[A case of central retinal vein occlusion forming the epiretinal membrane].

BACKGROUND: We encountered a patient with central retinal vein occlusion (CRVO) forming an epiretinal membrane (ERM) in a wide area. Generally formation of ERM is rare in CRVO. PATIENT AND METHODS: The patient was a 72-years-old female with ischemic CRVO in the right eye, who had undergone insufficient pan-retinal photocoagulation. Since ERM was formed in a wide area 7 months after the occurrence of CRVO, the patient underwent vitrectomy. RESULTS: Although the patient was elderly, the posterior vitreum had not been detached, and ERM was observed in a wide area from the disk of the optic nerve over the vascular arcade. Since the ERM strongly adhered to the retina, incision of the membrane with vitreous scissors was required. The membrane tissue collected during the operation showed few vascular and cellular components, and consisted of ERM extracellular matrices such as collagen. CONCLUSIONS: In this patient, however, it was probable that not only barrier dysfunction of retinal vessel endothelial cells caused by elevated pressure in the retinal vein and rapid retinal ischemia but also the anatomical feature of the undetached posterior vitreum was involved in the formation of the ERM.

Atrioventricular (AV) nodal reentry associated with 2:1 infra-His conduction block during tachycardia in a patient with AV nodal triple pathways.

We report a patient with atrioventricular (AV) nodal reentry in which a 2:1 infra-His conduction block was demonstrated during tachycardia. The electrocardiogram (ECG) at the time of attack showed two types of supraventricular tachycardias. The first type was a narrow QRS tachycardia associated with 1:1 AV conduction at a rate of 170 beats/minute. The second type was a narrow QRS associated with 2:1 AV block at a rate of 85 beats/minute. Electrophysiological study revealed AV nodal reentry based on AV nodal triple pathways. The AV conduction curve obtained by atrial premature stimulation showed two discontinuous points at two different basic cycle lengths (500 msec, 400 msec) and from two different pacing sites (high right atrium, distal coronary sinus). These two types of tachycardias were induced by both atrial premature and overdrive stimulation. In the first type, the impulse conducted in the slow pathway antegradely with 1:1 AV conduction and in the fast pathway retrogradely. In the second type, the impulse was conducted beat-to-beat by either a slow pathway or a very slow pathway antegradely with the retrograde limb being the fast pathway and 2:1 infra-His conduction block. Only when the impulse was conducted in the slow pathway antegradely was the infra-His conduction block observed during the tachycardia. The tachycardia in this patient was drug refractory and controlled by an anti-tachycardia pacemaker.

Atrioventricular (AV) reciprocating tachycardia utilizing left lateral AV bypass pathway with a long retrograde conduction time.

A 52-year-old man had suffered from attacks of palpitation for 10 years. The frequency of the attacks had been increasing since June 1991. The electrocardiogram (ECG) at the time of attack showed a heart rate of 175 bpm and RP'/P'R > 1, indicating long RP' tachycardia. Electrophysiological examination of the heart revealed an accessory pathway in the left lateral position. During the tachycardia, PVCs from the right ventricular apex (RVA) captured the atria. On the basis of these findings the patient was diagnosed as having had atrioventricular (AV) reciprocating tachycardia (AVRT). Ventriculoatrial (VA) conduction indicated a decremental conduction curve by single premature stimulation from the RVA, and the atrial cycle length following PVC during tachycardia was prolonged (paradoxical delay). When verapamil was administered intravenously, tachycardia induced by the premature stimulation showed prolongation of the VA interval, associated with an increased tachycardia cycle length. Tachycardia in this patient was completely controlled by administration of verapamil.

Electrophysiologic changes before onset of ventricular tachyarrhythmias during partial reperfusion following severe myocardial ischemia in dogs.

We examined the electrophysiologic changes before an onset of ventricular tachyarrhythmia during partial reperfusion following severe myocardial ischemia. The left anterior descending coronary artery was occluded and cannulated below the occluded portion in 26 dogs. To deplete collateral flow into the ischemic myocardium, retrograde blood flow was induced for 20 min. Then, in all dogs except 7 with ventricular fibrillation during retrograde blood flow, partial reperfusion through collateral flow into the ischemic myocardium was produced by stopping the retrograde flow. Within 2 min of partial reperfusion, sustained ventricular tachycardia (VT) occurred in 7 dogs (group A) and non-sustained VT degenerating ventricular fibrillation occurred in 11 dogs (group B) of the remaining 12 dogs. In 6 dogs of group A and 9 of group B, epicardial conduction block appeared 5.0 +/- 2.2 and 3.5 +/- 1.3 min after ischemia. This was followed by fractionated electrical activities 15.2 +/- 3.2 and 11.7 +/- 3.3 min after ischemia. In group A, the fractionation had a slight change in configuration and a small increase in amplitude before the onset of VT during reperfusion; in group B, new deflections with large amplitude emerged before it. There was a significant difference in the amplitude (0.38 +/- 0.2 vs 0.67 +/- 0.3 mV, p < 0.025) between the 2 groups, although there was no significant difference in the amplitude (0.33 +/- 0.2 vs 0.23 +/- 0.1 mV) of the fractionation just before reperfusion. Our results show that slight improvement in fractionation induces sustained VT, and new deflections induce non-sustained VT degenerating ventricular fibrillation, even during partial reperfusion.

[Mitoxantrone and conventional-dose cytosine arabinoside for relapsed and refractory acute leukemia].

Fourteen patients with relapsed or refractory acute leukemia received combination chemotherapy of mitoxantrone 6 mg/m2/day intravenously for three to six days and cytosine arabinoside 60 mg/m2/day intravenously over 24 hours continuously for five to ten days. Complete remission was attained in six patients (42.9%) and partial response in two patients (14.3%). Six patients (42.9%) had resistant disease, and four patients (28.6%) died during the myelosuppressive phase. Of the patients achieving complete remission, four relapsed and other two continued complete remission up to 27.3 months. Median remission duration was approximately 10.6 months. No significant difference was found with regard to the efficacy of our regimen between AML and ALL. Hematological toxicity was no more severe than the prior cumulative chemotherapy. Major non-hematologic side effects were nausea and vomiting (71.4%), stomatitis (64.3%) and liver dysfunction (57.1%), which were moderate and manageable, while no cardiotoxicity was observed in any patient. In conclusion, the combination chemotherapy of mitoxantrone and conventional dose cytosine arabinoside is an effective salvage therapy in relapsed or refractory acute leukemia, and our regimen has possible utility as first-line chemotherapy in de novo acute leukemia also.

Double atrial response to a single ventricular extrastimulus in a patient with Wolff-Parkinson-White syndrome.

Electrophysiological examination in a 39-year-old male disclosed an accessory pathway between the right atrium and the right ventricle and AV nodal dual pathways. Atrial and ventricular extrastimuli induced paroxysmal supraventricular tachycardia (PSVT), which was shown to be AV reciprocating tachycardia. Double atrial response was noted during ventricular extrastimuli at V1V2 of 280 msec and V1V2 of 250 msec. The first atrial response is considered to have been transmitted in a retrograde fashion in the accessory pathway, and the second atrial response similarly in the slow pathway of the AV node.

Myocardial blood flow, alternans of ST segment elevation, conduction delay and ventricular arrhythmia during acute myocardial ischemia with and without retrograde blood flow in canine hearts.

The technique of retrograde blood flow has been shown to decrease collateral flow into the ischemic myocardium, and to cause severe myocardial ischemia in dogs. Ischemia with retrograde blood flow in dogs is similar to ischemia in human hearts. Therefore, we examined the effect of retrograde blood flow on myocardial blood flow, ST segment elevation, alternans of ST segment elevation, conduction delay and ventricular arrhythmia in dogs. Sixty dogs were divided into two groups. In group A (N = 32), the left anterior descending coronary artery was occluded for 10 min. In group B (n = 28), ischemia was induced by the technique of retrograde blood flow for 10 min. During ischemia, the myocardial blood flow at the ischemic zone measured by a H2 gas clearance method was 11.2 +/- 1.6 in group A and 5.7 +/- 0.7 ml/min/100 g in group B (p less than 0.01). The maximal ST segment elevation was 13.6 +/- 1.9 in group A and 27.2 +/- 2.1 mV in group B (p less than 0.001); the maximal alternans of ST segment elevation was 5.3 +/- 1.1 in group A and 10.1 +/- 1.4 mV in group B (p less than 0.01); the maximal conduction delay was 51.6 +/- 8.4 in group A and 111.1 +/- 6.2 msec in group B (p less than 0.001); and the incidences of ventricular premature beats (greater than 5/min), ventricular tachycardia and fibrillation were 34%, 41% and 22% in group A, and 68%, 79% and 25% in group B (p less than 0.01, p less than 0.01 and not significant, respectively). It is concluded that ischemia with retrograde blood flow can be used to examine occlusive and reperfusion ventricular arrhythmia in dogs, because the incidences of ventricular premature beats and ventricular tachycardia were high, but that of ventricular fibrillation was not high despite the severe ischemia.

Purification and characterization of novel heparan sulfate proteoglycans produced by murine erythroleukemia cells in the growing phase.

Murine erythroleukemia cells (Friend erythroleukemia cells of a C-10-6 line) synthesized sulfated glycosaminoglycans consisting mainly of heparan sulfate (more than 95%) with a small amount of chondroitin 4-sulfate. The heparan sulfate occurred as proteoglycans, of which the cell-associated component was separated into urea-insoluble (UI) and urea-soluble (US) fractions. The UI proteoglycan consisted of a single homogeneous molecular species with an estimated Mr of 360,000 (C(UI)PG), whereas the US component was composed of two subfractions: a homogeneous species with an Mr of 280,000 (C(US)PGI) and a mixture of compounds with Mr values of less than 80,000 (C(US)PGII), which were isolated in yields of about 110, 340, and 80 micrograms of hexuronate (HexUA), respectively, from 1.37 g of an acetone powder prepared from 5.7 x 10(9) cells in the logarithmic phase of growth. The proteoglycan released into the medium (12 liters) was a single homogeneous species with an Mr of 320,000 (MPG) which was purified in a yield of 500 micrograms of hexuronate. The major, cell-associated proteoglycan, C(US)PGI, had very high contents of serine and glycine, accounting for approximately 80% of the total amino acids. This proteoglycan as well as the other two large proteoglycans, C(UI)PG and MPG, were highly resistant to degradation by various proteinases. These three proteoglycans, C(UI)PG, C(US)PGI, and MPG, had heparan sulfates with estimated Mr values of 32,000, 27,000, and 30,000. On the other hand, the Mr of the smaller proteoglycan, C(UI)PGII, was not significantly different before and after beta-elimination, indicating that it contains only a small peptide, if any. The heparan sulfate of this proteoglycan consisted of smaller and heterogeneous molecular species with Mr values of 26,000, 20,000, and 4,000. Digestion of these heparan sulfates with heparitinase I plus II resulted in almost complete depolymerization and gave six unsaturated disaccharides, delta HexUA-GlcNAc, delta HexUA-Glc-NAc(6-SO4), delta HexUA-GlcNSO3, delta HexUA-GlcNSO3 (6-SO4), delta HexUA(2-SO4)-GlcNSO3, and delta HexUA(2-SO4)-GlcNSO3(6-SO4). The relative amounts of these disaccharides generated from the individual heparan sulfates showed that an average ratio of sulfate residues to repeating disaccharide units of the C(US)PGII-derived heparan sulfate (0.97) was significantly higher than those of the other three large proteoglycan-derived glycosaminoglycans (0.54-0.70).

Effect of pre-existing four hour coronary stenosis on ventricular arrhythmias during a subsequent 10 minute occlusion in dogs.

STUDY OBJECTIVES: The aim was to assess the effect of pre-existing coronary stenosis on ventricular arrhythmia during subsequent acute coronary occlusion. DESIGN: Dogs with a 4 h intact interval followed by a 10 min occlusion of left anterior descending coronary artery (group A) were compared for ventricular arrhythmias with dogs with a 4 h stenosis of the same artery followed by a 10 min occlusion (group B). Myocardial blood flow was measured in the ischaemic myocardium using the H2 gas clearance method to exclude dogs with good collateral flow (myocardial blood flow greater than 11.0 ml.min-1.100g-1). EXPERIMENTAL ANIMALS: 35 mongrel dogs of either sex, weight range 11-26 kg, were used in the experiments (group A, n = 17; group B, n = 18). After exclusion of dogs with good collateral circulation there were 11 dogs in group A (subgroup A1) and 12 dogs in group B (subgroup B1). MEASUREMENTS AND MAIN RESULTS: The incidence of ventricular fibrillation was lower in group B (pre-existing stenosis) than in group A during the 10 min occlusion, though there was no difference in numbers of ventricular premature beats. Maximum ST segment elevation and maximum conduction delay were less in group B than in group A, but myocardial blood flow did not differ during the 10 min occlusion. In the subgroups the incidence of both types of ventricular arrhythmia was lower in subgroup B1 during the 10 min occlusion, while the maximum ST segment elevation and maximum conduction delay were less, and myocardial blood flow was greater. CONCLUSIONS: Pre-existing 4 h coronary stenosis causes the development of collateral flow and reduces the incidence of ventricular arrhythmias during subsequent occlusion.

Ventricular fibrillation during partial reperfusion following severe myocardial ischemia in the canine model.

The authors examined whether partial reperfusion protects against reperfusion ventricular fibrillation (VF) following severe acute myocardial ischemia. Fifty-seven dogs were divided into two groups. In group A (n = 21), the left anterior descending coronary artery was occluded for 10 minutes, followed by full reperfusion. In the remaining 36 dogs (group B), myocardial ischemia was induced by retrograde blood flow (RBF) for 10 minutes. Thereafter, these dogs were divided into three subgroups: in group B1 (n = 10), full reperfusion was made by a carotid-left anterior descending coronary artery bypass; in group B2 (n = 13), partial reperfusion was achieved by collateral flow into the ischemic zone due to stopping RBF; in group B3 (n = 13), RBF was continued for an additional 5 minutes. During 10 minute ischemia, the myocardial blood flow at the ischemic zone measured by the H2 gas-clearance method was 12.3 +/- 2.0 ml/min/100 g in A, 3.4 +/- 0.9 ml/min/100 g in B1, 4.7 +/- 0.6 ml/min/100 g in B2, and 4.7 +/- 0.6 ml/min/100 g in B3 (A vs B1, p less than 0.02; A vs B2 and B3, p less than 0.01). Maximal ST-segment elevation was 11.4 +/- 1.8 mV in A, 28.2 +/- 2.7 mV in B1, 25.1 +/- 3.0 mV in B2, and 27.0 +/- 1.9 mV in B3 (A vs B1, B2, and B3, p less than 0.001). Maximal conduction delay was 48.6 +/- 9.4 ms in A, 106.4 +/- 5.2 ms in B1, 101.6 +/- 9.9 ms in B2, and 91.2 +/- 5.1 ms in B3 (A vs B1, B2, and B3, p less than 0.001). The incidence of reperfusion VF was 14% (3/21) in A, 80% (8/10) in B1, and 69% (9/13) in B2 (A vs B1, p less than 0.001; A vs B2, p less than 0.005). In group B3, VF occurred in only 1 of 13 dogs for the additional 5 minutes. It is concluded that reperfusion VF occurred frequently when ischemia was severe even though the duration of ischemia was short (B1), and that reperfusion VF was not prevented by partial reperfusion when the ischemia was severe (B2).

[Pure red cell aplasia with inhibitor to erythroid precursors in serum].

A patient with pure red cell aplasia (PRCA), who had the inhibitor to erythroid precursors in serum, is described. A 72-year-old female was referred to Nagoya National Hospital because of progressing anemia in April 1988. On admission, her hemoglobin was 4.8 g/dl, reticulocyte 0.8%, and bone marrow specimen contained only 1.2% erythroblast. On these bases, she was diagnosed as pure red cell aplasia. After small amount of blood was transfused, her hemoglobin and erythroblast in bone marrow (EBM) increased to 7.8 g/dl and 39.1%, respectively, and she was discharged. However, after a month, her hemoglobin dropped to 4.6 g/dl, reticulocyte to 0.1%, and EBM to 0%. Soon after corticosteroid therapy (prednisolone, 40 mg, daily) was started, a marked elevation of reticulocyte count was observed, and then her hemoglobin increased to 11.0 g/dl, and EBM to 31.6%. The reason for a transient spontaneous remission at the onset of her disease was occurred is unclear. The number of BFU-E in her bone marrow was within normal range, but it was suppressed significantly (65%) after the addition of her serum and the complement purified from rabbit plasma. This finding suggest the presence of inhibitor to erythroid precursors in her serum.

[IgM myeloma without depression in serum IgG and IgA--a case report].

A 64-year-old woman with a monoclonal gammopathy was admitted to Nagoya National Hospital with the complaint of occasional hemoptysis. On examination, there was no hepatosplenomegaly or no lymphadenopathy. The hemoglobin was 10.1 g/dl; platelets 22.5 X 10(4)/microliters; white blood cells 4.9 X 10(3)/microliters, with 4% of atypical lymphocytes. Immunoglobulin analysis of the serum by immunodiffusion revealed an IgG of 1,459 mg/dl, an IgA of 219 mg/dl, and an IgM of 5,091 mg/dl. Serum viscosity was 4.9. Serum immunoelectrophoresis demonstrated atypical precipitant arcs reacting with mu and kappa antisera. Urine immunoelectrophoresis showed a positive reaction against kappa antiserum. Radiologic studies of the bones revealed generalized osteoporosis with multiple punched out lesions of the skull. Thirty percent of bone marrow nucleated cells was atypical plasma cells, the presence of which was verified by electron microscopy. Although they were positive mainly for cytoplasmic mu and kappa chains by immunoperoxidase studies, cells positive for gamma, alpha, or lambda chains were occasionally found, indicating that normal immunoglobulin synthesis was not suppressed in this case of IgM myeloma.

[So-called Ph1-negative chronic myelogenous leukemia with a mosaic pattern of trisomy 8 and normal karyotypes--report of 2 cases].

Two cases of Ph1-negative chronic myelogenous leukemia (CML) are described, they were 66-year-old female and 73-year-old male. Both patients shared all of the following features: presence of anemia, thrombocytopenia and leukocytosis with every stage of neutrophilic differentiation, hypercellular bone marrow with hyperplasia of the degranulated neutrophilic series, diminished neutrophilic alkaline phosphatase, elevated serum lysozyme and vitamin B12 level, mosaic pattern of trisomy 8 and normal karyotypes in chromosome analysis, and markedly increased number of CFU-GM. In addition, bcr rearrangement by Southern blot hybridization was not demonstrated in these patients. The diagnosis of chronic myelomonocytic leukemia was not verified, however, because of the absence of monocytosis in peripheral blood. The existence of so-called Ph1-negative CML like these two cases as a diagnostic entity must be further studied.

[UFT/CDDP treatment in advanced gastric cancer--case report].

In treating advanced gastric cancer cases, 100 mg/m2 of cisplatin (CDDP) was given to such patients by means of a 24 hr continuous iv infusion once a month. This was in addition to daily UFT chemotherapy with an oral administration of UFT at a dose of 200 mg/m2 twice a day before meals. In this paper, two patients who achieved an objective tumor response to this UFT/CDDP chemotherapy are discussed. It was felt that this treatment was not likely to induce either leukocytopenia or thrombocytopenia. With regard to this drug combination, it has been reported that a remarkable, synergistic, antitumoral activity of combined 5-fluorouracil and cisplatin was demonstrated against L-1210 leukemia in BDF1 mice.

[Therapeutic treatment of Borrmann type 4 (scirrhous) gastric cancer-chemotherapy and histopathological studies].

Up to now, there has been no investigation documenting clearly the effectiveness of chemotherapy for Borrmann type 4 gastric cancer from a histopathological viewpoint. In this paper, we present a few representative cases of Borrmann type 4 gastric cancer in which microscopic examination revealed the therapeutic effectiveness (degradation of cancer cells) of neoadjuvant chemotherapy. Further, comparative studies will be needed to clarify the relationship between the assessed effectiveness of therapy by roentgenological and histopathological examination.

Analysis of fibrinogen degradation product in severe liver disorders by immunoblotting.

Increased serum fibrinogen degradation product (FDP) in liver cirrhosis and hepatic carcinoma as measured by latex agglutination was analyzed by means of SDS-polyacrylamide gel electrophoresis followed by immunoblotting with anti-fibrinogen antibody. The antibody used in this study reacts with fibrinogen, fragment X, Y, D-D, D and E. The validity of this technique was confirmed by the analysis of the serum samples from patients with definite diagnosis of disseminated intravascular coagulation. Serum samples of 14 patients out of 18 with elevated FDP values and severe liver diseases were shown to contain no plasmic digest of fibrin or fibrinogen. By using the SDS-gel electrophoresis after disulfide bond reduction, seven serum samples from these 14 patients, who were shown to have no plasmic digest in serum, were found to contain unclottable fibrinogen retained in sera, while the remaining seven samples were revealed to have fibrin monomer in their sera. Four serum samples from the 18 patients were shown to have plasmic digest of fibrinogen, but these patients had additional diseases leading to intravascular coagulation.