Relationship between body mass index of offspring and maternal smoking during pregnancy.

OBJECTIVE: To examine the relationship between maternal smoking during pregnancy and the body composition of offspring. SUBJECTS: Grade 4 elementary school children (n=1366; boys/girls, 724/642; 9-10 years old) were enrolled in this study. All parents answered a lifestyle questionnaire, and children underwent passive smoking tests. Urinary cotinine measurement and lifestyle screening test parameters (that is, body weight, body length, body mass index (BMI), obesity index (OI), blood tests for liver function and lipid profile and questions regarding maternal smoking and lifestyle) were evaluated in terms of their relationship with maternal smoking. In addition, urinary 8-hydroxydeoxyguanosine (8-OHdG) concentration was measured in 80 randomly selected children to assess its relationship with oxidative stress. RESULTS: Both BMI and OI were significantly higher in children whose mothers smoked during pregnancy than in those whose mothers never smoked (BMI: 17.2±2.7 vs 16.9±2.5 kg m(-2), P=0.016; OI: 2.7±14.3% vs 0.4±14.0%, P=0.003). The degree of elevation was positively correlated with the duration of maternal smoking. The increases in BMI and OI resulted from increased body weight and reduced height. The confounding factors-'breakfast with family', 'watching television at dinner', 'eating and drinking before sleep', 'watching television for >2 h', 'sleep duration <8 h' and 'playing sports'-were statistically significant. BMI and OI were significantly high in children whose mothers smoked during pregnancy in these six confounders. On the other hand, urinary 8-OHdG concentration was negatively correlated with BMI in children who had >1.3 ng ml(-1) urinary cotinine, suggesting that it may be related to basal metabolism due to oxidative stress. CONCLUSION: Maternal smoking is a risk factor for higher BMI and OI in 9- to 10-year-old children whose mothers smoke during pregnancy and may be independent of other confounding factors.

[Effects of intra-coronary and intra-graft administration of nicorandil for coronary spasm after coronary artery bypass grafting].

Coronary artery spasm after coronary artery bypass grafting (CABG) is relatively rare, but when it occurs, it is fatal. In cases of circulatory collapse just after surgery, coronary spasm should be suspected, and immediate diagnosis by coronary angiography is necessary. We conducted a study to assess the clinical characteristics of coronary spasm after CABG and the usefulness of intra-coronary and intra-graft administration of nicorandil. Study subjects were 7 patients (6 men and 1 woman, mean age 60.4 years) in whom coronary spasm after CABG was diagnosed angiographically from January 1992 to December 2003. Off-pump CABG (OPCAB) had been performed in 2 patients. Despite continuous administration of nitroglycerin and diltiazem hydrochloride during surgery, sudden circulatory collapse occurred during surgery or within 24 hours after CABG in all 7 patients. All required mechanical circulatory support, and emergency coronary angiography revealed severe graft and native coronary spasms. Intracoronary and/or intra-graft administration of diltiazem hydrochloride or nitroglycerin was not very effective, however, administration of nicorandil was effective for vasodilatation. One patient suffered brain damage and died, but the other 6 patients recovered and were discharged without complication. In conclusion, intra-coronary and/or intra-graft administration of nicorandil appears to be useful for the treatment of coronary spasm after CABG.

Non-magnetic flexible heaters for spin-exchange optical pumping of 3He and other applications.

Spin polarized 3He gas is currently widely used in various scientific fields and in medical diagnosis applications. The spin polarization of 3He nuclei can be achieved by spin-exchange optical pumping (SEOP). In SEOP, the 3He gas is enclosed in a glass cell together with alkali metals and is then heated to maintain the alkali metal vapor pressures at the appropriate levels. However, polarized 3He gas is highly sensitive to any inhomogeneity in its magnetic field, and any small field gradients caused by the heaters may cause degradation of the 3He polarization. To overcome this conflict between the heating process and the magnetic field, we have developed electrical heaters that essentially cause no magnetic fields. These heaters are thin and are flexible enough to be bent to within a radius of a few centimeters. These carefully designed heater elements and a double layer structure effectively eliminate magnetic field generation. The heaters were originally developed for SEOP applications, but can also be applied to other processes that need to avoid unwanted magnetic fields.

Identification of a member of the TIS11 early response gene family at the insertion point of a DNA fragment containing a gene for the T-cell receptor beta chain in an acute T-cell leukemia.

In a previous paper (Proc. Natl. Acad. Sci. USA 84, 4264, 1987) we reported that a DNA fragment containing a gene for the T-cell receptor beta chain, which had been excised from chromosome 7q35 during D beta-J beta joining, was inserted into chromosome 6p21.3 in a patient with acute T-cell leukemia. We have since screened for genes in the vicinity of the insertion point and have identified a gene that is equivalent to the murine TIS11d gene, a member of TIS11 early response gene family, that contains unique Cysteine-Histidine motifs. The human TIS11d gene consists of two exons and encodes a polypeptide of 492 amino acids. The insertion of the DNA fragment observed in this patient is located at the carboxy-terminal portion of the TIS11d protein.

Cellular mechanisms of ventricular bipolar electrograms showing double and fractionated potentials.

OBJECTIVES: This study sought to determine the types of trans-membrane action potentials associated with bipolar electrograms that show double and fractionated potentials. BACKGROUND: The cellular correlates of ventricular bipolar electrograms showing double potentials and fractionated low amplitude potentials remain poorly defined. METHODS: A bipolar electrogram (1-cm interelectrode distance [6F, USCI]) and two transmembrane action potentials (within 1 mm of each pole) were recorded simultaneously in 12 isolated canine right ventricular endocardial preparations (2 x 1 cm, 2 mm thick). The long axis of the bipolar electrode was parallel to the long axis of the superficial endocardial fibers, and the recordings were made at 40 to 500 Hz. RESULTS: The following phenomena were associated with double potentials: 1) an increase in conduction time between the two poles of the bipole during a) the propagation of premature action potentials (7 of 12 tissues in 4 mmol/liter extracellular potassium ion concentration [K+]o); b) rapid pacing and premature stimuli (3 of 6 in 9 mmol/liter [K+]o); and c) the propagation of slow responses induced by barium chloride (4 mmol/liter). There was a positive correlation between conduction time (CT) and interspike interval (IPI) of the double potential (IPI [ms] = 0.5 x CT [ms] + 35) during early afterdepolarizations induced by barium chloride (4 mmol/liter) superfusion (three of six tissues). The following events were associated with fractionated electrograms: 1) propagation of induced graded responses (six tissues) in 4 mmol/liter [K+]o; 2) induced reentry at cycle lengths of 140 to 170 ms in 9 mmol/liter [K+]o (four of six tissues); and 3) asynchronous afterdepolarizations induced by 4 mmol/liter barium chloride (four of six tissues). CONCLUSIONS: Endocardial double potentials and fractionated electrograms seen on clinically used bipolar electrodes occur under conditions of slowed or discontinuous conduction and induced reentry and during asynchronous automatic firing initiated by afterdepolarizations. Caution must be exercised in interpreting such bipolar electrograms because more than one type of cellular action potential may cause these abnormal electrographic results.

Cardiac manifestations in disorders of fat and carnitine metabolism in infancy.

The prognosis of patients with cardiomyopathy associated with hypocarnitinemia is uncertain. Cardiac hemodynamics, histologic findings and response to oral L-carnitine therapy were retrospectively evaluated in 11 children with cardiomyopathy associated with abnormal carnitine metabolism. Three had systemic carnitine deficiency, two familial hypocarnitinemia with neutropenia, three transient neonatal hypocarnitinemia and three a carnitine insufficiency syndrome. Six had a hypertrophic and five a dilated cardiomyopathy. Hypotonia was present in seven (64%). The cardiothoracic ratio was greater than 0.60 in eight (73%). The most frequent abnormality on the electrocardiogram was ST-T wave inversion in the left precordial leads with various degrees of left ventricular hypertrophy. Echocardiographically, two patients with hypertrophic cardiomyopathy had decreased left ventricular function and two patients with dilated cardiomyopathy had increased thickness of the left ventricular wall. Histologic evaluation (two autopsies and one endomyocardial biopsy) revealed striking lipid accumulation within hypertrophied myocytes. Six of eight patients on carnitine replacement therapy had improvement echocardiographically during a 3 month to 2 year follow-up period. In summary, both hypertrophic and dilated cardiomyopathy can result from abnormal carnitine metabolism. The determination of plasma carnitine concentrations and fatty acid metabolism by-products should be performed in all patients with either form of cardiomyopathy of unknown etiology because carnitine supplementation may lead to improvement.

Selective perfusion of ischemic myocardium during coronary venous retroinjection: a study of the causative role of venoarterial and venoventricular pressure gradients.

Coronary venous retroinjection is often associated with preferential distribution of flow to ischemic myocardium. The purpose of this study was to define the mechanism of such retrodistribution of flow. In 24 anesthetized open chest dogs, Monastral blue dye (10 ml) was injected by way of a balloon catheter in the distal great cardiac vein as a marker for retrograde flow distribution. The injection rate (0.6 to 2.4 ml/s) was adjusted such that systolic pressure in the anterior interventricular vein ranged between 60 and 85 mm Hg. In 11 dogs with no ischemia and normal myocardial perfusion pressure (96 +/- 8 mm Hg), no myocardial staining occurred despite retrograde filling of epicardial veins. One minute after occlusion of the left anterior descending coronary artery, dye injections caused selective staining of the cyanotic area in 15 of 18 episodes, sparing the normal myocardium within the zone of retroperfused veins. In five dogs, with the arterial pressure less than 55 mm Hg, retroinjection resulted in homogeneous staining of all the myocardium drained by the retroperfused veins. Selective staining of the ischemic myocardium caused by retroinjection was associated with the following pressure gradients: during systole from the anterior interventricular vein to the occluded coronary artery, 31 to 58 mm Hg, and during diastole from the retroperfused veins to the left ventricular chamber, 9 to 28 mm Hg. There was no diastolic venoarterial gradient in the ischemic myocardium. In normal myocardium, retroinjection did not reverse the arteriovenous pressure gradient. In conclusion, retrograde flow is primarily directed to myocardium with low anterograde perfusion pressure. Selective retrograde penetration of acutely ischemic myocardium can thus be achieved by a mechanism consistent with the development of venoarterial and venoventricular pressure gradients.

Expression of P-glycoprotein in de novo acute myelogenous leukemia at initial diagnosis: results of molecular and functional assays, and correlation with treatment outcome.

We investigated the expression of P-glycoprotein (P-gp) in 52 adults with de novo acute myelogenous leukemia (AML) at the initial diagnosis. We tested 52 patients by flow cytometry using the MRK16 monoclonal antibody (MoAb). To investigate the phenotype for multidrug resistance, 41 of the patients were analyzed using rhodamine 123 (Rh123). We found that 14 (27%) of the 52 patients were positive for P-gp expression by MRK16 MoAb using a cutoff of 5% positive cells. There was a significant correlation between the results of the two analyses (p < 0.01). We suggest that flow cytometry using MRK16 MoAb is acceptable for use in detecting P-gp expression in clinical samples. Among the 52 patients, 43 (83%) obtained a complete remission (CR) and 45% of remitters were predicted to be alive and in a CR after 8 years. Although the rate of CR on the MRK16-positive patients was comparable to that of the MRK16-negative patients, the MRK16-positive patients were prone to relapse. We conclude that determination of P-gp expression of de novo AML at initial presentation did not significantly influence the outcome of treatment.

Detection of AML1/ETO fusion transcript as a tool for diagnosing t(8;21) positive acute myelogenous leukemia.

The nonrandom chromosomal translocation t(8;21)(q22;q22) can be found frequently in acute myelogenous leukemia with maturation (AML-M2). The breakpoint of this translocation has been cloned and characterized, and fusion transcript AML1/ETO has been identified. Reverse transcription polymerase chain reaction (RT-PCR) can be used to amplify the breakpoint site of AML1/ETO in t(8;21)-positive AML-M2 patients. The chimeric transcript can be detected in all 16 (100%) t(8;21)-positive AML-M2 patients. In all samples, the size of the amplified DNA fragments and pattern of restriction digest were identical, indicating that the t(8;21) translocation breakpoint occurs within a single intron of the AML1 and ETO genes. Interestingly, this fusion transcript was also detected in one of 13 AML-M2 patients without the t(8;21) translocation, indicating that a masked translocation involving chromosomes 8 and 21, exists in AML. Minimal residual disease was detected by semi-nested RT-PCR in all four patients tested, who had been in complete remission for 12, 15, 34, and 52 months, respectively. These results indicate that RT-PCR amplification of the AML1/ETO fusion transcript is a powerful tool for diagnosing and monitoring minimal residual disease in AML-M2 patients.

Proliferative effects of several hematopoietic growth factors on acute myelogenous leukemia cells and correlation with treatment outcome.

The response of human acute myelogenous leukemia (AML) cells to four different hematopoietic growth factors (granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-1 beta (IL-1beta), interleukin-3 (IL-3), and stem cell factor (SCF)) and the relationship of the proliferative response of the AML cells to treatment outcome were studied. Proliferative responses were analyzed in 79 patients with de novo AML and 19 patients with AML arising from myelodysplastic syndrome (MDS). In de novo AML, a positive proliferative response (stimulation index >2) was seen in 65 to 75% of cases. AML cells arising from MDS had a much higher incidence of proliferative response to each growth factor (79 to 90%) and a much higher level of 3H-TdR incorporation. The relationship to treatment outcome was evaluated in 79 patients with de novo AML. The patients whose leukemic cells had a positive proliferative response to any growth factor, especially IL-3 and SCF, had a poorer outcome, ie a lower complete remission (CR) rate, shorter CR duration, and shorter survival. The outcome was particularly poor in patients whose leukemic cells had proliferative responses to all four or any of the growth factors, compared to patients whose leukemic cells had no response. This increased response may be a marker of poor prognosis in patients with AML.

Induction therapy by frequent administration of doxorubicin with four other drugs, followed by intensive consolidation and maintenance therapy for adult acute lymphoblastic leukemia: the JALSG-ALL93 study.

In order to improve the disappointing prognosis of adult patients with acute lymphoblastic leukemia (ALL), we applied similar induction therapy as that used for acute myeloid leukemia (AML), ie frequent administration of doxorubicin (DOX). DOX 30 mg/m(2) was administered from days 1 to 3 and from days 8 to 10 together with vincristine, prednisolone, cyclophosphamide and L-asparaginase, followed by three courses of consolidation and four courses of intensification. From December 1993 to February 1997, 285 untreated adult patients with de novo ALL were entered. Of 263 evaluable patients (age 15 to 59; median 31), 205 (78%) obtained complete remission (CR). At a median follow-up period of 63 months, the predicted 6-year overall survival (OS) rate of all patients was 33%, and disease-free survival (DFS) rate of CR patients was 30%, respectively. By multivariate analysis, favorable prognostic factors for the achievement of CR were age <40 and WBC <50 000/microl; for longer OS were age <30 and WBC <30 000/microl; and for longer DFS of CR patients were FAB L1 and ALT <50 IU/l. Among 229 patients who had adequate cytogenetic data, 51 (22%) had Philadelphia (Ph) chromosome. Ph-negative chromosome was a common favorable prognostic factor for CR, longer OS and DFS. DFS was not different between early sequential intensification (n = 48) and intermittent intensification (n = 43) during the maintenance phase. Among CR patients under 40 years old, the 6-year survival was not different between the allocated related allo-BMT group (34 patients) and the allocated chemotherapy group (108 patients). However, among patients with Ph-positive ALL, the survival of patients who actually received allo-BMT was superior to that of patients who received chemotherapy (P = 0.046).

Analysis of genetic polymorphism in NQO1, GST-M1, GST-T1, and CYP3A4 in 469 Japanese patients with therapy-related leukemia/ myelodysplastic syndrome and de novo acute myeloid leukemia.

Several genetic polymorphisms in metabolic activation or detoxification enzymes have been associated with susceptibility to therapy-related leukemia and myelodysplastic leukemia (TRLIMDS). We analyzed gene polymorphisms of NAD(P)H:quinone oxidoreductase (NQOl), glutathione S-tranferase (GST)-MI and -TI, and CYP3A4, the enzymes of which are capable of metabolizing anticancer drugs, in 58 patients with TRL/MDS and in 411 patients with de novo acute myeloid leukemia (AML). Homozygous Ser/Ser genotype of NQOl at codon 187, causing loss of function, was more frequent in the patients with TRLIMDS (14 of 58, 24.1%; OR = 2.62) than in those with de novo AML (64 of 411, 15.6%), and control (16 of 150, 10.6%; P = 0.002). Allelic frequencies of NQOJ were different between TRL/ MDS and de novo AML (P = 0.01). In GST-MJ and -Ti, the incidence of homologous deletion was similar among the three groups. The polymorphism of the 5' promoter region of CYP3A4 was not found in persons of Japanese ethnicity. These results suggest that the NQOJ polymorphism is significantly associated with the genetic risk of TRLIMDS.

A Ramsey's Method With Pulsed Neutrons for a T-Violation Experiment.

A Ramsey's method with pulsed neutrons is discussed for neutron spin manipulation in a time reversal (T) symmetry violation experiment. The neutron spin (s n) is aligned to the direction of a vector product of the nuclear spin ( I ) and the neutron momentum ( k n) for the measurement of a T-odd correlation term, which is represented as s n · ( k n × I ), during propagation through a polarized nuclear target. The phase control and amplitude modulation of separated oscillatory fields are discussed for the measurement of the T-odd correlation term.

Measurement of Parity Violation in np Capture: the NPDGamma Experiment.

The NPDGamma experiment will measure the parity-violating directional gamma ray asymmetry A γ in the reaction [Formula: see text]. Ultimately, this will constitute the first measurement in the neutron-proton system that is sensitive enough to challenge modern theories of nuclear parity violation, providing a theoretically clean determination of the weak pion-nucleon coupling. A new beam-line at the Los Alamos Neutron Science Center (LANSCE) delivers pulsed cold neutrons to the apparatus, where they are polarized by transmission through a large volume polarized (3)He spin filter and captured in a liquid para-hydrogen target. The 2.2 MeV gamma rays from the capture reaction are detected in an array of CsI(Tl) scintillators read out by vacuum photodiodes operated in current mode. We will complete commissioning of the apparatus and carry out a first measurement at LANSCE in 2004-05, which would provide a statistics-limited result for A γ accurate to a standard uncertainty of ±5 × 10(-8) level or better, improving on existing measurements in the neutron-proton system by a factor of 4. Plans to move the experiment to a reactor facility, where the greater flux would enable us to make a measurement with a standard uncertainty of ±1 × 10(-8), are actively being pursued for the longer term.

Commissioning of the NPDGamma Detector Array: Counting Statistics in Current Mode Operation and Parity Violation in the Capture of Cold Neutrons on B 4 C and (27) Al.

The NPDGamma γ-ray detector has been built to measure, with high accuracy, the size of the small parity-violating asymmetry in the angular distribution of gamma rays from the capture of polarized cold neutrons by protons. The high cold neutron flux at the Los Alamos Neutron Scattering Center (LANSCE) spallation neutron source and control of systematic errors require the use of current mode detection with vacuum photodiodes and low-noise solid-state preamplifiers. We show that the detector array operates at counting statistics and that the asymmetries due to B4C and (27)Al are zero to with- in 2 × 10(-6) and 7 × 10(-7), respectively. Boron and aluminum are used throughout the experiment. The results presented here are preliminary.

[Papillary fibroelastoma of the right atrium; report of a case].

Papillary fibroelastoma is a rare benign tumor commonly arising from a heart valve. We describe an unusual papillary fibroelastoma that arose from the right side of the interatrial septum. An intracardiac tumor was discovered by routine echocardiography in an asymptomatic 68-year-old woman. The echocardiographic examination revealed a 20 mm mobile tumor in the right atrium. Tricuspid obstruction was not observed, nor was regurgitation. The tumor was resected through a right atriotomy. It had multiple papillary fronds and arose from the interatrial septum. Pathologic examination confirmed papillary fibroelastoma. The postoperative course was uneventful, and the patient was discharged on postoperative day 13.

Relation of monophasic action potential recorded with contact electrode to underlying transmembrane action potential properties in isolated cardiac tissues: a systematic microelectrode validation study.

Monophasic action potentials, recorded with contact non-suction electrodes, have been used both clinically and experimentally. However, to date no systematic microelectrode validation studies have been done to underlying myocardial cell populations from different myocardial regions with different transmembrane potential profiles. In the present study transmembrane action potential properties, recorded with standard microelectrodes, were compared with monophasic action potentials recorded with contact electrodes in three different (endocardium, epicardium, and free running Purkinje fibre) isolated canine preparations during pacing and during spontaneous automatic activity. The mean transmembrane durations at 50% and 90% repolarisations (APD50 and APD90) of 19-30 cells at a monophasic action potential recording site was not statistically significant from monophasic action potential duration in all three tissue preparations studied. However, in endocardial preparations, composed of superficial (1-2 cell layers) Purkinje fibres with deeper ventricular muscle cells, the APD50 (139(17) ms) and APD90 (181(26) ms) of monophasic action potentials more closely reflected (but not significantly different) the underlying deeper ventricular muscle cells (APD50 134(14) ms and APD90 167(15) ms) rather than the mean transmembrane action potential durations of the underlying most superficial Purkinje fibres (166(22) ms for APD50 and 210(30) ms for APD90) (p less than 0.025). Tetrodotoxin (TTX) at 1 x 10(-6) mol.litre-1 shortened Purkinje fibre action potential duration and slightly lengthened that of ventricular muscle. Simultaneously recorded monophasic action potential showed an intermediate change in action potential duration. Incremental pacing and applied single premature stimuli resulted in similar degrees of shortening of action potential duration for both monophasic action potential and transmembrane potential in all three preparations. In endocardial preparations, barium chloride (4 mmol.litre-1) superfusion induced early afterdepolarisations, and spontaneous phase 4 depolarisations (n = 6) in both Purkinje and ventricular muscle cells giving rise to spontaneous automatic activity. These abnormal automatic activities were accurately detected by simultaneous monophasic action potential recordings. Suppression of automaticity by verapamil (0.2-0.5 micrograms.ml-1) as confirmed by transmembrane action potential recordings were similarly detected by monophasic action potential recordings (ABSTRACT TRUNCATED AT 250 WORDS)

Late persistent expressions of ICAM-1 and VCAM-1 on myocardial tissue in children with lymphocytic myocarditis.

BACKGROUND: Both intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) have been implicated in cardiac allograft rejection. However, there is little information about the relationship between the expression of these adhesion molecules and myocarditis in children. METHODS AND RESULTS: Immunoreactivities of ICAM-1 and VCAM-1 were examined by enzyme immunoassay in 31 biopsy specimens obtained from 11 pediatric patients with biopsy-proven myocarditis or cardiomyopathy. Five of the 11 patients had clear evidence of acute myocarditis. The other 6 had ECG abnormalities identified by mass screening for heart disease, and subsequently had been histologically diagnosed as having non-specific cardiomyopathy. The period between onset of myocarditis or identification of ECG abnormality and immunohistochemical studies was 23 to 60 days and 8 months to 3 years, respectively. Expression of ICAM-1 and VCAM-1 was assessed by counting ICAM-1 and VCAM-1 positive vessels and dividing by the total number of vessels. ICAM-1 was significantly present on 81% (P < 0.01) of myocardial tissue samples in the 5 patients with healing-stage acute myocarditis, and on 45% (P < 0.05) in the remaining 6 patients with non-specific cardiomyopathy, compared with 24% in control specimens obtained from right ventricular muscle resected at surgery for tetralogy of Fallot. VCAM-1 was also present on 50% (P < 0.05) of the samples from the 5 patients with acute myocarditis, but was not present in those with non-specific cardiomyopathy. CONCLUSION: This persistent expression of ICAM-1 suggests that myocardial cell damage may persist immunologically for a long period in myocarditis. In addition, immunostaining for these adhesion molecules may be diagnostic value in clinically silent lymphocytic myocarditis and chronic cardiomyopathy.

Pharmacokinetics of landiolol hydrochloride, a new ultra-short-acting beta-blocker, in patients with cardiac arrhythmias.

OBJECTIVES: To elucidate pharmacokinetics and pharmacodynamics of landiolol hydrochloride, newer developed ultra-short-acting beta-blocker, in patients with various cardiac tachyarrhythmias. BACKGROUND: The short duration of action and titratability of landiolol hydrochloride make it ideal for use in patients with a clinical need for beta-blockers. METHODS: In a total of 31 examinations we infused the drug in 19 patients (mean age, 55 +/- 14 years). After the persistence of the tachyarrhythmias was confirmed, continuous infusion was started at rates of 0.005, 0.01, 0.02, 0.04, and 0.08 mg/kg/min for 5 minutes (for paroxysmal atrial fibrillation, paroxysmal supraventricular tachycardia, and ventricular tachycardia) or 15 minutes (for ventricular premature complex). We analyzed the pharmacokinetics of 16 examinations. A one-compartment model provided a close fit for each blood concentration-time curve. RESULTS: The maximum blood concentrations obtained clearly showed the dose dependency and revealed very short half-lives (range, 2.3 to 4.0 minutes). Area under the blood concentration-time curves also increased, showing dose dependency. In paroxysmal atrial fibrillation, landiolol hydrochloride reduced the heart rate from 111 +/- 20 to 90 +/- 10/min. Sinus rhythm was restored, without any adverse effects, in three of five patients with paroxysmal supraventricular tachycardia and one patient with ventricular tachycardia. There was no significant change in peripheral blood pressure. CONCLUSIONS: Landiolol hydrochloride has a shorter elimination half-life than any other beta-blocker, and it can be administered safely to patients with various tachyarrhythmias.

Cingulate gyrus of the cat receives projection fibers from the thalamic region ventral to the ventral border of the ventrobasal complex.

Direct projections to the cingulate gyrus from the thalamic region lying just ventrally to the ventral border of the ventrobasal complex (VB) were found in the cat by two sets of experiments that used WGA-HRP (wheat germ agglutinin-horseradish peroxidase conjugate). In the first set of experiments, WGA-HRP was injected into the thalamic region around the ventral border of the VB. When the site of injection involved the thalamic region lying ventrally to the ventral border of the VB at the levels of the caudal two thirds of the VB, the cerebral cortex in the rostral part of the cingulate gyrus ipsilateral to the WGA-HRP injection contained fine HRP-positive granules, which indicated anterograde labeling of axon terminals. These labeled presumed axon terminals were mainly distributed to the superficial part of layer I, deep part of layer II, layer IV, and the most superficial part of layer V in the cingulate cortex. In the second set of experiments, WGA-HRP was injected into the cerebral cortex of the rostral part of the cingulate gyrus. When the site of injection involved the region of the cingulate gyrus, where presumed axon terminals had been labeled in the first set of experiments, the thalamic region just ventral to the ventral margin of the caudal two-thirds of the VB ipsilateral to the WGA-HRP injection contained neuronal cell bodies labeled retrogradely. The results indicate that some neurons that are located in the thalamic region just ventral to the ventral border of the caudal two-thirds of the VB send their axons to the cerebral cortex in the rostral part of the cingulate gyrus. The possible significance of the thalamocingulate projection found in the present study is discussed with relation to nociceptive behavior and function.