showing normal development before its onset. Five days after the onset of an upper respiratory infection, he had a severe generalized seizure, that evolved into intractable seizures. They were highly resistant to almost all anticonvulsants and occasionally resulted in status epilepticus. High-dose phenobarbital therapy successfully controlled the convulsions, but was discontinued because of drug-induced aplastic anemia. Alternative bromide therapy was markedly effective in controlling the seizures.

A new quantitative analytical method of serum biotinidase activity using biocytin as a substrate and its clinical significance in Japan.

We have developed a new quantitative analytical method of serum biotinidase activity, which uses the native substrate biocytin, and to which can be applied the improved agar plate method of biotin bioassay. Assay characteristics were within acceptable ranges (intra-assay CVs, 4.44% and 1.95% at 1.82+/-0.08 and 3.08+/-0.06 pmol/min/ml; day-to-day CV, 5.92% at 2.68+/-0.16 pmol/min/ml). The enzyme activity with biocytin was stable at 4 degrees C for 90 days. The mean value of the serum biotinidase levels in 129 healthy adults was 2.71+/-0.93 pmol/min/ml. The method was clinically comparable with a colorimetric method for detection of biotinidase deficiency. Biotin supplementation treatment normalized our partial biotinidase deficiency patient's serum biotinidase activity. This normalized phenomenon has not yet been observed in a Caucasian patient. We also found that the distribution of the enzyme activities with biotinyl-p-aminobenzoate in 8 of 11 patients with suspected biotin metabolic disorders shifted to a higher level than that of the controls. Although, we have few opportunities to analyze the sera of biotin metabolic disorders in Japan, the new method are suitable for clinical research applications in combination with the colorimetric method.

Neurons in the thalamic CM-Pf complex supply striatal neurons with information about behaviorally significant sensory events.

The projection from the thalamic centre médian-parafascicular (CM-Pf) complex to the caudate nucleus and putamen forms a massive striatal input system in primates. We examined the activity of 118 neurons in the CM and 62 neurons in the Pf nuclei of the thalamus and 310 tonically active neurons (TANs) in the striatum in awake behaving macaque monkeys and analyzed the effects of pharmacologic inactivation of the CM-Pf on the sensory responsiveness of the striatal TANs. A large proportion of CM and Pf neurons responded to visual (53%) and/or auditory beep (61%) or click (91%) stimuli presented in behavioral tasks, and many responded to unexpected auditory, visual, or somatosensory stimuli presented outside the task context. The neurons fell into two classes: those having short-latency facilitatory responses (SLF neurons, predominantly in the Pf) and those having long-latency facilitatory responses (LLF neurons, predominantly in the CM). Responses of both types of neuron appeared regardless of whether or not the sensory stimuli were associated with reward. These response characteristics of CM-Pf neurons sharply contrasted with those of TANs in the striatum, which under the same conditions responded preferentially to stimuli associated with reward. Many CM-Pf neurons responded to alerting stimuli such as unexpected handclaps and noises only for the first few times that they occurred; after that, the identical stimuli gradually became ineffective in evoking responses. Habituation of sensory responses was particularly common for the LLF neurons. Inactivation of neuronal activity in the CM and Pf by local infusion of the GABA(A) receptor agonist, muscimol, almost completely abolished the pause and rebound facilitatory responses of TANs in the striatum. Such injections also diminished behavioral responses to stimuli associated with reward. We suggest that neurons in the CM and Pf supply striatal neurons with information about behaviorally significant sensory events that can activate conditional responses of striatal neurons in combination with dopamine-mediated nigrostriatal inputs having motivational value.

Progression of T cell lineage restriction in the earliest subpopulation of murine adult thymus visualized by the expression of lck proximal promoter activity.

The proximal promoter of lck directs gene expression exclusively in T cells. To investigate the developmental regulation of the lck proximal promoter activity and its relationship to T cell lineage commitment, a green fluorescence protein (GFP) transgenic (Tg) mouse in which the GFP expression is under the control of the proximal promoter of lck was created. In the adult GFP-Tg mice, >90% of CD4(+)CD8(+) and CD4(+)CD8(-) thymocytes, and the majority of CD4(-)CD8(+) and CD4(-)CD8(-) [double-negative (DN)] thymocytes were highly positive for GFP. Slightly lower but substantial levels of expression of GFP was also observed in mature splenic T cells. No GFP(+) cells was detected in non-T lineage subsets, including mature and immature B cells, CD5(+) B cells, and NK cells, indicating a preserved tissue specificity of the promoter. The earliest GFP(+) cells detected were found in the CD44(+)CD25(-) DN thymocyte subpopulation. The developmental potential of GFP(-) and GFP(+) cells in the CD44(+)CD25(-) DN fraction was examined using in vitro culture systems. The generation of substantial numbers of alphabeta and gammadelta T cells as well as NK cells was demonstrated from both GFP(-) and GFP(+) cells. However, no development of B cells or dendritic cells was detected from GFP(+) CD44(+)CD25(-) DN thymocytes. These results suggest that the progenitors expressing lck proximal promoter activity in the CD44(+)CD25(-) DN thymocyte subset have lost most of the progenitor potential for the B and dendritic cell lineage. Thus, progression of T cell lineage restriction in the earliest thymic population can be visualized by lck proximal promoter activity, suggesting a potential role of Lck in the T cell lineage commitment.

Complete amino acid sequences of three proteinase inhibitors from white sword bean (Canavalia gladiata).

Three major serine proteinase inhibitors (SBI-1, -2, and -3) were purified from the seeds of white sword bean (Canavalia gladiata) by FPLC and reversed-phase HPLC. The sequences of these inhibitors were established by automatic Edman degradation and TOF-mass spectrometry. SBI-1, -2, and -3 consisted of 72, 73, and 75 amino acid residues, with molecular masses of 7806.5, 7919.8, and 8163.4, respectively. The sequences of SBI-1 and -2 coincided with those of CLT I and II [Terada et al. (1994) Biosci. Biotech. Biochem., 58, 376-379] except only N- or C-terminal amino acid residues. Analysis of the amino acid sequences showed that the active sites of the inhibitors contained a Lys21-Ser22 against trypsin and Leu48-Ser49 against chymotrypsin, respectively. Further, it became apparent that about seven disulfide bonds were present. These results suggest that sword bean inhibitors are members of the Bowman-Birk proteinase inhibitor family.

Appearance of peculiar vessels with immunohistological features of high endothelial venules in the dermis of moxibustion-stimulated rat skin.

Morphological changes of the dermal blood vessels ofmoxibustion-stimulated rat skin were examined with reference to the lymphocyte migration. After long-term stimulation with direct moxibustion to the acupoint tsu-san-li (St-36), peculiar vessels that possess immunohistological features of high endothelial venules could be observed in the moxa-stimulated acupoint dermis. Endothelial cells of the vessels had well-developed Golgi apparatus in their plump cytoplasms, and they strongly expressed intercellular adhesion molecule-1 on the luminal surface. These data suggest that the appearance of the peculiar vessels in the dermis acts toward the active infiltration of blood-lymphocytes into the acupoint skin.

Comparative assessment of the anxiolytic-like activities of honokiol and derivatives.

Honokiol has previously been shown to be an effective anxiolytic-like agent in mice when administered for 7 days at 0.2 mg/kg/day prior to evaluation in an elevated plus-maze, while 20 mg/kg is required for efficacy as a single oral dose. The aim of this study was to find analogs of honokiol that are more effective for acute administration. Among the eight analogs evaluated, one partially reduced derivative of honokiol [3'-(2-propenyl)-5-propyl-(1,1'-biphenyl)-2,4'-diol] exhibited significant anxiolytic-like activity at 0.04 mg/kg. Following oral administration of 1 mg/kg of this analog, anxiolytic-like activity was clearly evident at 1 h, peaked at 3 h, and remained significant for longer than 4 h after treatment. Combined administration of the derivative with diazepam led to enhanced anxiolytic-like efficacy. Moreover, as with diazepam, the anxiolytic-like effect of the analog was reduced by flumazenil. In contrast, bicuculline, a GABA(A) antagonist, had no effect on the activity of the derivative. Taken together, these results suggest that this analog of honokiol acts at the benzodiazepine recognition site of the GABA(A)-benzodiazepine receptor complex.

Double ventricular response by a single ventricular extrastimulus to the inner loop of reentry in a patient without apparent heart disease.

In a patient without apparent heart disease, a ventricular extrastimulus delivered from the left ventricular apex where the electrogram was recorded 30 ms after the onset of the QRS complex during VT advanced the second QRS complex, but not the first QRS complex. The morphology of the second QRS complex was the same as that of VT. The postpacing interval was the same as the cycle length of the VT. These findings indicated that the site of stimulation was at the inner loop of the reentry circuit of the VT. A ventricular extrastimulus with a shorter coupling interval advanced the first and second QRS complexes, indicating that the ventricle was activated by antidromic and orthodromic activation from the extrastimulus. Radiofrequency ablation at that site of stimulation terminated the VT and no further VT could be induced.