A decrease in membrane tension precedes successful cell-membrane repair.

We hypothesized that the requirement for Ca(2+)-dependent exocytosis in cell-membrane repair is to provide an adequate lowering of membrane tension to permit membrane resealing. We used laser tweezers to form membrane tethers and measured the force of those tethers to estimate the membrane tension of Swiss 3T3 fibroblasts after membrane disruption and during resealing. These measurements show that, for fibroblasts wounded in normal Ca(2+) Ringer's solution, the membrane tension decreased dramatically after the wounding and resealing coincided with a decrease of approximately 60% of control tether force values. However, the tension did not decrease if cells were wounded in a low Ca(2+) Ringer's solution that inhibited both membrane resealing and exocytosis. When cells were wounded twice in normal Ca(2+) Ringer's solution, decreases in tension at the second wound were 2.3 times faster than at the first wound, correlating well with twofold faster resealing rates for repeated wounds. The facilitated resealing to a second wound requires a new vesicle pool, which is generated via a protein kinase C (PKC)-dependent and brefeldin A (BFA)-sensitive process. Tension decrease at the second wound was slowed or inhibited by PKC inhibitor or BFA. Lowering membrane tension by cytochalasin D treatment could substitute for exocytosis and could restore membrane resealing in low Ca(2+) Ringer's solution.

Detection of cardiac allograft rejection and myocyte necrosis by monoclonal antibody to cardiac myosin.

Indium 111-labeled monoclonal antibody to cardiac myosin was examined for efficacy in the detection of cardiac graft rejection and rejection-related myocyte necrosis. Heterotopic heart transplants were performed in isogenic and allogenic groups of rats (n = 56). At selected intervals posttransplant, uptake of injected antibody in the donor and native hearts was determined by gamma scintillation scanning. Indium uptake was compared to histologic results graded for the severity of rejection and the presence of myocyte necrosis. The donor heart uptake of labeled antibody was significantly greater in both moderate rejection and severe rejection than in lesser degrees of rejection (P = 0.05). The donor/native heart antibody uptake ratio (AUR) in both severe and moderate rejection were significantly different from no or mild rejection (P = 0.05). In pooled grafts without myocyte necrosis, both the absolute donor heart antibody uptake and the donor/native heart AUR were significantly greater in grafts with moderate or severe rejection than in those with no or mild rejection (P less than 0.001). Among grafts with moderate or severe rejection, those with myocyte necrosis had greater donor heart antibody uptakes and greater donor/native heart AUR than grafts without myocyte necrosis (P less than 0.001). The grade of rejection and the presence of histologic myocyte necrosis appear to be closely related but independent variables, both of which influence antibody uptake. It is concluded that monoclonal antibody to cardiac myosin may be a useful noninvasive tool that could distinguish moderate or severe rejection from lesser degrees of rejection and that could detect the presence of myocyte necrosis.

Cardiac transplantation without cardiopulmonary bypass: experimental model to study growth of the transplanted heart.

An experimental model using surface-induced (20 degrees C) deep hypothermia and total circulatory arrest instead of cardiopulmonary bypass was developed for the study of growth of the transplanted heart. Autotransplantation of the heart was performed in 42 young dogs weighing from 4.4 to 9.0 kg (mean, 6.9 kg). Time of ischemia ranged from 26.0 to 60 minutes (mean, 43.4 minutes). Return of satisfactory cardiac function occurred in all but one animal. An early high mortality rate was due primarily to pulmonary complications, but with modifications to the technique, long-term survival increased to 70%. Early deaths (5 days to 13 weeks) of five dogs during preliminary trials were due to pleural effusion (2), sepsis (1), endocarditis (1), and ascites (1). There have been 14 long-term survivors (range, 194 to 498 days; mean, 264 days). Long-term survivors appear well, are active, and show satisfactory growth. This experimental model eliminates the need for heparinization and reduces the potential for complications associated with cardiopulmonary bypass in the dog. It avoids cannulations that might impinge on anastomotic sites. This model appears to be suited for studying growth of the transplanted heart.

Cardiac dilatation after cardiopulmonary bypass: ceramic plate technique for sternal splinting.

Intraoperative sternal closure after cardiopulmonary bypass in patients with cardiac dilatation and dysfunction may cause fatal deterioration of their hemodynamics. To avoid this complication, a ceramic plate made from methyl methacrylate was used for sternal splinting. This simple splint can avoid chest wall compression to the overdilated heart, maintaining stable hemodynamics after cardiopulmonary bypass without postoperative respiratory complications or mediastinal infection.

Growth of tracheal anastomoses: advantage of absorbable interrupted sutures.

Growth of the trachea after complete transection and anastomosis was studied in four groups of 1-month-old New Zealand white rabbits. The trachea was transected at the fifth cartilaginous ring and then anastomosed with continuous 6-0 polypropylene (Prolene) (group 1), interrupted 6-0 polypropylene (group 2), continuous 6-0 polydioxanone (PDS) (group 3), or interrupted 6-0 PDS (group 4). The animals were followed up for 90 to 103 days (mean follow-up, 95 days). At the time the animals were killed, body weight had increased 125% (1.2 to 2.7 +/- 0.18 kg). Growth of the trachea was assessed at the time of death. Results from this study suggest that growth of a tracheal anastomosis is retarded in a growing animal model. The degree of resultant stenosis was significantly less when an absorbable suture material (PDS) and an interrupted suturing technique were used.

Looped device for inferior vena cava taping through a right parasternal approach.

In small adults and infants, inferior vena caval taping through the right parasternal approach for minimally invasive cardiac operations is often difficult with conventional methods. We present a new convenient method to simplify this critical step.

Aortic arch aneurysm repair using selective cerebral perfusion.

Seventy-seven patients underwent aortic arch aneurysm repair using selective cerebral perfusion from January 1987 to August 1992. Early and long-term results and preoperative and postoperative cerebral function were evaluated. Cerebral function was assessed by the mini mental state-Himeji test and the Wechsler adult intelligence scale. Thirty-six patients had true aneurysms, and 41 had dissection. Hospital mortality for true and dissecting aneurysms was 19.4% and 7.3%, respectively. The 5-year actuarial survival rates for true and dissecting aneurysms were 59.0% and 65.3%, respectively (not significant). There were no significant differences in test scores before or after operation. Repair or replacement of the aortic arch using selective cerebral perfusion is a safe procedure with acceptable hospital mortality.

Expression of CD40 in the brain of Alzheimer's disease and other neurological diseases.

We have investigated immunohistochemically the expression of CD40 in post-mortem human brain tissues. In control brain, the blood vessels were stained weakly for CD40. Vascular expression of CD40 was enhanced in the lesions of Alzheimer's disease and some other neurological diseases. In such diseases, reactive microglia were also positive for CD40. The results of this study suggest that CD40 expression by microglia is up-regulated upon a variety of brain insults and is not limited to lesions with amyloid beta-protein deposits.

Glial involvement in the degeneration process of Lewy body-bearing neurons and the degradation process of Lewy bodies in brains of dementia with Lewy bodies.

Glial involvement in the degeneration process of Lewy body (LB)-bearing neurons and the degradation process of LBs in the cerebral cortex and amygdala in brains of dementia with Lewy bodies was investigated immunohistochemically. HLA-DR-positive microglia frequently extended their processes to degenerated neurons with alpha-synuclein-positive LBs, while some GFAP-positive astroglial processes attached to weakly alpha-synuclein-positive extracellular LBs. Some intracellular LBs were immunoreactive to anti-C4d antibody, and these LB-bearing neurons were involved by activated microglia. About half of the intracellular LBs were immunoreactive to anti-chromogranin-A (CGA) antibody, and most of CGA-positive LB-bearing neurons were surrounded by microglia. Although we could find no evident participation of TNF-alpha, a candidate cytokine that is up-regulated by microglia following CGA stimulation, in the degeneration process of LB-bearing neurons, some intracellular LBs were immunoreactive to the antibody to NF-kappaB, a transcriptional factor activated by cytokines. These findings suggest that microglia participate in the degeneration process of LB-bearing neurons via varying immunogenic elements including complement proteins, CGA and probably some cytokines, and that astroglia participate in the degradation process of LBs.

Dementia with Lewy bodies showing advanced Lewy pathology but minimal Alzheimer pathology--Lewy pathology causes neuronal loss inducing progressive dementia.

The present study concerns an autopsied case of dementia with Lewy bodies (DLB) showing advanced Lewy pathology but minimal Alzheimer pathology. The patient was a 50-year-old Japanese male without inheritance. His initial symptoms at the age of 43 suggested the diagnosis ofjuvenile idiopathic Parkinson's disease (PD), but were followed by memory disturbance 1 year later. He showed parkinsonism, dementia, personality change, fluctuating cognition and visual hallucinations 3 years later. Neuroradiological examination revealed moderate brain atrophy, predominantly in the frontal and temporal lobes. Neuropathological examination demonstrated a widespread occurrence of Lewy bodies (LB) with LB-related neurites not only in the brainstem but also in the cerebrum. The present case showed Lewy pathology which corresponded to stage IV by our staging and was parallel to neuronal loss. There was marked neuronal loss with many LB-related neurites in the CA2 of the hippocampus. Neurofibrillary tangles (NFT) were almost restricted to the entorhinal cortex, while senile plaques were absent. Consequently, the present case was pathologically diagnosed as having DLB of the neocortical type, pure form. In the present study, we suggest that Lewy pathology in the cerebral cortex could be responsible for progressive dementia.

Mitral valve prolapse syndrome with coronary artery spasm: a possible cause of recurrent ventricular tachyarrhythmia.

A 54-year-old man with mitral valve prolapse syndrome diagnosed by echocardiography complained of anginal pain associated with ventricular tachyarrhythmia. One day he suddenly lost consciousness, and ECG at that time revealed ventricular fibrillation. Thereafter, he developed ST elevation, sporadic premature ventricular contractions, and R on T phenomenon leading to ventricular fibrillation during the attack of anginal pain. His coronary arteriogram was normal. This case implies that coronary artery spasm may be one of the causes of chest pain and ventricular tachyarrhythmias in patients with mitral valve prolapse syndrome.

Surgical treatment for isolated hypoplasia of the right ventricle.

Four patients with isolated hypoplasia of the right ventricle who underwent intracardiac repair are described. An atrial septal defect (ASD) was successfully closed in 3 patients with mild hypoplasia of the right ventricle. The remaining patients underwent ASD closure and right atrium-to-pulmonary artery connection with a conduit with a bovine pericardial valve because of severe hypoplasia of the right ventricle and tricuspid valve. Postoperative angiocardiogram in the last patient demonstrated two-channel pathways from the right atrium to the pulmonary artery via both the right ventricle and external conduit. At long-term follow-up studies, 3 patients had developed arrhythmias and/or sinus node dysfunction, and one had died, probably because of arrhythmia, 13 years postoperatively. The right ventricular ejection fractions were below normal levels at 11 and 12 years postoperatively in 2 patients who underwent closure of ASD. It was concluded that the mild form of hypoplasia of the right ventricle should be surgically corrected by ASD closure, while right atrium-to-pulmonary artery connection or Fontan's operation should be chosen for cases of severe hypoplasia. Arrhythmias and hypofunction of the right ventricle are long-term problems after intracardiac repair of this anomaly.

Sutureless ringed graft replacement of descending thoracic aorta with extensive calcification.

A 79-year-old hypertensive woman, with fusiform shaped atherosclerotic aneurysm in the descending thoracic aorta whose medial layer was maintained by an extensive solid calcium plate (porcelain aorta), was successfully treated using a sutureless intraluminal ringed graft. Spools of the ring were fixed by circumferential ligatures at both proximal and distal sites of anastomosis and a dilated segment of the aorta was replaced with the tube graft.

Uneventful pregnancy and delivery in a case of multiple peripheral pulmonary stenoses.

The first case of multiple peripheral pulmonary stenoses undergoing uneventful pregnancy and delivery is described. The course of pregnancy in a patient with peripheral pulmonary stenoses may generally be uneventful, because increased pulmonary blood flow in pregnancy may cause little influence on pulmonary circulation in this disease by the same mechanism as in pulmonary stenosis, the course of which is known to be uneventful during pregnancy.

Remarkable improvement of activity by CAPD in a hemodialysis patient with a pseudotumor of the craniocervical junction.

Pseudotumor of the craniocervical junction and destructive spondyloarthropathy (DSA) are the most serious forms of dialysis amyloidosis (DAA). Pain and paralysis due to these lesions significantly impair activity of a patients' daily life (ADL). CAPD improved ADL of a 54 year-old male patient complicated with various forms of DAA after 17 years of hemodialysis (HD) treatment. He was first diagnosed as having carpal tunnel syndrome 12 years after initiation of hemodialysis followed by dialysis shoulders(12 years), trigger fingers(12 years), bone cysts(15 years), tendon ruptures(17 years), DSA and a pseudotumor of the craniocervical junction(17 years). Magnetic resonance imaging (MRI) taken in May 1989 revealed a pseudotumor of the craniocervical junction, which was 30 mm in diameter, located in front of partially destroyed C1 and C2. Neck pain and muscle weakness rendered him bed ridden. Six months after switching to CAPD with administration of prednisolone, neck pain disappeared. He recovered the muscle power by physical rehabilitation. At last it became possible for him to perform the CAPD procedure by himself and drive a car to the hospital as an out patient. In such cases of pseudotumors of the craniocervical junction, CAPD is one of the best methods for relieving the pain and muscle weakness.

[Clinical evaluation of cefotetan in pediatrics].

Cefotetan (CTT), a new cephamycin antibiotic having a long serum half-life (2.93 +/- 0.78 hours), was evaluated for its safety and efficacy in children. Twenty-four patients were treated with a daily dose of 30 to 100 mg/kg of CTT by intravenous administrations mostly in 2 divided doses. The diagnoses of the effective patients were acute bronchitis (5), pneumonia (4), acute urinary tract infections (4), acute enterocolitis (2), presumed septicemia (1), and phlegmon (1); and the effectiveness was 77.3%. The pathogens recovered from these patients were S. pneumoniae (1), H. influenzae (3), S. marcescens (1), E. coli (2), and K. oxytoca (1). CTT was not effective in staphylococcal pneumonia and empyema (each 1 case), in Pseudomonas pneumonia (2), and in a case of brain abscess and mastoiditis of unknown etiology. Diarrhea (2), and transient elevations of the serum GOT, GPT, and LDH (1) were associated with the CTT therapy, but no severe adverse reaction was encountered. The CSF level of CTT seemed to be lower among several new cephalosporins. From the present study, CTT appears to be a safe and effective antibiotic when used in children with susceptible bacterial infections. A twice-a-day schedule was recommended from its long serum half-life.

[Clinical evaluation of cefmenoxime in the pediatric infections].

Cefmenoxime (CMX) was evaluated in 25 children with a suspicion of bacterial infection. Of the 20 confirmed bacterial infections, 19 were cured by CMX therapy (effective rate, 95%). The diagnoses included acute pharyngotonsillitis (4), acute bronchitis (1), pneumonia (7), streptococcal dacryocystitis (1), infections accompanied with acute leukemia (4), and acute urinary tract infections (3). The etiologic pathogens were beta-hemolytic Streptococcus group A (1), and F (1), Staphylococcus aureus (4), Haemophilus influenzae (4), Escherichia coli (4), Klebsiella pneumoniae (2), etc. CMX was very effective for 2 children with respiratory infections due to ampicillin resistant H. influenzae type b. The half life of serum concentration of CMX was 0.76 +/- 0.17 hour after an intravenous bolus injection. A cerebrospinal fluid level of CMX was 5.2 mcg/ml 1 hour after intravenous injection of 1 g (23.8 mg/kg) in a child with inflamed meninges. However this level was not as high as those of cefotaxime, latamoxef, or ceftizoxime measured in the same case. No severe adverse reaction was encountered with CMX therapy. The data suggest that CMX is a safe and effective parenteral antibiotic when used in children with susceptible bacterial infections.

[Cyclocytidine therapy for the herpes-group virus infection in children. A preliminary study].

Cyclocytidine (Cyclo-C) was evaluated as an antiviral chemotherapeutic agent in 10 children with herpes-group virus infections. The diagnoses of the patients were severe cytomegalovirus (CMV) syndrome with pneumonitis in acute leukemia (2), congenital or infantile CMV infections (3), herpes zoster encephalitis in acute leukemia (1), severe nosocomial varicella in compromised patients (2), varicella pneumonia (1) and acute encephalitis due to herpes simplex type-1 (1). Cyclo-C was effective in all the cases with acute infections, although it had no benefit on the course of chronic CMV infection with irreversible damages. However, complete or transient ceasing of viral shedding was obtained in all the 5 cases with CMV infections. From the present small open study, further evaluation of Cyclo-C as an antiviral agent especially in acute CMV infections is warranted.

[Clinical evaluation of ceftizoxime in the pediatric infections (author's transl)].

Ceftizoxime (FK 749, CZX) was evaluated in 24 children with a suspicion of bacterial infection. Of the 17 confirmed bacterial infections, 16 were shown to be effective (effective rate, 94.1%). The diagnosis included acute pharyngitis (2), pneumonia (6), staphylococcal empyema (1), cervical purulent lymphadenitis (2), acute enterocolitis (2), acute pyelonephritis (1), SSSS (1) and suspected septicemia (2). The etiological pathogens recovered were Streptococcus anginosus (1), Streptococcus pneumoniae (1), Staphylococcus aureus (2), Haemophilus influenzae (3), enteropathogenic Escherichia coli (1) etc. A case of suspected Pseudomonas aeruginosa septicemia was not effectively treated with CZX. The serum half-life of CZX was 1.36 hours after intravenous bolus infection. A cerebrospinal fluid level of CZX was 6.2 mcg/ml 1 hour after intravenous bolus injection of 1 g (23.8 mg/kg) in a child with inflamed meninges. No severe adverse reaction was encountered with the CZX therapy. The data suggest that CZX is an excellent candidate for the first choice parenteral antibiotic in the pediatric infections.

[Surgical management of infective endocarditis in childhood].

From 1971 to 1993, four patients, 7 to 13 years of age, underwent intracardiac operation for infective endocarditis. Two patients underwent mitral valve replacements, one was tricuspid replacement and one received tricuspid valvulectomy. There was no operative death but one late death occurred (correction of occurred) due to cerebral bleeding. Surgical treatment of infective endocarditis in childhood could be performed safely by adequate selection of operative methods.