Acid-catalyzed cyclization of vinylsilanes bearing an amino group. Stereoselective synthesis of pyrrolidines

[reaction: see text] In the presence of an acid catalyst, vinylsilanes 1 bearing an amino group protected by an electron-withdrawing group were smoothly cyclized to 2-(silylmethyl)pyrrolidines 2. This cyclization was utilized for the stereoselective synthesis of 2,n-disubstituted pyrrolidines (n = 3-5). The cyclized products could be converted to the corresponding alcohols by oxidative cleavage of the carbon-silicon bond with TBAF and H2O2.

Portal-hepatic venous shunt through a portal aneurysm complicated by hepatic encephalopathy and pulmonary hypertension.

We report a rare case of portal-hepatic venous shunt through an enormous portal aneurysm complicated by pulmonary hypertension. A 66-year-old woman was admitted to our hospital for hepatic encephalopathy. Chest roentgenography revealed pulmonary hypertension. Computed tomography and ultrasound examination demonstrated a shunt between the portal and hepatic veins through an enormous portal aneurysm. The diagnoses of portal-hepatic venous shunt and pulmonary hypertension were confirmed by hepatic venous catheterization and cardiac catheterization. Pulmonary hypertension might result from the effects of vasoconstrictive agents, which should be metabolized by the liver in normal subjects, passing through the intrahepatic shunt into the lung.

Effects of volume loading on pulmonary venous flow and its relation to left atrial functions.

Although pulmonary venous (PV) flow is closely related to left atrial (LA) pressure dynamics, few investigators have discussed it in relation to LA functions, i.e., reservoir, conduit, and booster pump functions. We examined changes in PV flow rate, LA dimension, and left ventricular filling volume in 11 dogs, and assessed the effects of multistaged volume loading on PV flow and LA functions. Systolic PV flow rate (S) increased significantly and reached a plateau, reflecting a limited LA reservoir function. Diastolic PV flow rate (D) increased significantly with an increase in LA pressure. S/D ratio increased non-significantly from 0.87 +/- 0.07 before volume loading to 0.96 +/- 0.08 until S reached a plateau and then decreased to 0.76 +/- 0.08 (p < 0.05) because of a significant increase in D without an increase in S at the higher stages of volume loading. During atrial contraction, increases in LA active shortening and left ventricular filling volume were limited, indicating a limited LA forward ejection. The difference between PV flow rate just before and at the end of atrial contraction increased and correlated positively with left ventricular end-diastolic pressure (r = 0.57, p < 0.01). PV flow varies according to the degree of volume loading and reflects LA functions, which exhibit limited increases in response to volume loading.

Infection with Mycobacterium avium-intracellulare with abscess, ulceration and fistula formation.

Infections caused by Mycobacterium avium-intracellulare complex are generally manifested as pulmonary disease, osteomyelitis or lymphadenitis, and cutaneous infection is rare. We describe a case of M. intracellulare infection of the skin in a 79-year-old man without apparent immunologically disabling disease or therapy. He had cutaneous infection of the right hand over 10 years, developing a fistula and, finally, an ulcer and abscess, 2 months before his death from heart failure. Mycobacterium intracellulare was identified by both microbiological characteristics and DNA-DNA hybridization.

Adverse effects of interferon on the cardiovascular system in patients with chronic hepatitis C.

The therapeutic effects of interferon in chronic hepatitis C and many of its adverse effects have been well documented. However, there are only a few reports regarding its adverse effects on the cardiovascular system. The aim of this study was to clarify the clinical features of the adverse effects of interferon on the cardiovascular system in patients with chronic hepatitis C. We monitored 295 patients with chronic active hepatitis C during 312 courses of interferon therapy and for 1 year after the end of treatment for the presence of cardiovascular adverse effects. We found 6 patients with cardiovascular adverse effects during interferon therapy and 4 more patients within 1 year after the end of therapy (10/312, 3.2%). The adverse effects of interferon on the cardiovascular system included arrhythmia (n = 4), ischemic heart disease (n = 4) and myocardial disease (n = 2). None of the clinical factors, including history of cardiovascular disease, were related to these cardiovascular adverse effects. In all instances the patient's condition improved after discontinuation of interferon and adequate therapy. The cardiovascular adverse effects of interferon occurred frequently in patients with chronic hepatitis C, even after the end of therapy and they were unpredictable. Thus, all patients undergoing interferon therapy should be monitored not only during but also after the end of treatment.

Sarcoidosis after interferon therapy for chronic active hepatitis C.

Sarcoidosis is characterized by multisystemic granulomatous lesions of unknown etiology. A 62-year-old woman developed sarcoidosis after treatment with alpha-2a interferon (IFN) for 24 weeks (total dose: 522 million units) for chronic hepatitis C. She developed complete atrioventricular block and multiple noncaseating granulomatous lesions in the lung. IFN therapy, which may disturb cellular immune activation in some patients, may have contributed to the onset and progression of sarcoidosis.

Cardiogenic shock following recombinant alpha-2b interferon therapy for chronic hepatitis C. A case report.

A 57-year-old woman with chronic hepatitis C was treated with alpha-2b interferon (IFN). Forty-five days after the initiation of IFN therapy, she developed cardiogenic shock. Acute perimyocarditis as a cause of cardiogenic shock was clinically suspected by the findings of complete atrioventricular block, regional wall motion abnormality and pericardial effusion. Since IFN therapy may induce cardiogenic shock in some patients, it is important to carefully monitor patients under treatment with IFN for abnormal cardiac signs.

Effects of heart rate on left atrial contractile performance and left ventricular filling during atrial systole in dogs.

Left ventricular (LV) diastolic filling and left atrial (LA) contribution have been investigated in patients with heart disease. However, many of these studies were not conducted at a constant heart rate, and the effects of heart rate remain unclear. The purpose of this study was to clarify the effects of the heart rate on left atrial contractile performance and left ventricular filling during atrial systole. The changes in LA and LV dimensions and pulmonary venous (PV) flow were determined in 9 open-chest dogs by a sonomicrometer and an electromagnetic flowmeter. With a stepwise decrease in the pacing rate from 110 beats/minute to 70 beats/minute, the LA dimension just before atrial contraction increased from 21.4 +/- 0.6 mm to 23.1 +/- 0.7 mm (p < 0.01), and the LA systolic shortening increased from 1.6 +/- 0.1 mm to 2.1 +/- 0.1 mm (p < 0.01). However, the calculated LV filling volume during atrial systole decreased from 1.9 +/- 0.3 ml to 1.4 +/- 0.2 ml (p < 0.01). The PV flow during atrial systole was directed toward the LA, and the LA influx volume from PV decreased from 0.6 +/- 0.1 ml to 0.2 +/- 0.04 ml (p < 0.01). With a decrease in the pacing rate, the LA Frank-Starling mechanism operated. However, LV filling during atrial systole decreased because of the decrease in PV flow to the LV via the LA. Thus, LA contractile performance cannot always be evaluated from LV filling.

The role of the left atrial appendage. A volume loading study in open-chest dogs.

Although the left atrial appendage has a quite unique structure, its function remains unclear. To clarify the function of the left atrial appendage, changes in its anteroposterior, transverse and longitudinal dimensions, and in the anteroposterior dimension of the left atrial body were measured by a sonomicrometer during volume loading in open chest dogs. In the control state, fractional shortening of the transverse dimension of the appendage was greater than that of the atrial body. After dextran infusion, each dimension of the appendage and body, measured just before atrial contraction, increased curvilinearly. The percent increase in appendage dimensions was greater than that of the atrial body dimension (p < 0.05). Systolic shortenings of the appendage increased until mean left atrial pressure reached approximately 15 mmHg but after further pressure elevation, it decreased. In postmortem isolated hearts, the appendage volume was 17.2 +/- 4.4% of the whole left atrial volume. These findings indicate that the appendage has a considerable volume with a greater compliance and assists left ventricular filling during atrial contraction by a Frank-Starling mechanism.

Steroid sulfatase activities in human leukocytes: biochemical and clinical aspects.

Steroid sulfatase is a membrane-bound microsomal enzyme, present in various tissues. In this report, data on sulfatase activity in peripheral blood leukocytes isolated from normal women and the characterization of its enzyme are studied. In addition, sulfatase activities in placental sulfatase deficiency (PSD) and ichthyosis patients including ichthyosis vulgaris (IV) and recessive X-linked ichthyosis (RXLI) were analysed and were compared with normal subjects. Steroid sulfatase activity was measured by using tritium labeled steroid sulfate as the reaction substrate. It is demonstrated that human leukocytes contain a sulfatase activity for pregnenolone sulfate (P5-S), dehydroepiandrosterone sulfate (DHA-S) and estrone sulfate (E1-S) respectively. This enzyme has a greatest affinity for P5-S, but the activity for E1-S was the highest among the three substrates. The steroid sulfatase activity in female leukocytes is significantly stronger than that in normal males (p less than 0.001) as determined by the cleavage of DHA-S. Sulfatase in leukocytes obtained from the PSD babies and RXLI patients had lower sensitivity. In the case of the mother affected with PSD, the activity was less than half of that in normal men (p less than 0.001) and the levels did not overlap with that in normal women. In patients with IV, the activities were in the normal ranges for both males and females. The measurement of leukocyte sulfatase activity would be a clinically useful tool for the diagnosis of PSD carriers and pedigree analysis.

Effects of volume loading on left atrial systolic time intervals.

The effects of volume loading on the left atrial preejection period (LAPEP) and left atrial ejection time (LAET) were examined in 24 patients with various heart diseases using pulsed Doppler echocardiography. In response to volume loading, the left atrial dimension before atrial contraction significantly increased from 30.6 mm +/- 5.8 mm to 32.4 mm +/- 5.4 mm and the change in the left atrial dimension during atrial contraction tended to increase. The peak velocity in the atrial contraction phase significantly increased from 58 cm/s +/- 14 cm/s to 63 cm/s +/- 13 cm/s, and the integral of the atrial contraction phase tended to increase. LAPEP significantly decreased from 114 ms +/- 16 ms to 104 ms +/- 14 ms and LAET significantly decreased from 128 ms +/- 15 ms to 124 +/- 12 ms. The relation between LAET and left ventricular end-diastolic pressure, and that between LAPEP and mean pulmonary capillary wedge pressure, shifted downward to the right after volume loading. Thus, left atrial ejection is augmented by volume loading according to the Frank-Starling mechanism, while LAPEP decreases due to an increase in preload and LAET decreases due to an increase in afterload.

Determinants of left atrial systolic time intervals--assessment by pulsed Doppler echocardiography.

To evaluate the responsible factors for left atrial ejection, the left atrial preejection period (LAPEP), i.e., the time interval between atrial pacing pulse and onset of atrial ejection, and left atrial ejection time (LAET), i.e., the duration of atrial ejection, were determined from mitral inflow velocity patterns in 35 patients with various heart diseases using pulsed Doppler echocardiography. LAPEP ranged from 75 to 157 (mean 110 +/- 18) msec and LAET from 80 to 169 (mean 124 +/- 19) msec. The left atrial dimension before atrial contraction showed no significant correlation with LAPEP or LAET. Peak velocity during atrial contraction was negatively correlated with LAPEP (r = -0.42, p less than 0.05) and positively with LAET (r = 0.56, p less than 0.01). Left ventricular end-diastolic pressure (LVEDP) indicated a significant negative linear correlation with LAET (r = -0.44, p less than 0.05). LAPEP showed no significant linear correlation with LVEDP, but a significant curvilinear relationship was observed between them (LAPEP = 169 - 9.LVEDP + 0.28.LVEDP2, r = 0.63, p less than 0.001). Mean pulmonary capillary wedge pressure (mPCWP) was curvilinearly related to LAPEP (LAPEP = 168 - 11.mPCWP + 0.42.mPCWP2, r = 0.72, p less than 0.001) and LAET (111 + 4.1.mPCWP - 0.22.mPCWP2, r = 0.63, p less than 0.001). Although LAPEP decreased and LAET increased with increase in mPCWP up to about 15 mmHg, the reverse situation was noted for greater mPCWP. Thus, the major determinants of left atrial systolic time intervals are left atrial and ventricular pressures, and peak velocity during atrial contraction.

Efficacy and safety of catheter electrical ablation for ventricular tachycardia--experimental and clinical studies.

We studied the factors determining the extent of myocardial damage induced by catheter electrical ablation in 23 mongrel dogs and evaluated the efficacy and safety of catheter electrical ablation in 6 patients with medically refractory ventricular tachycardias (VT). Electrical shocks were delivered on the epicardium (EPI) and endocardium (END) of the ventricular wall of open-chest anesthetized dogs through a 6F USCI electrode catheter. Effect of the extent of electrode contact pressure was examined by the presence or absence of monophasic action potential using the contact electrode technique. The former was defined as the hard touch condition and the latter was defined as the soft touch condition. The myocardial lesion induced by EPI fulguration was larger than that by END fulguration (EPI-100 J soft touch: 10.2 +/- 2.9 mm in diameter, 6.6 +/- 1.6 mm in depth vs END-100 J soft touch: 7.7 +/- 1.7 mm in diameter, 5.0 +/- 1.2 mm in depth; p less than 0.05, p less than 0.05). The lesion diameter and lesion depth were enlarged by increasing the amount of delivered energy. The lesion depth by the hard touch condition was significantly greater than by the soft touch condition. The transmural perforation was observed in all EPI fulguration in the hard touch condition of the right ventricular wall. In the clinical study, one to three shocks (mean 1.8 +/- 0.7) of 60 to 200 J (mean 151 +/- 48 J) were delivered per session in 6 patients with medically refractory VT.(ABSTRACT TRUNCATED AT 250 WORDS)

[A study on tolerance to denopamine, oral beta 1-agonist].

To investigate whether effects of denopamine become weaker or not. Initial single dose (10 mg) effects, single dose effects after long-term treatment (30 mg per day, about 40 days), and chronic effects were studied by Doppler and echocardiography in 23 patients with heart failure (NYHA II-III). 1) Chronic effects: Blood pressure and heart rates didn't change significantly whether they were measured before or after long-term treatment. But left ventricular end-diastolic dimension decreased from 54.6 +/- 10.2 to 53.3 +/- 10.1 mm (p less than 0.01). Percent fractional shortening (%FS) increased from 22.6 +/- 7.8 to 25.3 +/- 8.6% (p less than 0.05). Mean velocity of circumferential fiber shortening (mVCF) tended to increase, and cardiac index (CI) increased from 2.71 +/- 0.47 to 2.98 +/- 0.57 l/min/m2 (p less than 0.01). 2) Initial single dose effects: Blood pressure and heart rates increased significantly. %FS increased from 25.0 +/- 7.7 to 25.9 +/- 7.8% (p less than 0.05), mVCF increased from 0.94 +/- 0.26 to 1.03 +/- 0.28 cir/sec (p less than 0.01), and CI increased from 2.81 +/- 0.49 to 3.09 +/- 0.49 l/min/m2 (p less than 0.01). 3) Single dose effects after long-term treatment: Blood pressure and heart rates increased significantly. %FS tended to increase, mVCF increased from 1.02 +/- 0.27 to 1.09 +/- 0.30 cir/sec (p less than 0.05), and CI increased from 3.05 +/- 0.62 to 3.37 +/- 0.54 l/min/m2 (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Assessment of supra-valvular abnormal signal with color Doppler flow mapping in patients with aortic regurgitation.

A supra-aortic abnormal flow signal (proximal acceleration) was studied in 62 patients with aortic regurgitation with the use of color Doppler flow mapping. The proximal acceleration signal was detected in 28 of the 62 patients and was shaped like a V or a teardrop. In the 29 patients who underwent aortography, a proximal acceleration signal was observed in all 18 patients with severe and moderate regurgitation and in only one of the 11 patients with mild regurgitation. The sensitivity for the diagnosis of severe regurgitation from the existence of a proximal acceleration signal was 100%, specificity 50%, and predictive accuracy 47%. A close correlation between the area of the proximal acceleration signal and the width of the aortic regurgitant jet signal was observed (r = 0.81). An acceleration area of 45 mm2 or more was observed in eight of the nine patients with severe regurgitation, in four of the nine patients with moderate regurgitation, and in none of the patients with mild regurgitation. Sensitivity for the diagnosis of severe regurgitation from an area of proximal acceleration of more than 45 mm2 was 89%, specificity 80%, and accuracy 67%. These results suggest that evaluation of the area of the supra-aortic abnormal signal may be a useful auxiliary aid in estimating the severity of aortic regurgitation.

[Secundum atrial septal defect in two families].

Two families having secundum atrial septal defect (ASD) were reported. In one family, a 31-year-old male and his 60-year-old mother had secundum ASD without PR prolongation. His 38-year-old brother was diagnosed as having ASD. His grandmother, who had died at the age of 51, was suspected of having congenital heart disease. From early childhood she was noticed to have heart murmur. It was suspected that this was a case of familial ASD without PR prolongation, because it was consistent with the dominant trait of the defect. In the other family, a 16-year-old female had secundum ASD and her 18-year-old brother was also suspected of having ASD. Her 25-year-old brother had been operated on for tetralogy of Fallot, and her sister had died of an unknown congenital heart disease. All of these family members had mental retardation. Her 22-year-old brother was suspected of having a congenital heart disease, because of heart murmur from his early childhood. The parents, who were blood relations (cousins), had neither heart disease nor mental retardation. The children of this family were considered to be cases of congenital heart disease with ASD, associated with mental retardation. It was also suspected that the cause of the defect was a deleterious autosomal recessive gene.

Automated identification of toxic substances in poisoned human fluids by a retention prediction system in reversed-phase liquid chromatography.

An automated identification system based on the retention prediction concept has been constructed for toxic substances. The system performance has been evaluated for the identification of toxic compounds in poisoned human fluids.

Quantitative deconvolution of heavily fused chromatographic peaks of biological components using a multi-wavelength UV detector.

Quantitative deconvolution of a chromatographic peak with extremely low UV absorption (less than 0.005 A.U.) is demonstrated for the analysis of an anaesthetic (ketamine) in rabbit serum. One ketamine metabolite, nor-ketamine, was deconvoluted from a completely fused peak in the three-dimensional chromatogram by using a highly sensitive multi-wavelength UV detector. After injection of ketamine, the nor-ketamine level in the serum increased to 3 micrograms/ml, calculated as ketamine, in 120 min.