Antithrombin modulates the leukocyte-endothelial cell interaction in the staphylococcal enterotoxin B-challenged mouse.

BACKGROUND: The beneficial effects of antithrombin on endotoxemia are well known. The purpose of this study was to examine the effects of antithrombin in a supertoxin-induced sepsis. METHODS: Mice were injected with staphylococcal enterotoxin B simultaneously with antithrombin. At 1 hour after injection, the mesenteric microcirculation was observed under intravital microscopy. In addition, humoral mediators were measured at the same time. RESULTS: The number of rolling leukocytes on the endothelium was significantly reduced in the treated mice (p < 0.01). The decrease of white blood cell and platelet counts was significantly inhibited in the treated animals (p < 0.01 for both). A comparison of the intercellular adhesion molecule-1 (p < 0.05), soluble tumor necrosis factor-alpha receptor (p < 0.05), and interleukin-6 (p < 0.01) levels showed less increase in the treated mice. CONCLUSION: Antithrombin showed a protective effects on the microcirculation of staphylococcal enterotoxin B-challenged mice by attenuating leukocyte-endothelial cell interaction. Suppression of adhesive molecule expression and cytokine production appears to play roles in this effect.

[Congenital tracheal stenosis due to complete cartilage rings with right pulmonary agenesis].

A 2-month-old male infant with severe dyspnea was diagnosed as having right pulmonary agenesis at birth and was admitted to our hospital after tracheal intubation with an endotracheal tube of 3 mm in diameter. However, the trachea was too stenotic to place the tube in the proper position. Chest X-ray on admission showed pneumonia of the left lung. Preoperative chest computed tomography (CT) scan and bronchoscopy showed that from the level of 12 mm beneath the coricoid cartilage, the trachea tapered and continuing to the tracheal carina and that the smallest tracheal level was located 18 mm distal from the coricoid cartilage, the area of which was 4 mm2. His respiratory condition rapidly deteriorated in spite of intravenous administration of antibiotics and mechanical ventilation. Percutaneous cardiopulmonary support (PCPS) was used to maintain his pulmonary function, and pericardial tracheoplasty was performed. Chest X-ray immediately after the operation did not show left lung reexpansion due to severe pulmonary edema. High-dose steroid pulse therapy was performed, but it was not effective. He died from acute respiratory failure due to infantile respiratory distress syndrome (IRDS) on postoperative day 3. The outcome in this case shows that it is very risky to repair tracheal stenosis in a patient with pneumonia using PCPS.

Jarcho-levin syndrome associated with a complex congenital heart anomaly.

Jarcho-Levin syndrome is characterized by "crab-like" rib cage deformity and multiple vertebral anomalies that cause respiratory failure. Reports of complex congenital heart defects with this syndrome are rare. We describe a female infant with this syndrome and a complex congenital heart defect and review the literature. Congenital heart defects are occasionally complicated by Jarcho-Levin syndrome. Heart defects involving heterotaxic morphology should be included as one of the important clinical features of this syndrome.

The C-terminal domain of thrombospondin-1 induces vascular smooth muscle cell chemotaxis.

OBJECTIVE: Thrombospondin-1 (TSP-1), an acute-phase reactant implicated in vascular disease, is a 420-kd multifunctional glycoprotein chemotactic for vascular smooth muscle cells (VSMCs). TSP-1 has six domains of repeating homologous amino acid sequences: N-terminal, procollagen homology, type 1 repeat, type 2 repeat, type 3 repeat/RGD (T3), and C-terminal (COOH). The purpose of this experiment was to determine which domains of TSP-1 induce VSMC chemotaxis. METHODS: A modified Boyden Chamber chemotaxis assay was used to assess VSMC migration. Serum-free medium, TSP-1, or each of the fusion proteins (10 and 20 microg/mL) synthesized for the different domains were placed in the bottom wells. Quiescent bovine aortic VSMCs (50,000) were placed in the top wells. After 4 hours at 37 degrees C, migrated VSMCs were recorded as cells per five fields (400x) and analyzed with the paired t test. To verify the fusion protein data, we performed chemotaxis assays with antibodies to each of the domains (25 microg/mL) combined with TSP-1 (20 microg/mL) in the bottom wells and VSMCs in the top wells. RESULTS: The COOH domain significantly stimulated VSMC chemotaxis (P = <.001). To a lesser extent, the N-terminal and T3 domains also induced chemotaxis (P <.05). However, only the anti-COOH antibody (C6.7) and the anti-integrin-associated protein portion of COOH antibody (D4.6) significantly inhibited TSP-1-induced VSMC chemotaxis (by 85% and 92%, respectively). CONCLUSIONS: These results implicate the COOH domain as the portion of the TSP-1 molecule primarily responsible for VSMC chemotaxis. This experiment suggests that future strategies in the prevention of VSMC migration, an initial step in the development of vascular lesions, may involve selective inhibition of the COOH domain of TSP-1.

Inhibition of phosphatidylinositol 3-kinase and protein kinase C attenuates extracellular matrix protein-induced vascular smooth muscle cell chemotaxis.

PURPOSE: Intimal hyperplasia (IH), a significant cause of vascular reconstructive failure, is characterized by abnormal vascular smooth muscle cell (VSMC) migration, proliferation, and extracellular matrix (ECM) deposition. The ECM proteins, thrombospondin-1 (TSP-1), fibronectin (Fn), and vitronectin (Vn) can induce VSMC migration; however, the cellular signaling pathways involved are not identical for each ECM protein. Phosphatidylinositol 3-kinase (PI3K) and protein kinase C (PKC) are two enzymes that have been associated with VSMC migration. We sought to elucidate the roles of these enzymes in TSP-1-, Fn-, and Vn-stimulated VSMC migration. METHODS: Chemotaxis assays were performed by using a modified Boyden Chamber. TSP-1, Fn, or Vn (20 microg/mL) or serum-free media (SFM) was placed in the bottom wells of the chamber. Quiescent bovine aortic VSMC were preincubated with LY 294002 (100 micromol/L), a PI3K inhibitor, bisindolylmaleimide I (GF 109203X, 1 micromol/L), a PKC inhibitor, or in SFM alone for 30 minutes. VSMCs (50,000 cells per well) were then placed in the top wells of the chamber, and the assay was conducted for 4 hours at 37 degrees C. Results were recorded as the number of cells migrated per five fields (400x) and analyzed by means of the paired t test, with P value less than.05 considered to be significant (n = 3). RESULTS: The VSMC migration was significantly increased by TSP-1, Fn, and Vn. LY 294002 inhibited TSP-1-, Fn-, and Vn-stimulated VSMC migration (85% to 89%, P <.05). GF 109203X inhibited only TSP-1-stimulated migration (65%, P <.05). CONCLUSION: These results suggest that TSP-1-, Fn-, and Vn-stimulated migration is at least partially dependent on PI3K. However, only TSP-1 stimulated migration is at least partially dependent on PKC.

[Comparison between continuous intravenous and oral administration of 5-FU with LV].

UNLABELLED: In case of 5-fluorouracil (5-FU)/leucovorin (LV) treatment, which is one of the most effective forms of chemotherapy for colorectal carcinoma, 5-FU is usually continuously infused from the venous route. However, since this continuous infusion limits the patients' active daily life, oral administration is preferable. In the present study, we evaluated the efficacy and side effects of orally administered 5-FU/LV. MATERIAL AND METHODS: In the continuous intravenous infusion group (civ group), colon 26 bearing mice were cannulated into central vein from external jugular vein. From this route, either 5, 10, or 20 mg/kg of 5-FU was continuously infused for 7 days (n = 6). In another group, either 10, 20, 40 mg/kg of 5-FU was infused orally (po group, n = 6). The other 6 animals were used for the non-treatment group. In the next series, 100 mg/kg of LV was added for each group above. Tumor volume, thymidylate synthase inhibition rate (TSIR) and body weight were measured at the end of infusion. During the experimental period, mice had free access to chow and water. RESULTS: The tumor/control (T/C) volumes ratio showed that approximately twice the orally administered 5-FU dose had an anti-tumor effect equal to that of 5-FU administered intravenously. Synergic antitumor effects by LV were only revealed in the civ group. Significant body weight loss was recognized only in the po group at a 5-FU dose of more than 20 mg/kg. In summary, since the modulation effect of LV was recognized only with continuously intravenous infusion of 5-FU, further improvement of oral administration is required in the LV/5-FU combination therapy.

Disopyramide improves hypoxia in patients with tetralogy of Fallot through a negative inotropic action.

The hemodynamic and right ventricular volumetric effects of disopyramide were investigated in patients with tetralogy of Fallot (TF). Intracardiac pressure and oxygen saturation were measured, before and after intravenous administration of disopyramide (2 mg/kg) in 7 patients who had not had previous surgery. Right ventricular volume and the diameter of its outflow tract were analyzed in these 7 and in a further 4 patients with a previous shunt. Aortic oxygen saturation increased from 90.4+/-7.5 (mean+/-SD) to 94.1+/-5.5% (p<0.05) with an increase in pulmonary blood flow and pressure. The systolic pressure gradient between the main pulmonary artery and the right ventricle decreased from 59+/-8 to 42+/-9 mmHg (p<0.01). Aortic pressure fell from 77+/-5 to 67+/-4 mmHg (p<0.05). Systemic vascular resistance increased from 15.3+/-2.2 to 19.4+/-3.3 u x m2 (p<0.05). Pulmonary vascular resistance remained unchanged. The diastolic and systolic diameter indices of the right ventricular outflow tract increased from 17.8+/-3.8 to 20.5+/-3.4 and from 6.5+/-3.0 to 10.4+/-2.2 mm/m2, respectively (p<0.01), whereas the right ventricular ejection fraction decreased. Disopyramide improves systemic oxygen saturation in patients with TF through its negative inotropic action on the right ventricle.

Successful stenting of congenital bronchial stenosis in infancy.

UNLABELLED: Recently, stent implantation has become the treatment of choice for patients with tracheobronchial stenosis due to malignant tumours, tuberculosis and recurrent stenosis following lung transplant. However, reports on this procedure in infants with congenital bronchial stenosis are extremely rare. We report successful stent implantation in an infant with congenital left bronchial stenosis followed by rapid improvement in his respiratory condition. CONCLUSION: The use of a stent in infants is still controversial because size mismatch will take place with growth. However, we believe that implantation of a metallic stent can be the preferred treatment of congenital bronchial stenosis even in small infants.

Is early surgery always necessary in patients with aortic valve prolapse complicating an Eisenmenger-type ventricular septal defect?

BACKGROUND: The report presents three patients who showed a typically prolapsed aortic cusp with or without aortic regurgitation associated with a malalignment-type perimembranous defect, the so called Eisenmenger-type ventricular septal defect. RESULTS: Each patient developed spontaneous complete or near closure of the ventricular septal defect without worsening of the aortic regurgitation. CONCLUSIONS: These cases suggest that prolapsed aortic cusp complicating a malalignment perimembranous ventricular septal defect is not always an absolute indication for early surgery to prevent progressive aortic regurgitation.

[Somatic mosaicism of p(CTG)n expansion in a case of myotonic dystrophy with parotid tumor].

Myotonic dystrophy (MD) is an autosomal dominant systemic disorder with an unstable expansion of the CTG triplet repeat in the 3'-untranslated region of the gene encoding myotonine protein kinase (DMPK) which maps to chromosome 19q13.3. Somatic mosaicism of CTG repeats in MD has been reported; and it has been observed that CTG repeats in tumor tissues associated with MD are more expanded than the other tissues. It is not rare that parotid tumors are found in patients with MD. We performed Southern blot analysis for tissues from the parotid tumor, the normal parotid gland, the skeletal muscles, and the leukocyte from a 60-year-old patient with MD. CTG repeat was most expanded in the parotid tumor, and the normal parotid gland had longer expansion of CTG repeat than the skeletal muscles. The leukocyte had the shortest expansion of CTG repeat. The expansion of CTG repeat in the parotid tumor may be related to active cell division and may underlie the occurrence of tumors in MD.

Diet and lifestyle guidelines and desirable levels of risk factors for the prevention of diabetes and its vascular complications in Indians: a scientific statement of The International College of Nutrition. Indian Consensus Group for the Prevention of Diabetes.

BACKGROUND: There has been a rapid increase in the prevalence of diabetes and cardiovascular disease in India, in association with rapid changes in diet and lifestyle. In adults, the prevalence of diabetes, hypertension and coronary artery disease is two- to threefold greater in the urban population than in rural populations; it is associated with modest insulin resistance in urban groups. METHODS: In response to a proposal by the International College of Nutrition that specialist experts should develop consensus recommendations for the prevention of chronic diseases, Indian specialists in diabetes and vascular disease have collaborated to produce guidelines relevant to the population of India. RECOMMENDATIONS: Because Indian urban populations have a modest increase in overweight and low rates of obesity in association with the rapid emergence of diabetes and cardiovascular risk, a body mass index of 21 kg/m2 should be considered safe, with a range of 19-23 kg/m2 acceptable; > 23 kg/m2 should be considered overweight, and > 25 kg/m2 should be taken to indicate obesity. A waist:hip ratio > 0.88 in males and > 0.85 in females should be considered to indicate central obesity, because the prevalence of coronary disease, hypertension and associated disturbances of insulin resistance are more common above these limits. For the prevention of vascular disease, there is general international consensus that the desirable serum concentration of cholesterol should be < 170 mg/dl (> 4.42 mmol/l), which may also be optimal for Indians; values between 170 and 200 mg/dl (4.42-5.2 mmol/l) should be considered borderline. The critical values for low density lipoprotein cholesterol may be < 90 mg/dl (ideal), 90-110 mg/dl (borderline high) and > 110 mg/dl (high) (< 2.32, 2.32-2.84 and > 2.84 mmol/l, respectively). Fasting triglycerides should be < 150 mg/dl (< 1.69 mmol/l) and high-density lipoprotein cholesterol > 35 mg/dl (> 0.9 mmol/l). The limit for the total energy derived from fat intake should be < 21%/day (7% each for saturated, polyunsaturated and mono-unsaturated fatty acids). The carbohydrate intake should provide more than 65% of daily energy, mainly from complex carbohydrates. A daily dietary intake of 400 g fruits, vegetables and legumes, 400 g cereals, in conjunction with 25 g soya bean or mustard or canola oils (rich in n-3 fatty acids) in place of fats rich in saturated fat, may be protective against diabetes and vascular disease. Moderate physical activity with the aim of burning 300 Kcal/day (> 1255 KJ/day), and cessation of tobacco and alcohol consumption, may provide an effective programme for prevention of diabetes and its vascular complications in Indians.

Medium-term results of percutaneous transluminal balloon aortic valvuloplasty with Inoue balloon catheter for congenital aortic stenosis.

Although percutaneous transluminal balloon aortic valvuloplasty (PTAV) has been performed for congenital aortic stenosis in infants and children for several years, its efficacy and the associated aortic regurgitation (AR) have not been widely discussed. Percutaneous transluminal balloon aortic valvuloplasty using an Inoue balloon catheter was performed for congenital aortic stenosis in 12 patients (4-16 years old) in this study. The systolic aortic valve pressure gradient ranged from 42 to 111 mmHg before PTAV and became < 50 mmHg immediately after PTAV in 10 cases (83%). Eight of these 10 patients had no increase in the gradient during subsequent observation for a period of 9-40 months. Aortic regurgitation increased immediately after PTAV in nine cases (75%). It increased from grade 1 to grade 2 in eight cases and from grade 1 to grade 3 in one patient; no significant enlargement of the left ventricular end-diastolic diameter and no significant change in the left ventricular end-diastolic pressure (LVEDP) or the cardiac index was observed during follow-up in these patients. There was a correlation between the diameter of the balloon and efficacy; an appropriate diameter was considered to be about 90% of the aortic annular diameter. Changes in the hemodynamic parameter after PTAV with an Inoue balloon were small in most patients and this procedure is considered to be a treatment that should be attempted prior to surgery for congenital aortic stenosis.

[A case of fibromuscular dysplasia presenting with Wallenberg syndrome, and developing a giant aneurysm of the internal carotid artery in the cavernous sinus].

A 25-year-old man developed Wallenberg syndrome (WS). At that time his carotid angiography was normal. When he was 28 years old, he suffered from retinal artery embolism in the left eye. At the age of 30 years, he had an acute onset of abducens nerve palsy in his right eye. The carotid angiography showed a giant aneurysm at the cavernous sinus portion in the right internal carotid artery. At his age of 38, the right oculomotor, trochlear and trigeminal nerves were involved. A vertebral angiography revealed a bead-like formation, and a diagnosis of fibromuscular dysplasia (FMD) was made. An intensive angiographic examination revealed many stenotic or dilated lesions in the carotid, vertebral, coronary, renal, and hepatic arteries. A sural nerve biopsy specimen revealed that the sural vein was involved. In Japan only one case of FMD presenting with WS is known. FMD should be under consideration as an underlying disease, when WS occurred in younger patients with few risk factors. In this patient an angiography revealed no abnormality in the cavernous sinus portion of the internal carotid artery, when he suffered from WS. However, eight years later he was proved to have a giant aneurysm in the cavernous sinus portion. In conclusion, we support the hypothesis that aneurysm may originate from angiographically normal arterial wall in FMD.

Postoperative bronchopleural fistula: clinical and experimental study.

It is a well-known fact that in pulmonary tuberculosis patients treated by resection, the quality of the suture material used for closing the bronchial stump plays an important role in the pathogenesis of postoperative bronchopleural fistula. Of 426 cases treated surgically and in whom silk suture thread was used, 23 developed bronchopleural fistula, whereas none of the 220 cases sutured with nylon monofilament developed abnormality. Statistical analysis of 100 surgical cases with silk thread suture and of 100 cases with nylon monofilament suture showed that the two groups had no marked differences as to background factors. Howevers, as compared with the silk-thread suture group, the nylon-monofilament suture group revealed more consistently favorable postoperative bronchoscopic findings. Experimental studies with dogs showed a similar lack of complications when the monofilament suture material was used, as contrasted were conducted in hospital by the same surgical personnel using the same procedures, it can be said that, to insure prevention of complications, the suture material for bronchial stump closure should be of non-irritating nature and preferably of monofilament strength and quality, such as nylon monofilament.