Plasma fibrinogen and D-dimer concentrations are associated with the presence of abdominal aortic aneurysm: a systematic review and meta-analysis.

OBJECTIVES: To summarise the present evidence for an association between circulating fibrinogen or D-dimer and presence of abdominal aortic aneurysm (AAA) presence. DESIGN: MEDLINE database was searched to identify all case-control studies that compared plasma fibrinogen or D-dimer concentrations between patients with AAA and subjects without AAA. For each study, data regarding fibrinogen or D-dimer concentrations in both the AAA and control groups were used to generate mean differences (MDs) and 95% confidence intervals (CIs). Study-specific estimates were combined using inverse variance-weighted average of logarithmic MDs in both fixed- and random-effects models. RESULTS: Our search identified 10 eligible studies including 834 cases with AAA and 6971 controls without AAA for fibrinogen and six studies including 264 patients with AAA and 403 subjects without AAA for D-dimer. Pooled analysis demonstrated significantly higher fibrinogen (fixed-effects MD, 0.37gl(-1); 95% CI: 0.30-0.44gl(-1)) and D-dimer (random-effects MD: 415.36ngml(-1); 95% CI: 128.97-701.76ngml(-1)) concentrations in the AAA group than those in the control group. CONCLUSIONS: We found that plasma fibrinogen and D-dimer concentrations are likely to be higher in cases with AAA than control subjects. Higher plasma fibrinogen and D-dimer concentrations may be associated with the presence of AAA.

Two-stage portal vein ligation facilitates liver regeneration in rats.

BACKGROUND/AIMS: Recent reports have demonstrated that some patients are unable to undergo scheduled liver resection after preoperative portal vein embolization due to insufficient hypertrophy of the future remnant liver. The present study examined whether two-stage portal vein ligation (PVL) increases hypertrophy of the future remnant liver compared to conventional PVL in rats. METHODS: Rats were divided into 3 groups: group A, ligation of left primary branch; group B, ligation of right and left primary branches; group C, ligation of the left primary branch, followed by 2-stage PVL 7 days postoperatively. To evaluate liver regeneration, the proliferating cell nuclear antigen labeling index (LI), mitotic index (MI) in the caudate lobe and weight ratio of caudate lobe to body weight were measured. RESULTS: The weight ratio of caudate lobe to body weight was significantly higher in group C than in groups A or B 14 days postoperatively. In groups A and B, LI and MI in the caudate lobe peaked 2 days postoperatively, then decreased to preoperative levels by 7-8 days postoperatively, but remained significantly elevated until 10-14 days postoperatively in group C. CONCLUSION: Two-stage PVL increases hypertrophy of the future remnant liver compared to conventional PVL in rats.

Ruptured cerebral aneurysms treated by stent-assisted GDC embolization--two case reports with long-term follow-up.

Two cases of acutely ruptured cerebral aneurysm of low dome/neck ratio treated by stent-assisted GDC embolization using balloon-expandable coronary stent, and also their long-term follow-up results are reported. After embolization, the basilar trunk aneurysm was completely occluded, and partial occlusion was obtained for the internal carotid (IC)-paraclinoid aneurysm. Oral ticropidine (200 mg/day) was given after the embolization, and no neurological events were seen during long-term follow-up (64-68 months). Follow-up angiograms of the basilar trunk aneurysm at 20 months showed complete occlusion and no in-stent stenosis. Follow-up angiograms of the IC-paraclinoid aneurysm at 52 months showed complete occlusion of the aneurysm, but mild stenosis at the distal end of the stent graft. These cases suggested that stent-assisted GDC embolization is effective for prevention of rebleeding from ruptured aneurysm during long-term observation even with sufficient dose of antiplatelets therapy. Caution should be taken on aneurysmal recanalization and parent artery stenosis due to stent deployment during long-term period.

Isolation and some biochemical characteristics of nuclei from AH-66 hepatoma cells.

Cetylpyridinium chloride uniquely facilitated the isolation of nuclei from AH-66 hepatoma ascites cells in an isotonic medium without homogenization because of its strong solubilization of their plasma membranes, which were resistant to mechanical shearing with the commonly used nonionic detergents such as Triton X-100, Nonidet P-40, and Tween 80. Virtually all the nuclei in a population of AH-66 cells (10(6)/ml) can be isolated with 0.2% cetylpyridinium chloride. The isolated nuclei were free of adherent cytoplasm, maintained satisfactory morphology, and had high activity of nicotinamide adenine dinucleotide pyrophosphorylase. Two-dimensional polyacrylamide gel electrophoresis of the acid-soluble nuclear proteins of the AH-66 hepatoma nuclei isolated by the cetylpyridinium chloride procedure as well as by the citric acid procedure revealed that Spots Ac and C16-C18 were significantly intense in the gel pattern. Unexpectedly, Spot A10 was absent from the gel pattern of AH-66 hepatoma nuclei.

Superoxide assay-leukocyte adherence inhibition test and a soluble factor which stimulates the adherence of macrophages.

A modified method for the leukocyte adherence inhibition test is described. Peritoneal cells from immune guinea pigs or peripheral mononuclear cells from cancer patients were incubated with immunizing antigen or tumor extract in a 4-mm-wide glass microcell for spectrophotometer analysis. Instead of visual cell counting, the cells adherent to the bottom of the microcell were stimulated with cytochalasin E and wheat germ agglutinin, and the amount of the superoxide (O2.-) generated from the adherent macrophages or monocytes was assayed. Antigen-specific adherence inhibition of peritoneal cells of the immunized guinea pigs was detected 2 weeks after immunization. In contrast, cell adherence was stimulated after 3 weeks. It was shown that a soluble factor was responsible for the adherence stimulation and that nonadherent cells were necessary for its production. Peripheral mononuclear cells of 70% of the tumor-bearing lung cancer patients reacted to the lung tumor extract (9 adherence inhibitions and 7 adherence stimulations per 23 patients). Twenty-five % (3 of 12) of tumor-free patients showed positive reactions, all with adherence stimulation. Of the 12 healthy donors, 3 cases of pneumonia, one case of angiosarcoma of the left flank, one case of hemangiopericytoma of the mediastinum, and 8 cases of breast cancer, non reacted with the lung tumor extract, and only one of 7 lung tuberculosis patients showed positive adherence stimulation.

Nonspecific adjuvant immunotherapy of lung cancer with cell wall skeleton of Mycobacterium bovis Bacillus Calmette-Guérin.

Nonspecific adjuvant immunotherapy with Bacillus Calmette-Guérin cell wall skeleton (BCG-CWS) was given to 155 lung cancer patients. Clinical effects of the BCG-CWS treatment were estimated by comparing the survival of the BCG-CWS group with that of a historical control group on the basis of 4-year results. Significant prolongation of survival time has been observed in Clinical Stages II, III (M0) and III (M1). However, most Stage III patients who were given the BCG-CWS treatment died of cancer itself after marked prolongation of survival time. An increase in complete cure rate has been expected only in Stages I and II. Surgicopathological staging was used in resected cases. Resected cases at any stage were sensitive to treatment with BCG-CWS. Histologically, all types of lung cancer including squamous cell carcinoma, adenocarcinoma, and anaplastic carcinoma were sensitive to treatment with BCG-CWS. Intrapleural administration of BCG-CWS to patients with malignant pleurisy was effective in controlling the pleural effusion and prolonging the survival time. No serious complication has been experienced in our study.

Alkali-labile oligosaccharide units of a sialoglycoprotein from rabbit erythrocyte membranes.

Two glycoproteins (apparent molecular weights 120,000 and 70,000) were extracted from rabbit erythrocyte membranes, and only one (Mr 120,000), which is a sialoglycoprotein, contained O-glycosidically linked sugar chains. Alkali-labile oligosaccharide units of the sialoglycoprotein were released as reduced oligosaccharides by NaOH-NaB3H4 treatment, and then purified by gel filtration on a Bio-Gel P-4 column followed by ion-exchange chromatography. From the results of methylation analysis, mass spectrometry and chromium trioxide oxidation, the main oligosaccharide unit was determined to be a linear trisaccharide (85% by weight), NeuNGc alpha(2----3)Gal beta(1----3)GalNAcol. In addition, small amounts of a tetrasaccharide (11% by weight) and a disaccharide (4% by weight) were found, which were determined to have the following structures, NeuNGc alpha(2----3)Gal beta(1----3)[NeuNGc alpha(2----6)] GalNAcol and Gal-GalNAcol, respectively.

Vitamin E protects against polymorphonuclear leukocyte-dependent adhesion to endothelial cells.

We evaluated the effects of alpha-Toc on surface expression of CD11b/CD18 on polymorphonuclear leukocytes (PMN) stimulated with N-formyl-methionyl-leucyl-phenylalanine (fMLP) and oxidized low-density lipoprotein (oxLDL). Incubation of PMN with fMLP (1 microM) or oxLDL (100 microg/mL) increased CD11b/CD18 expression; pretreatment with alpha-Toc reduced in a dose-dependent manner. PMN obtained from healthy adults ingesting 600 mg alpha-Toc per day for 10 days were similarly incubated with fMLP or oxLDL; the surface level of CD11b/CD18 was inversely correlated with serum alpha-Toc concentrations. Adherence of PMN to human umbilical vein endothelial cells was increased by fMLP or oxLDL stimulation but reduced by alpha-Toc pretreatment or anti-CD18 monoclonal antibodies. cAMP-dependent protein kinase (PKA) and protein kinase C (PKC) activity in PMN was also assayed. A PKC inhibitor, but not a PKA inhibitor, suppressed CD11b/CD18 up-regulation, and alpha-Toc slightly decreased fMLP- and oxLDL-induced activation of PKC. These results suggest that alpha-Toc may prevent inflammation by both reducing CD11b/ CD18 up-regulation and decreasing PMN-dependent adherence to EC.

Assessment of severity of cardiac rejection in heterotopic heart transplantation using indium-111 antimyosin and magnetic resonance imaging.

Seven canine donor hearts in which atrial septal defect and tricuspid regurgitation had previously been produced were heterotopically transplanted into the recipients' chest cavities. Indium-111 antimyosin myocardial imaging of the excised heart was performed using a scinticamera. Magnetic resonance imaging was also performed and the T2 relaxation time calculated. Subsequently, these data were correlated with pathological findings, which indicated the degree of rejection. Indium-111 antimyosin uptake was high in moderate and severe rejection, but the T2 relaxation time was prolonged even in mild rejection. Thus indium-111 antimyosin uptake was specific, and the T2 relaxation time was sensitive, for detecting the severity and extent of cardiac rejection. Although ex vivo experimental results have been reported, these new methods allow characterisation and accurate evaluation of myocardial tissue undergoing cardiac rejection.

Sodium nuclear magnetic resonance imaging of acute cardiac rejection in heterotopic heart transplantation.

Nuclear magnetic resonance (NMR) imaging was used to measure tissue sodium-23 in the myocardium undergoing cardiac rejection. In six dogs, the donor heart was heterotopically transplanted into the recipient's chest cavity. The dogs were then killed and sodium-23 images of the excised hearts were obtained using a high field (1.5 Tesla) NMR imaging system. Proton NMR imaging of each excised heart was also performed and T1, T2 relaxation times were calculated. Subsequently, these data were correlated with pathological findings of mild, moderate and severe rejection. The correlation coefficients between the rejection score and the T1, T2 relaxation times and sodium NMR signal intensity were 0.79, 0.70 and 0.84, respectively. Severely rejected areas of the myocardium were visualised by increased sodium NMR signals. These findings suggest that an increase of sodium NMR intensity is mainly caused by an increase of intracellular sodium content due to irreversible myocardial necrosis. Sodium NMR allows evaluation of the location and extent of rejection of myocardium after heart transplantation.

New bronchodilators. 1. 1,5-Substituted 1H-imidazo[4,5-c]quinolin-4(5H)-ones.

A series of novel xanthine-based tricyclic heterocycles in 1H-imidazo[4,5-c]quinolin-4(5H)-ones was designed, synthesized, and tested as potential active bronchodilators. Inhibition of the Schulz-Dale (SD) reaction-induced contraction in trachea and inhibition of antigen inhalation-induced bronchospasm in passively sensitized guinea pigs served as primary in vitro and in vivo assays, respectively. Simultaneous measurement of acute lethal toxicity (minimum lethal dose; MLD, po) in mice allowed determination of a safety margin. The bronchodilatory activity of these heterocycles was considerably varied with the nature of substituents at the 5-position. The most active substituents at the 2- and 5-positions and on the aromatic ring were found to be hydrogen, n-butyl, and hydrogen, respectively. There was a bulk tolerance for lipophilic substituents at the 1-position. 5-Butyl-substituted compounds appeared to be less toxic than theophylline on the basis of MLD data. Thus 5-butyl-1-methyl-1H-imidazo[4,5-c]quinolin-4(5H)-one (10) (IC50 value of the SD assay = 0.25 microM, MLD > 300 mg/kg) was selected for further studies. Compound 10 (KF15570) reduced bronchoconstriction produced by antigen (Konzett-Rössler preparation in anesthetized guinea pigs, ED50 = 0.42 mg/kg, iv) more effectively than aminophylline (ethylenediamine salt of theophylline, ED50 = 7.8 mg/kg, iv) but had fewer side effects on the heart and CNS than theophylline. Compound 10 and its derivatives showed weak adenosine antagonism and phosphodiesterase (PDE) inhibition which could not account for their potent bronchodilation. Although their precise mechanism of action remains unclear, this series of novel tricyclic heterocycles represents a new class of bronchodilator.

New bronchodilators. 3. Imidazo[4,5-c][1,8]naphthyridin-4(5H)-ones.

In order to develop new oral bronchodilators, a series of novel imidazol[4,5-c][1,8]naphthyridin-4(5H)-ones 5 were designed and synthesized. Some of these new heterocycles exhibited more potent bronchodilator activity in vitro and in vivo than theophylline. With respect to modification at the 5-position, both phenyl and n-butyl substitution produced potent activity. Though bulk tolerance at N-3 is observed with short and small lipophilic groups, any substitution at the other positions and transformations of the parent skeleton eliminated activity. Thus 5-phenyl-1H-imidazo[4,5-c][1,8]naphthyridin-4(5H)-one (23) (KF17625), which satisfied these conditions, was selected for further studies (antigen inhalation-induced bronchospasm model; minimum effective dose (MED) = 1 mg/kg, po; antigen-induced contraction of trachea (the Schultz-Dale reaction), IC50 = 2.2 microM). Compound 23 inhibited carbachol-, histamine-, or leukotriene D4-induced contraction and relaxed spontaneous tone in guinea pig isolated tracheal preparations with, 4- to 16-fold greater potency than aminophylline. Thus it appeared to relax directly the airway smooth muscle. 23 did not have any influence on adenosine binding at 10 microM, but inhibited canine tracheal phosphodiesterase (PDE) IV (IC50 = 12 microM) and concanavalin-A-induced histamine release from rat mast cells (44% inhibition at 10 microM). Although the detailed mechanisms of these compounds remain to be elucidated, this series of novel tricyclic heterocycles represents a new class of bronchodilator.

Usefulness of left ventricular volume in assessing tetralogy of Fallot for total correction.

Ninety-one patients with tetralogy of Fallot underwent intracardiac repair between 1978 and 1981. One patient died from left-sided heart failure. Retrospective analyses of this death revealed a significant decrease of the left ventricular (LV) end-diastolic volume index (EDVI) of 21 ml/m2 (36% of normal). Results of early postoperative hemodynamic studies after total correction of this anomaly suggested that an EDVI of 30 ml/m2 is the minimal requirement for adequate cardiac output postoperatively. Based on these data, 3 patients with decreased LV volume with EDVI of around 30 ml/m2 were challenged with the primary repair with success, although they required atrial pacing and catecholamine support postoperatively to maintain adequate left atrial pressure and cardiac output. From these results, it is recommended that patients with tetralogy of Fallot and an EDVI of 30 ml/m2 or more can be considered as candidates for the primary repair, but that patients with an EDVI of less than 30 ml/m2 should be palliated once by systemic-to-pulmonary arterial shunt procedures. Subsequent total correction should be performed after sufficient LV growth for those patients.

The criteria for reconstruction of right ventricular outflow tract in total correction of tetralogy of Fallot.

Retrospective analysis was undertaken to determine the influence of residual pulmonary stenosis and surgically induced pulmonary insufficiency on the operative mortality rate in 104 patients with tetralogy of Fallot who underwent total correction between 1967 to 1970 at First Department of Surgery, Osaka University Hospital. This study revealed that, in order to improve the operative outcome in this anomaly, it is necessary to correct pulmonary stenosis to the point of the right-to-left ventricular peak pressure ratio (PRV/LV) less than 0.8 as well as preventing severe pulmonary insufficiency. Through this study, the criteria for enlargement of the right ventricular outflow tract (RVOT) for each given body size which will produce a PRV/LV of less than 0.8 were derived in 1971. If the size of the RVOT after infundibulectomy and valvotomy is smaller than that prescribed by the criteria, an outflow patch must be placed on the pulmonary outflow tract. Since 1971, these criteria have been used in total correction of this anomaly in our affiliated hospital without any problem and have been yielding good operative results. Postoperative hemodynamic studies have shown that our criteria are suitable.

Trans-pulmonary arterial closure of ventricular septal defect.

Fourteen patients ranging in age from 4 months to 28 years underwent closure of a ventricular septal defect (VSD) through the pulmonary valve after pulmonary arteriotomy. In 13 of these the VSD was of the supracristal type and in one patient it was of the bulboventricular type. In all patients, including two infants whose VSD was closed under circulatory arrest, the operative and postoperative courses were uneventful except in one, who needed prolonged respiratory care. Right bundle branch block (RBBB) resulted in four patients, one of whom had a bulboventricular defect. The procedure is technically feasible without difficulty when the VSD is of the supracristal type and when the patient is too small. Trans-pulmonary arterial closure is the method of choice for treating a supracristal VSD, as this procedure leaves no postoperative right ventricular scar. However, the advisability of continuing to use this procedure is to be decided after statistical analysis of the frequency of postoperative RBBB can be made with a larger series of patients.

Carbohydrate and lipid metabolism in open-heart surgery.

Carbohydrate and lipid metabolism was studied in 8 patients who underwent open-heart surgery with the aid of extracorporeal circulation. Hyperglycemia was observed during perfusion. Despite the high glucose levels during perfusion, insulin responses were depressed. A rise of insulin levels was observed one hour after perfusion, and at the same time the glucose levels dropped. Suppression of insulin secretion during perfusion may be the result of increased catecholamine secretion, induced hypothermia, or heparin administration. High levels of non-esterified fatty acids (NEFA) and low levels of triglycerides were observed immediately before, during, and after perfusion while heparin was being utilized. This phenomenon was considered to be strongly affected by the use of heparin. The levels of growth hormone were depressed during perfusion but significantly elevated one hour after the end of perfusion. These phenomena may be caused by the fluctuations in glucose and NEFA levels.

Long-term circulatory maintenance with a left-sided single artificial heart.

The purpose of this study is to examine the feasibility of long-term circulatory maintenance with only a left-sided single artificial heart that is inserted between the left atrium and the aorta to assist a nonfunctioning heart. The basic hemodynamics were determined in short-term experiments in goats (n = 4), and feasibility studies of long-term circulatory maintenance with a single artificial heart during cardiac arrest were performed in long-term experiments (n = 12). When pulmonary vascular resistance was less than 15,000 dynes .sec.cm-5.kg, which was twice the normal value, the circulation was well maintained with the single artificial heart alone, so long as the right atrial pressure was kept at 14 to 16 mm Hg. Under such conditions the flow yielded by the single artificial heart fluctuated between 80 and 140 ml/kg/min depending on the animal's demand, while the mean arterial pressure was kept above 80 mm Hg. The goats behaved normally, although retention of pleural effusion was a serious problem in maintaining normal circulation over a long-term. Maintaining the plasma total protein level above 6.0 gm/dl delayed the onset of retention or even prevented pooling of pleural effusion. The longest survival period to date has been 38 days. We conclude that when the pulmonary vascular resistance is less than twice the normal value and the total protein level is above 6.0 gm/dl, a left-sided single artificial heart alone can maintain normal circulation and provide time for patients with a nonfunctioning heart to undergo a further treatment, such as heart transplantation.

Surgical treatment of giant left atrium combined with mitral valvular disease. Plication procedure for reduction of compression to the left ventricle, bronchus, and pulmonary parenchyma.

Giant left atrium associated with mitral valvular disease frequently produce postoperative problems with regard to hemodynamical and respiratory management. A new procedure of para-annular and superior plication combined with the conventional right-side plication with trimming of the left atrial wall was devised to relieve compression induced by the giant left atrium. A total of 40 patients with giant left atrium underwent operation. Ten had the valvular procedure only and 30 had the valvular and plication procedures. The plication procedure resulted in a significant decrease in the incidence of low-output syndrome and respiratory failure postoperatively, as well as a marked decrease in mortality. We conclude that the plication procedure is an effective means of relieving compression in the presence of giant left atrium.

Intraventricular repair of single ventricle associated with transposition of the great arteries.

Intraventricular repair was performed successfully in a 6-year-old body having a ventricle associated with d-loop and d-transposition in situs solitus of the atria and viscera. A spiral Teflon patch was utilized to partition the ventricle. Complete heart block did not result, and the patient is doing well 8 months after the operation. Details of the pre- and postoperative studies, as well as details of the surgical technique, are presented. A review is presented of the operative procedures that have been designed for the correction of a single ventricle associated with transposition of the great arteries and have been reported previously in the literature. The advantages for use of the techniaue employed in the present case are discussed.