Hashimoto's encephalopathy presenting with micrographia as a typical feature of parkinsonism.

We describe here a 63-year-old woman who presented with gait disturbance and micrographia. Laboratory tests demonstrated the presence of anti-thyroperoxidase (TPO) antibodies and vitamin B(12) deficiency accompanied by the presence of anti-parietal cell antibodies. Lymphocytosis with increased protein was detected in cerebral spinal fluid (CSF). Serum autoantibodies against the anti-NH(2) terminal of α-enolase (NAE), a specific diagnostic marker for Hashimoto's encephalopathy (HE), were also detected. Since underlying autoimmune conditions were suspected to be associated with Hashimoto's disease, steroid therapy was conducted, and the neurological symptoms improved a few days after the therapy was started. Attention should be given to the possibility that typical parkinsonism showing micrographia is caused by HE.

Resistance of primary cultured mouse hepatic tumor cells to cellular senescence despite expression of p16(Ink4a), p19(Arf), p53, and p21(Waf1/Cip1).

Primary cultured mouse hepatic cells become senescent within a short period, although rare cells form colonies from which continuously proliferating cell lines can be established. In contrast, hepatic tumor (HT) cells show little senescence and higher colony-forming capacity. To assess this difference, we investigated p16(Ink4a)/p19(Arf)/p53/p21(Waf1/Cip1) expression in primary normal and HT cells, together with cell lines established from both. In primary normal cells, p16(Ink4a)/p19(Arf) were expressed only in association with senescence and disappeared at later stages of colony formation. In contrast, primary HT cells showed sustained p16(Ink4a)/p19(Arf) expression from the beginning. No p16(Ink4a)/p19(Arf) alterations, such as deletion, mutations, or hypermethylation, were detected in the primary HT cells, although most cell lines derived from either normal or HT cell colonies lost p16(Ink4a) or p19(Arf) expression owing to hypermethylation or homozygous deletion of p16(Ink4a)/p19(Arf). On the other hand, primary normal and HT cells and most cell lines showed constitutively elevated expression of p53/p21(Waf1/Cip1), with a further increment after ultraviolet ir-radiation, indicating a functionally normal p53 pathway. These results indicate that primary HT cells are resistant to senescence despite retaining p16(Ink4a)/p19(Arf)/p53/p21(Waf1/Cip1) expression and that loss of p16(Ink4a)/p19(Arf) function is associated only with establishment of the cell lines.

Glycoprotein IIb/IIIa antagonist FK633 could not prevent neointimal thickening in stent implantation model of canine coronary artery.

The platelet glycoprotein (GP) IIb/IIIa receptor antagonist appears to reduce the need for revascularization after coronary angioplasty. However, since the effect of GP IIb/IIIa receptor antagonist on the in-stent neointimal thickening has not been clarified, we examined it in the canine model. The beagle dogs were assigned to the control (n=7) or the GP IIb/IIIa receptor antagonist FK633 group (n=7). FK633 was administered by subcutaneous osmotic pumps (0.2 mg. kg-1. h-1) and an intravenous bolus injection (1 mg/kg) before stenting. A coil stent was implanted in the left circumflex coronary arteries. The platelet aggregation capability was significantly (<5%) and consistently reduced by FK633 except for the mild elevation (10% to 30%) on the next day of stenting. Hearts were excised 3 months after stent implantation. The area of intima and media and the area stenosis were obtained from the sections of the stented arteries. The area of intima and media and the area stenosis (1.3+/-0.2 mm2, 41.8+/-7.5% and 1.3+/-0.2 mm2, 33.9+/-6.7% in the FK633 and the control group, respectively) were not different between the groups. We conclude that, although GP IIb/IIIa antagonist FK633 prevented the platelet aggregation significantly and consistently, it could not prevent the neointimal thickening after stent implantation in canine coronary artery.

A new preshaped catheter for right ventriculography with minimal artificial tricuspid regurgitation.

A new type of preshaped angiographic catheter for right ventriculography to be inserted from the femoral vein has been developed. Right ventriculography using this catheter was conducted in about five hundred clinical cases. The result has revealed that this catheter is very useful in clinical settings without causing catheter-induced tricuspid regurgitation (TR) allowing easier and safer right ventriculography as compared with conventional catheters.

Endoscopic follow-up study of development of gastric antral vascular ectasia associated with liver cirrhosis.

Gastric antral vascular ectasia is an important cause of chronic gastrointestinal blood loss. However, its development and progression have not yet been clarified. We investigated its early lesions and progression by reviewing endoscopic films of five patients with gastric antral vascular ectasia followed for liver cirrhosis. In all patients, early findings were prepyloric red spots. In two patients, anemia due to gastrointestinal bleeding was already observed when vascular lesions were confined to the distal antrum. In the other three patients, anemia was observed 1-2 years after they showed a diagnostic pattern of gastric antral vascular ectasia. The vascular lesions gradually thickened and extended throughout the antrum, with the complete picture shown in 1.5-5 years. The pattern of distribution was classified into three types: diffuse spotty, diffuse confluent, and striped. These types could be predicted before the complete formation. Gastric antral vascular ectasia associated with liver cirrhosis started as prepyloric red spots and extended to the proximal antrum in various ways and varying time courses of less than 5 years; this entity may cause hemorrhage even in the early stage.

Phimosis of infants and young children in Japan.

The prepuce and glans was examined in 4521 healthy infants and young children with a birthweight over 2600 g. There were 3238 infants aged 1-12 months and 1283 children aged 3 years. There is no custom of circumcision in Japan. The term phimosis implies the adhesion of the prepuce and glans, which cannot be separated by manipulation. Phimosis was found in 88.5% of infants aged 1-3 months, and the corresponding figures at the ages of 4-6 months, 7-9 months, 10-12 months and 3 years were: 74.4, 63.9, 58.0 and 35.0%, respectively. However, cases where the prepuce could be retracted by gentle manipulation were found in 3.0% of infants aged 1-3 months, 19.9% of those aged 10-12 months and increased to 38.4% of children aged 3 years, which exceeded the rate of phimosis. The complete adhesion of prepuce and glans was found in many infants, and a small space between the prepuce and glans was observed in some cases of 3-year-old boys. The smegma was notable in only 16 cases (0.5%) of infants and in 5 cases (0.4%) of the 3-year-olds. Balanopothitis was found in only one case of the 3-year-olds. It is not recommended to separate the foreskin by manipulation, which sometimes leads to bleeding or paraphimosis. And it is not necessary to surgically correct phimosis in infancy and early childhood except in the case of accompanying urological disturbance.

Evaluation of combined therapy with chemoembolization and ethanol injection for advanced hepatocellular carcinoma.

To evaluate the therapeutic efficacy of transcatheter arterial chemoembolization (TACE) combined with percutaneous ethanol injection therapy (PEIT) for advanced hepatocellular carcinoma, we studied the effectiveness of TACE therapy combined with PEIT (50 cases) and TACE alone (50 cases). In both groups, patients had multiple lesions, or a single lesion with a diameter exceeding 2 cm or with vascular invasion (stages II, III, and IV in the tumor staging classification of the Liver Cancer Study Group of Japan). The clinical features in the two groups were comparable. The cumulative survival rates with TACE-PEIT were 95.0% for 1 year, 72.5% for 2 years, and 50.0% for 3 years, whereas the rates with TACE alone were 92.5% for 1 year, 57.5% for 2 years, and 20.0% for 3 years. The survival rate in the TACE-PEIT group was significantly higher than that in the TACE alone group. Moreover, the survival rate of patients with stage II or III disease in the TACE-PEIT group was significantly better than that in the TACE alone group, and the survival rate of patients with Child's classification B or C in the TACE-PEIT group was significantly higher than that in the TACE alone group. Multivariate analysis using Cox's proportional hazard regression model showed that the most significant prognostic factors in the TACE-PEIT group were tumor embolus in the portal vein and the number of tumors. These results suggest the effectiveness of combining TACE and PEIT for the treatment of advanced hepatocellular carcinoma.

[Oxidative energy metabolism and cardiac contractility in rat heart during graded reductions of coronary flow].

The relationships between cardiac contractility, myocardial oxygenation and high energy phosphates content were evaluated during graded reduction of coronary flow in the isolated rat heart. Myocardial oxygenation and high energy phosphates content were measured by optical and 31P-NMR methods, respectively. The rate-pressure product decreased along with flow rate reduction. Phosphocreatine to inorganic phosphate ratio (PCr/Pi) was unchanged until the coronary flow was reduced to 2 ml/min and started to decrease below 2 ml/min. No significant change in ATP was noted until the coronary flow was reduced to 0.5 ml/min. The oxygenation state of myoglobin and cytochrome-aa3 remained at aerobic level until the flow rate was decreased to 2 ml/min. When the coronary flow rate was reduced below 2 ml/min, cytochrome-aa3 was reduced in parallel with the deoxygenation of myoglobin. These results suggest that the mechanism of decreased contractility modulated by reduction of coronary flow is independent of oxidative energy production. We conclude that this mechanism is not caused by the reduced oxygen delivery to tissue, but that the heart senses either the reduction of coronary flow or pressure.

Effects of dihydroheptaprenol on neutrophil functions in calves.

Microemulsified dihydroheptaprenol (DHP) was administered intramuscularly to clinically healthy calves at doses of 4, 6 and 8 mg/kg body weight. Marked increase of neutrophil counts was observed 0.5, 1 and 2 days after the injection at a dose of 6 mg/kg. Nitroblue tetrazolium reducing activity of neutrophils was also obviously enhanced 1, 2 and 3 days after DHP administration. Phagocytic killing of Staphylococcus aureus by neutrophils was further enhanced markedly 1, 2 and 3 days after the drug injection at 6 mg/kg.

[Selection of candidates for a ventricular assist device as a bridge to heart transplantation].

This study was undertaken to see how many people could receive the ventricular assist device (VAD) as a bridge to heart transplantation and to get selection criteria of the recipient. From January 1984 to December 1987, 9916 patients were admitted to our institute and 399 cases of them were dead. All dead cases were examined in terms of age, heart disease, other organ function, infection, and so on. There were 42 possible candidates for VAD, 31 men and 11 women. The average age was 50 years with a range from 22 to 63 years. Ten cases (23.8%) of them had the indication for VAD bridge to transplantation. The criteria for transplantable patients included the following three categories: I) Cardiogenic shock: Irreversible left or double ventricular failure with or without life-threatening dysrhythmia during IABP therapy--4 cases. II) End-stage valvular heart disease; Operation under VAD stand-by--2 cases. III) Postoperative refractory ventricular pump failure: Failure to wean from assist circulation after IABP trial or sustained ventricular failure under IABP support--4 cases. It was indicated that continuous precise evaluation of the deteriorating hemodynamics and the intensive care for major organ functions (renal, pulmonary, neurologic, hepatic, coagulation, etc.) were important to select the candidate for VAD bridge to heart transplantation.

[Successful repair of tetralogy of Fallot with severe right ventricular dysfunction using veno-arterial bypass in an adult].

A 35-year-old male with tetralogy of Fallot, who had undergone left Blalock-Taussig shunt at ten year old, developed severe dysfunction of right ventricle with decreased right ventricular ejection fraction of 25% and frequent premature ventricular contractions of right ventricular origin. Following intracardiac procedure, the venoarterial assist circulation was successfully employed for 9 hours, until his hemodynamic conditions were improved. This experience reemphasized the importance of right ventricular protection and mechanical circulatory assist in the surgical treatment of Fallot's tetralogy in older children and adults who developed severe right ventricular dysfunction as a natural history of this disease.

Epoxy compounds as a new cross-linking agent for porcine aortic leaflets: subcutaneous implant studies in rats.

The epoxy group of the epoxy compounds has an oxygen arm that can work as a flexible joint in a cross-linking bridge and can block not only the amino group but also the carboxy group of collagen peptide. The purpose of this study is to evaluate the anticalcification efficacy of the epoxy compounds as a cross-linking agent for xenograft bioprostheses. Porcine aortic leaflets were treated with 2% epoxy compounds and implanted in subcutaneous layer of 4-week-old rats. Measurement of calcium content showed that epoxy-treated implants received a minimal calcification: mean 0.64 micrograms/mg dry weight leaflet tissue (range 0.5-0.8; N = 7) at 1 month; mean 0.94 microgram/mg (range 0.3-1.3; N = 9) at 2 months; and mean 1.2 micrograms/mg (range 0.5-2.1; N = 10) at 3 months. Natural leaflets contained calcium of mean 0.43 microgram/mg. By contrast, glutaraldehyde-preserved implants were severely calcified: mean 91 micrograms/mg (range 41-130; N = 11) at 1 month; mean 136 micrograms/mg (range 73-205; N = 16) at 2 months; and mean 170 micrograms/mg (range 90-214; N = 21) at 3 months. The epoxy compounds provide more pronounced anticalcification effects than the glutaraldehyde under pressure load-free subcutaneous circumstances.

[Clinical study on the effects of assist bypass on left ventricular contractility].

This study was undertaken to evaluate the effects of circulatory support on cardiac function in 7 patients. They were 2 men and 5 women with of age 34-54 years; Six patients underwent mitral valve replacement and one had mitral valve plasty. End-systolic pressure/volume (ESP/ESV) representing left ventricular contractility was measured just before ECC starting and after cardiac beating began in the process of rewarming. Measurements were repeated at every, interval of 10 minutes up to 60 minutes. ESP/ESV (mmHg/ml) [% of that before ECC] were as following; before ECC: 1.69 +/- 0.68 (mean +/- SD) [100], after 10 minutes; 0.40 +/- 0.24 [25.1 +/- 13.8], after 20 minutes; 0.52 +/- 0.26 [31.5 +/- 12.9], after 30 minutes; 0.77 +/- 0.28 [47.6 +/- 10.5], after 40 minutes; 0.97 +/- 0.26 [60.5 +/- 11.3], after 50 minutes; 1.18 +/- 0.46 [70.6]8.0], after 60 minutes; 1.36 +/- 0.56[80.4 +/- 12.7]. It took 39.6 minutes to recover up to 69% of that before ECC. These data suggested that the myocardial ischemia associated with aortic cross clamping continued for at least 60 minutes after cardiac beating resumed. We concluded that assist bypass should be applied to those who could not be weaned from ECC despite adequate use of catecholamine and volume loading.

Pulmonary flow-resistance relationships in allografts after single lung transplantation in dogs.

To evaluate the applicability of single lung transplantation as a treatment of pulmonary hypertension, we investigated the relationships between the pulmonary blood flow and resistance in allografts 10 days after single lung transplantation in dogs. In eight surviving recipients and five healthy dogs (control group), pulmonary flow-resistance relationships were investigated at flows in the range of 0.3 to 2.0 L/min at 0.1 L/min increments. Resistance decreased from 2585 to 746 dyne.sec.cm-5 in the successful group (five allografts receiving complete studies) and 2400 to 891 in the control group with an increase of flow. Lung water content of the successful group was 2.0 times that of the control group (successful group, 95.6 +/- 16.7 gm; control group, 47.8 +/- 7.5 gm), and water content of the other allografts (unsuccessful group), including allografts of dogs that died before investigations, was 2.2 times that of the successful group (unsuccessful group, 211.0 +/- 89.6 gm). The chest roentgenograms of the successful group showed mild or moderate consolidations, whereas those of the unsuccessful group showed severe consolidations, but no difference was found in pulmonary flow-resistance relationships between the successful and the control groups. These results show that the allografts, which have about twice the water content of normal lung, maintain adequate pulmonary vascular function. We concluded that single lung transplantation could be an effective treatment for pulmonary hypertension.

Enhancement of phagocytosis and bactericidal activity of neutrophils in miniature pigs by dihydroheptaprenol, a synthetic polyprenol derivative.

Dihydroheptaprenol (DHP), a synthetic polyprenol derivative, markedly stimulated the generation of peripheral blood neutrophils after intramuscular injection in miniature pigs. The generated neutrophils exhibited enhanced phagocytic activity against latex particles and also enhanced killing activity against Escherichia coli. The effective dose in miniature pigs (1.4 mg/kg) was markedly less than that required in mice (100 mg/kg). These results indicate that DHP induces resistance to some bacterial infections in pigs, suggesting the applicability of DHP for humans.

[Mitral insufficiency due to ruptured chordae tendineae--clinical features, early and late results of valve replacement and repair].

To evaluate the early and late results of mitral valve replacement and reconstruction for mitral insufficiency due to ruptured chordae tendineae respectively, 74 consecutive cases were analyzed. Fifty-five (74.3%) of the patients were men, and the mean age was 48 +/- 12 years old (range 16 to 76). The causes of the mitral disease were idiopathic in 50 (67.6%), rheumatic in 7 (9.4%) and infective endocarditis in 11 (14.9%) patients. In idiopathic 50 cases, 24 had mitral valve prolapse and 16 had both mitral valve prolapse and hypertension. Forty-one (55.4%) of the patients were in NYHA functional class III or IV preoperatively. Thirty (40.5%) cases underwent surgery within one year after their initial symptoms of heart failure onsets including six emergency operation cases due to uncontrollable acute lung edema. Chordae to anterior mitral leaflet were ruptured in 31 (a5, m16, p10)[41%] patients, to the posterior mitral leaflet in 45 (a4, m23, p18)[59%], and to both leaflets in one patient. Mitral valve replacement was performed in 68 patients (91.9%) and 6 patients (8.1%) underwent mitral valve repairs. Twenty cases underwent associated procedures that included tricuspid valve annuloplasty in 8, aortic valve replacement in 5 and myocardial revascularization in 4 cases. There were two operative deaths (2.4%); both occurred after replacement, left ventricular rupture in one and DIC in one. Mean follow-up period was 4.5 years (range 1 to 17) in 67 cases. There were four late deaths; all occurred after replacement. However five patients sustained mild mitral insufficiency after mitral valve repair including one that became worse of regurgitation three years after isolated Kay's annuloplasty, there were no cases that had needed reoperation and no late death after reconstruction. Left ventricular function and pulmonary arterial pressure were almost normalized in more than 90% cases postoperatively. Our data indicated that mitral valve reconstruction (McGoon's plus Kay's method as standardized maneuver) was the procedure of choice for selected patients with mitral insufficiency owing to ruptured chordae tendineae to the posterior mitral leaflet, including more limited patients with ruptured chordae to the anterior mitral leaflet.

[Long-term results of porcine bioprosthetic heterograft; a 13-years' experience].

One hundred and ninety-four patients underwent valve replacements with the glutaraldehyde-preserved porcine bioprostheses (133 Hancock valves, 39 Angell-Shiley valves, 22 Carpentier-Edwards valves and 3 other valves) from 1974 through 1979. There were 105 women and 89 men, whose age ranged 18 to 62 (mean 38.8) years. One hundred and eighty-two patients had mitral bioprosthetic valve replacement (BVR)s, of which 52 had combined aortic mechanical valve replacements, 8 had aortic BVR's, 3 had tricuspid BVR's and 3 had multi-BVR's. Operative mortality was 10.8%. Only one patient was lost to follow-up. Cumulative duration of follow-up is 1421 patient-years. Linearized rate of anticoagulant related hemorrhage, thromboembolism (TE), prosthetic valve endocarditis (PVE), primary tissue failure (PTF) and valve dysfunction (VD) were 0.07, 1.62, 0.49, 2.74 and 3.66% per patient-year. Actuarial freedom from TE, PVE, PTF and VD were 87.0 +/- 2.7%, 95.6 +/- 1.5%, 65.2 +/- 4.9% and 56.9 +/- 5.6% at 13 years. Actuarial survival rate was 67.4 +/- 4.0% at 13 years. Long term follow-up after valve replacement with porcine bioprosthetic valve confirms low thrombogenicity. But primary tissue failure was the chief cause of valve dysfunction and represent a major problem. At this time, we are going to use porcine bioprosthetic valve in the selected patients, that is in the situations in which anticoagulation is contraindicated.

[Limitations and extension of surgical indications for acquired valvular heart disease; retrospective study of hospital death].

Between 1981 and 1987, valvular surgery was performed in 988 patients, 27 of which were dead before discharge. Among them, 14 patients of cardiac deaths due to low cardiac output syndrome (LOS) and arrhythmias were analyzed to withdraw factors correlated with their cause of death. There was a tendency for the patients with stenotic valvular disease to die of LOS and regurgitant valvular lesions of arrhythmias. Statistical analysis showed the cause of deaths were multifarious including pulmonary, hepatic and renal failure, so no definite factor was pointed out. Case study of typical limited and extended surgical indications revealed (1) the patients with mitral stenosis combined with organic tricuspid regurgitation and RV/LV EDVI ratio over 1.5, and (2) the patients with aortic insufficiency and LVEDVI over 400 ml/m2 or LVESVI over 300 ml/m2 were candidate for hospital death after valve replacement. Extended approach for those patients should be two staged heart transplantation using ventricular assist device.