[Repair of tetralogy of Fallot with obstruction of right pulmonary artery; report of a case].

Patients with tetralogy of Fallot showing unilateral obstruction of a pulmonary artery, especially the right pulmonary artery, are a high-risk group for pulmonary hypertension after repair. This case of tetralogy of Fallot with the obstruction of the right pulmonary artery received a Blalock-Taussig shunt at 7 months old, and the occluded right pulmonary artery caused empyema after surgery. At 2 years old, a cardiac catheter study showed a pulmonary artery index of 193.6 mm2/m2, so we undertook intracardiac repair. After the repair, she showed a relativery favorable clinical course. Systolic pulmonary artery pressure and right ventricular pressure were about 30 and 50 mmHg, respectively. We considered that tetralogy of Fallot with obstruction of right pulmonary artery could be repaired, as long as the pulmonary artery index was within the limits of indication and the left ventricle was well-developed.

[Primary cardiac angiosarcoma in the left atrium with adrenal metastasis; report of a case].

We encountered a 61-year-old woman with primary cardiac angiosarcoma in the left atrium. On echocardiography, the tumor extended into the atrial septum and mitral valve, and mitral valve stenosis and regurgitation were significant. We resected the tumor protruding into left atrium, and affecting mitral valve. The surgical procedure was not radical, but on postoperative echocardiography, function of the mitral valve was improved. Three months later, elevation of her right diaphragma was observed on chest X-ray and a giant adrenal tumor was detected by magnetic resonance imaging. Tumor biopsy indicated that this tumor was adrenal metastasis from cardiac angiosarcoma. In addition, echocardiography showed the recurrence of angiosarcoma in the left atrium and the presence of mitral stenosis and regurgitation. She died of heart failure 185 days postoperatively.

Insertion of bacteriophage phiFSW into the chromosome of Lactobacillus casei strain Shirota (S-1): characterization of the attachment sites and the integrase gene.

The integrase gene (int) on the genome of φFSW, which is a temperate bacteriophage of Lactobacillus casei strain Shirota (formerly denoted as S-1), and the four attachment sites on the genomes of the phage and its host were characterized by sequencing. The φFSW integrase was found to belong to the integrase family of site-specific tyrosine recombinase. The attachment sites shared a 40bp common core within which an integrative site-specific recombination occurs. The common core was flanked on one side by an additional segment of high sequence similarity. An integration plasmid, consisting of int, the phage attachment site (attP), and a selectable marker, inserted stably into the bacterial attachment site (attB) within the common core, as did the complete prophage genome at a frequency of more than 10(3)/microg of plasmid DNA. This plasmid was used as a test system for a preliminary mutational analysis of int and attP. The attB common core was located within and near the end of an open reading frame that appears to encode a homolog to glucose 6-phosphate isomerase, an enzyme of the glycolytic pathway. It is unlikely that the prophage integration inactivates this protein, since a change of only the C-terminal amino acid is predicted because of the sequence similarity between attP and attB.

Right ventricular responses to vagus stimulation of fibers to discrete cardiac regions in dog hearts.

To investigate the role on the right ventricular function of the parasympathetic nerves in discrete cardiac regions, we studied the effects of stimulation of the intracardiac parasympathetic nerves to the atrioventricular (AV) nodal area (AVPS) or sinoatrial (SA) nodal area (SAPS), and stimulation of the cervical vagus nerves (CVS) on the right atrial and ventricular function in the autonomically decentralized heart of the anesthetized dog. AVPS prolonged AV conduction time (AVCT) and decreased the ventricular rate without changes in atrial rate, right atrial 'a' wave pressure (RAP), its first derivative (RAd P/dt), right ventricular pressure (RVP) and its first derivative (RVd P/dt) in the spontaneously beating heart. On the other hand, AVPS prolonged the AVCT in the atrium paced electrically and further decreased the ventricular rate with decreases in ventricular pressure responses but not atrial responses. SAPS decreased atrial and ventricular rates without AVCT changes and attenuated the right atrial and ventricular pressure responses. In the atrial paced heart, SAPS decreased the ventricular responses less than those responses in the spontaneously beating heart with similar decreases in the atrial pressure responses, but it changed neither the AVCT nor ventricular rate. On the other hand, CVS decreased the atrial and ventricular rate or pressure responses, and increased the AVCT. CVS in the paced heart also decreased the atrial and ventricular pressure responses with the prolongation of AVCT. The cardiac responses to parasympathetic stimulations were abolished by atropine. These results suggest that AVPS decreases ventricular rate without direct right ventricular pressure effects but the negative chronotropic effects of AVPS and SAPS decrease the ventricular pressure responses rate-dependently in the dog heart.

[A study of ceftriaxone concentration in serum and tissue of patients with chronic sinusitis].

After an intravenous drip infusion of 1 g or 2 g of ceftriaxone (CTRX), its concentrations in serum and tissue were determined using the bioassay for 18 surgical patients with chronic paranasal sinusitis. 1. The serum levels observed at 75-105, 135-165, 195-225 minutes after an intravenous drip infusion of 1 g, averaged 98 +/- 38, 92 +/- 13 and 73 +/- 13 micrograms/ml, respectively. 2. The tissue levels at 75-105, 135-165, 195-225 minutes after an intravenous drip infusion of 1 g, averaged 27 +/- 13, 27 +/- 7 and 25 +/- 9 micrograms/g. 3. CTRX appears to be a useful drug for the treatment of chronic paranasal sinusitis.

Are negative chronotropic and inotropic responses to adenosine differentiated at the receptor or postreceptor levels in isolated dog hearts?

Inhibition by zatebradine, a specific bradycardic agent, of the negative inotropic but not chronotropic responses to adenosine has been briefly reported in the isolated, perfused dog heart. We therefore investigated whether subtypes of adenosine receptors or postreceptor transduction mechanisms differentiated the negative chronotropic and inotropic responses to adenosine in the isolated, blood-perfused atrial and ventricular preparations of the dog. Adenosine (1-3000 nmol), adenosine A1 receptor agonists, 2-chloroadenosine (CAD, 0.1-300 nmol) and N6-cyclohexyladenosine (CHA, 1-300 nmol) and a nonselective adenosine receptor agonist, 5'-N-ethyl-carboxamidoadenosine (NECA, 0.1-100 nmol), induced the negative chronotropic and inotropic responses. The potency order was NECA > CAD > adenosine > or = CHA. An adenosine A1 receptor antagonist, 1,3-dipropyl-8-cyclopentylxanthine (DPCPX, 10-300 nmol), dose-dependently inhibited the negative chronotropic and inotropic responses to adenosine, CAD and NECA in the isolated, perfused right atrium. DPCPX also blocked the negative inotropic responses to adenosine, CAD and NECA in the isolated left ventricle. However, an adenosine A2 receptor antagonist, 3,7-dimethyl-1-propargylxanthine (DMPX, 300 nmol), did not affect the negative cardiac responses to adenosine and NECA. Although the negative inotropic but not chronotropic responses to CAD and adenosine were dose-dependently inhibited by zatebradine, K+ channel inhibitors 4-aminopyridine and E-4031 did not modify the cardiac responses to adenosine and CAD. These results suggest that the negative cardiac responses to adenosine are mediated by adenosine A1 receptors and the negative chronotropic and inotropic responses to adenosine are differentiated at the postreceptor transduction level(s) in the dog heart.

Zatebradine attenuates cyclic AMP-related positive chronotropic but not inotropic responses in isolated, perfused right atria of the dog.

1. Inhibition of I(f) or ICa by zatebradine has been reported in mammalian SA nodal cells. We thus investigated whether zatebradine differentially attenuates the positive chronotropic and inotropic responses to norepinephrine, isoproterenol, NKH 477 (an adenylyl cyclase activator), 3-isobutyl-1-methylxanthine (IBMX) and Bay k 8644 (a calcium channel agonist) in the isolated, blood-perfused dog atrium. 2. When zatebradine (0.03-1 mumol) decreased sinus rate from 104 +/- 4.5 to 73 +/- 4.9 beats/min dose-dependently, it selectively attenuated the positive chronotropic but not inotropic responses to norepinephrine in a dose-related manner. Zatebradine decreased the norepinephrine-induced tachycardia (by approximately 80% from the control) more effectively than the spontaneous sinus rate (by approximately 30% from the control). 3. Zatebradine similarly attenuated the positive chronotropic but not inotropic responses to isoproterenol, NKH 477 and IBMX. Fifty per cent inhibition doses of zatebradine (0.10-0.18 mumol) for the chronotropic responses to each substance were not significantly different. 4. On the other hand, zatebradine attenuated neither positive chronotropic nor inotropic responses to Bay k 8644. 5. We therefore suggest that zatebradine selectively attenuates the positive chronotropic but not inotropic responses to cyclic AMP-related substances due to inhibition of I(f) but not ICa in the dog heart.

Sinusitis associated with disorders of visual acuity.

We report a case of sinusitis associated with disorders of visual acuity. The patient's vision was dramatically improved by sinus surgery despite the fact that the changes in the ethmoidal cells were slight and had no direct observable relation to the optic nerve canal. Possible mechanisms involved in nasal optic neuritis are discussed.

Clinical efficacy of recombinant human granulocyte colony-stimulating factor in patients with head and neck cancer.

Recombinant human granulocyte colony-stimulating factor (rG-CSF) was used for the amelioration of neutropenia caused by cisplatin-based chemotherapy in head and neck cancer patients. For a dose-finding study of rG-CSF, 11 patients, who had levels of absolute neutrophil counts below 500/mm3 in peripheral blood, were administered rG-CSF subcutaneously at a dose of 1 or 2 micrograms/kg for 5 days. A 'useful' rate in 1 and 2 micrograms/kg was obtained in 71.4 and 100% of patients, respectively. In 6 patients, the clinical utility of rG-CSF at a dosage of 2 micrograms/kg from the day after chemotherapy for 10 consecutive days was observed. The percentage of 'very useful' evaluations was 83.3% (5/6). No side effects or abnormal laboratory findings were observed in any patients after administration of rG-CSF.

Parasympathetic control of right atrial pressure in anesthetized dogs.

We investigated whether the intracardiac parasympathetic ganglia for sinoatrial (SA) nodal pacemaker cells control the right atrial contractility selectively and totally in the autonomically decentralized heart of the open-chest anesthetized dog. Stimulation of the intracardiac parasympathetic nerves to the SA nodal area (SAP Stim) decreased the right atrial pressure (a wave pressure) and its first pressure derivative (dP/dt) as well as the atrial rate but did not change the atrioventricular (AV) conduction time. Stimulation of right and left cervical vagosympathetic complexes (CV Stim) decreased the a wave pressure, dP/dt, and atrial rate and prolonged the AV conduction time. When SAP and CV Stim decreased the atrial rate similarly, the decreases in a wave pressure and dP/dt in response to SAP Stim were less than those to CV Stim in unpaced and paced hearts. When treatment with hexamethonium bromide or tetrodotoxin into the SAP Stim locus abolished the decreases in atrial rate evoked by SAP and CV Stim, each treatment abolished the decrease in a wave pressure response to SAP Stim but only slightly attenuated the pressure response to CV Stim. These results demonstrate that right atrial pressure is modified by efferent parasympathetic neurons, which are located in a region that differs from that of efferent parasympathetic neurons controlling heart rate.

Selective inhibition by E4080, a novel bradycardic agent, of positive chronotropic responses to norepinephrine in isolated dog hearts.

E4080, a novel bradycardic agent acts on various ionic currents including the hyperpolarization-activated inward current (I(f)), L-type Ca2+ current (ICa) and ATP-sensitive K+ (K+ATP) current in mammalian heart and vascular tissues. We thus investigated the chronotropic and inotropic effects of E4080 and its interaction with the positive cardiac responses to norepinephrine, 3-isobutyl-1-methyl-xanthine (IBMX) and Bay k 8644 in the isolated, blood-perfused dog right atria and left ventricles. E4080 (0.01-1 mumol) decreased the sinus rate and atrial and ventricular contractile forces in a dose-related manner. Glibenclamide (3 mumol) partly blocked the decrease in atrial force but not the decreases in sinus rate and ventricular force induced by E4080. Atropine (10 nmol) did not affect the negative cardiac responses to E4080. E4080 (0.01-1 mumol) inhibited the positive chronotropic responses to norepinephrine and IBMX dose dependently, but did not inhibit the positive inotropic ones in isolated atria. E4080 affected neither positive chronotropic nor inotropic responses to Bay k 8644. These results suggest that (1) the activation of K+ATP channels by E4080 is partly related to the decrease in atrial force but not the decreases in sinus rate and ventricular force, and (2) the selective inhibition of E4080 of the cyclic AMP-dependent positive chronotropic responses but not inotropic ones is probably due to the inhibition of I(f) rather than other properties, e.g., activation of K+ATP channels and inhibition of ICa in the dog heart.

Tumours metastasizing to the head and neck--a report of seven cases.

Metastatic tumours involving the head and neck region are rare. Over the past 18 years, seven such cases were treated at our clinic. Of those, four were in one of the paranasal sinuses, three had arisen from a primary hepatocellular carcinoma and one from an osteogenic fibrosarcoma of the leg. In the remaining three cases, metastases to the larynx, the tonsil, and the parotid gland arose from a primary renal cell carcinoma, a thyroid carcinoma, and a breast carcinoma, respectively. In metastatic tumours, the primary site can often be identified by the histopathological features. Accordingly, when malignant head and neck tumours are suspected of being metastatic in character, it is important to search carefully for the primary site.

Extramedullary plasmacytoma of the larynx.

A case of IgD myeloma in a 54-year-old male with a long-standing history of extramedullary plasmacytoma involving the larynx is reported. The patient was treated with radiation therapy and laryngectomy. Twelve years later, he complained of nasal bleeding. On examination he was found to have large masses in the left nasal cavity and in the left supraclavicular region. Histological examination of both lesions showed plasmacytoma. Serum immunoglobulin studies revealed an IgD monoclonal spike of the lambda type. Bence-Jones protein was present. Using the immunoperoxidase staining technique, cytoplasmic monoclonal IgD was detected.

Inhibition by omega-conotoxin GVIA of the chronotropic responses to sympathetic and parasympathetic nerve stimulation in the isolated, blood-perfused atrium of the dog.

1. We investigated the effects of omega-conotoxin GVIA (omega-CgTX), a blocker of N-type voltage-operated calcium channels, on the chronotropic response to stimulation of the intracardiac sympathetic and parasympathetic nerves in the isolated, blood-perfused right atrium of the dog. 2. omega-CgTX (0.3-3 nmol) itself did not affect the sinus rate significantly, but it inhibited the negative followed by positive chronotropic response to simultaneous stimulation of sympathetic and parasympathetic nerves in a dose-dependent manner. 3. omega-CgTX at higher doses (1-3 nmol) inhibited the positive response to sympathetic stimulation more strongly than the negative response to parasympathetic stimulation. omega-CgTX (3 nmol) abolished the positive chronotropic response to sympathetic nerve stimulation in the atrium treated with atropine, but did not abolish the negative response to selective parasympathetic stimulation. Neither the chronotropic response to noradrenaline nor the response to acetylcholine was affected by omega-CgTX. 4. These results indicate that omega-CgTX inhibits not only the response to sympathetic stimulation but also the response to parasympathetic stimulation in the dog heart and it inhibits the positive chronotropic response to sympathetic stimulation more strongly than the negative chronotropic response to parasympathetic stimulation.

[A case of isolated coronary ostial stenosis in a middle-aged woman].

Coronary ostial stenosis with otherwise normal coronary vessels occurs in patients with syphilis or Takayasu's aortitis. Iatrogenic ostial stenosis may develop as a complication of coronary angiography or after coronary perfusion at the time of cardiac surgery. Isolated ostial stenosis in the absence of these factors has been reported infrequently and its unique clinical and angiographic profile has been noted recently. Hence, it is proposed that this type of isolated ostial stenosis may represent a clinical entity distinct from the usual atherosclerotic coronary disease. We report the case of a middle-aged woman with this type of isolated coronary ostial stenosis. A 55-year-old female was admitted with the complaint of exertional chest pain, which had appeared 2 months admission and which had gradually become more frequent. The ECG on admission was normal. She had no coronary risk factor. Treadmill exercise test was stopped at stage 2 of Bruce protocol because ischemic S-T segment depression appeared in II, III, aVF, V4-V6 and she complained of a chest pain. Coronary angiography showed a 90% stenosis of the left coronary ostium with normal distal vessels. The right coronary artery was normal. A coronary artery bypass graft to the left anterior descending branch was performed uneventfully and the patient remains asymptomatic.

A bradycardic agent, UL-FS 49, increases atrial force and decreases ventricular force in isolated, perfused heart preparations of dogs.

We investigated the effects of a bradycardic agent, UL-FS 49 (1,3,4,5-tetrahydro-7,8-dimethoxy-3[3-[[2-(3,4-dimethoxyphenyl) ethyl]methylimino]propyl]-2H-3-benzazepin-2-on hydrochloride), on the sinus rate and atrial contractile force and the ventricular force in the isolated, blood-perfused right atrial and left ventricular preparations of the dog and the inhibition by UL-FS 49 of the negative cardiac responses to acetylcholine, adenosine and cromakalim. UL-FS 49 (0.003-3 mumol) decreased sinus rate, increased atrial force and decreased ventricular force in a dose-dependent manner. The threshold doses of UL-FS 49 (0.03 mumol) for atrial responses were smaller than that (1 mumol) for a ventricular response. The duration of bradycardia induced by UL-FS 49 was longer than the intropic one. Propranolol and atropine did not block the positive inotropic and negative chronotropic responses to UL-FS 49, respectively, in isolated atria. UL-FS 49 (0.1-3 mumol) dose-dependently inhibited the negative chronotropic and inotropic responses to parasympathetic nerve stimulation and acetylcholine exogenously administered. UL-FS 49 at higher doses (1 and 3 mumol) attenuated the negative inotropic but not chronotropic responses to adenosine and cromakalim.(ABSTRACT TRUNCATED AT 250 WORDS)

[Angiogenesis in head and neck tumor].

To clarify the correlation between tumor angiogenesis and tumor growth in head and neck carcinomas, we investigated the number of microvessels, using immunohistochemical factor VIII. No correlations among this number, differences in the primary lesion, histological differentiation and T classification were detected. The incidence of neck lymph node metastases increased as microvessel numbers increased in tumor sites. The number of microvessels increased as N and Stage classification progressed. The number of microvessels in CR cases after induction chemotherapy were increased. The numbers of microvessels in patients without recurrence were apparently greater than those in patients with recurrence. The results of this study suggest that the number of microvessels in a primary tumor correlates with the metastatic ability of the tumor.

[A case of angina pectoris and aortic regurgitation combined with thymoma].

A case of a 72-year-old female with obstruction of LAD, stenosis of RCA, aortic regurgitation in moderate degree and an anterior mediastinal mass of 7 cm in diameter, is reported. Coronary artery bypass grafting, aortic valve replacement and thymectomy were simultaneously performed. On microscopic examination, the tumor was diagnosed as a mixed typed thymoma in the first stage of Masaoka's classification. She was making satisfactory progress without recurrence, after the operation. There was no case has been reported previously in the world in which simultaneous operations were performed for angina pectoris, aortic regurgitation and thymoma.

Positive chronotropic and inotropic responses to BRL 37344, a beta 3-adrenoceptor agonist in isolated, blood-perfused dog atria.

We investigated the chronotropic and inotropic responses to BRL 37344 (a beta 3-adrenoceptor agonist) and isoproterenol in isolated, blood-perfused dog atria. BRL 37344 (0.1-30 nmol) or isoproterenol (0.001-0.3 nmol) increased the sinus rate and contractile force dose dependently. BRL 37344 was 290 times less potent than isoproterenol to increase sinus rate and 140 times less potent to increase atrial force. Both propranolol and bisoprolol similarly inhibited the positive chronotropic and inotropic responses to BRL 37344 and isoproterenol dose dependently. ICI 118,551 (0.1 and 1 nmol) did not significantly affect the positive cardiac responses to BRL 37344 or isoproterenol. Neither imipramine nor tetrodotoxin significantly affected the positive cardiac responses to BRL 37344. These results suggest that the positive chronotropic and inotropic responses to BRL 37344 are mediated mainly by beta 1-adrenoceptors in the dog heart. It is unlikely that beta 3-adrenoceptors, as previously reported in adipose tissue or gastrointestinal smooth muscle, mediate chronotropic and inotropic responses in the normal dog heart.