The Chemical Protecting Group Concept Applied in Crosslinking of Natural Tissues with Glutaraldehyde Acetals

This work describes the results of the controlled crosslinking of collagen matrices by glutaraldehyde based on a double protection strategy, glutaraldehyde acetals and lysine protonation due to the acidic conditions of acetal formation. Materials crosslinked by this approach were characterized by thermal stability comparable to those obtained by conventional procedures with mechanical properties expected for bioprosthesis manufacture and with a higher stability toward collagenase hydrolysis. The integrity of the microfibrillar structure was confirmed by optical and scanning electronic microscopy. The results indicate that the glutaraldehyde acetals procedure may be of potential use for the crosslinking of bovine pericardium used in the manufacture of bioprosthetic devices. Advantages may be related to the production of materials with homogeneous crosslinking distributions, associated with better definition in the nature of the chemical link that they introduce, due to a better distribution of glutaraldehyde within the tissue matrix before the crosslinking reaction is allowed to occur. As a result, materials with improved biological and mechanical properties are expected.     

Mechanisms underlying the enhanced elevation of IL-1beta and TNF-alpha mRNA levels following endotoxin challenge in rat alveolar macrophages cultured with low-Mg2+ medium.

We have previously shown that interleukin (IL)-1beta and tumour necrosis factor (TNF)-alpha mRNA levels in rat alveolar macrophages are increased in by endotoxin (lipopolysaccharide; LPS)- stimulation and further enhanced by culturing with low-Mg2+ medium. We have now investigated the mechanisms of underlying this enhancement by using some specific signal transduction inhibitors. The enhanced elevation of both mRNAs levels was suppressed by pretreatment with TMB-8 (which inhibits calcium release from the endoplasmic reticulum) or dexamethasone (which inhibits nuclear factor [NF]-kappaB and activator protein [AP]-1), but not with verapamil or nifedipine (which inhibits calcium channels). The enhancment of IL-1beta, but not TNF-alpha mRNA levels, was suppressed by pretreatment with W-7 (which inhibits calmodulin), whereas the enhancement of TNF-alpha mRNA levels was suppressed by pretreatment with U73122 (which inhibits phospholipase C). Curcumin (an inhibitor of AP-1), suppressed the increases in both mRNAs induced by low-Mg2+ medium alone, but had no suppressive effect on the levels of either mRNA after LPS-stimulation in low-Mg2+ medium. Pyrrolidine dithiocarbamate (an inhibitor of NF-kappaB) prevented the elevation of TNF-alpha mRNA levels induced by low-Mg2+ medium without LPS-stimulation, but had no suppressive effect on IL-1beta mRNA levels. From these results, we conclude that the enhanced elevation of IL-1beta and TNF-alpha mRNA levels seen in LPS-stimulated alveolar macrophages in low-Mg2+ medium occurs partly via the same, and partly via different, signaling pathways.     

Lateral position prevents respiratory occlusion during surgical procedure under general anesthesia in the patient of huge anterior mediastinal lymphoblastic lymphoma

Lymphoblastic lymphoma, an aggressive mediastinal mass, is recognized as serious threat to the patient in developing cardiac tamponade or airway obstruction. Surgical procedure is often required to relieve clinical emergency and to establish prompt pathological diagnosis. However, in such a patient, acute respiratory occlusion in the spine position can be a life-threatening complication during general anesthesia. We describe a 17-year-old man whose cardiac tamponade was treated by pericardial-pleural window through a left anterior thoracotomy in the lateral position. The patient recovered from hemodynamic compromise without showing respiratory occlusion during general anesthesia and remained in the lateral position until extubation. Pathological diagnosis was precursor T-lymphoblastic lymphoma. There were no complications attributable to the operative procedure. Further chemotherapy reduced the mediastinal mass in size after two weeks when the patient developed sepsis and died. Lateral position prevents respiratory occlusion during surgical procedure under general anesthesia in the patient of huge anterior mediastinal tumor with airway obstruction.     

Plasma carnitine concentrations in patients undergoing open heart surgery.

Carnitine is an essential cofactor for fatty acid (FA) metabolism, the predominant source of ATP in the normal aerobic heart. During myocardial ischemia, FA metabolism is impaired and tissue carnitine levels are depleted. Since the heart cannot synthesize carnitine, plasma carnitine could play an important role in maintaining myocardial carnitine levels during reperfusion. The purpose of this study was to determine the incidence of abnormal plasma carnitine concentrations in open heart surgery. Blood samples were obtained from eleven patients before, immediately after, and two hours after cardiopulmonary bypass (CPB). Total and free carnitine levels were significantly reduced immediately after CPB (p<0.01) and remained depressed until two hours after CPB (p<0.01 vs. pre CPB), while acyl carnitine levels were unchanged over the course of this study. These depressed free carnitine levels might affect cardiac metabolism in the heart after open heart surgery. Carnitine supplement might be a useful adjunct in the therapy after open heart surgery.     

A case of mixed connective tissue disease successfully treated for hemophagocytic syndrome with intermittent intravenous injection of cyclophosphamide]

A 52 year-old woman noticed general fatigue, polyarthralgia, and muscle weakness of lower extremities in October 2001. In December, she felt difficulty in walking due to muscle weakness. In January 2002, she admitted another hospital because of dyspnea on exertion and edema of lower extremities. Laboratory test revealed leukocytopenia, the elevation of creatine kinase and positive anti-U1-RNP antibodies. Her chest computed tomography (CT) showed severe interstitial pneumonia. Cardiac echogram revealed that she had pericardial effusion and pulmonary hypertension. Then she was transferred to Keio University Hospital and she was diagnosed as having mixed connective tissue disease (MCTD) manifestating myositis, interstitial pneumonia, pulmonary hypertension and pericarditis. Prednisolone (PSL) 60mg daily following to methylprednisolone (mPSL) pulse therapy was begun and her symptoms were gradually improved. In middle of February, she complained of high fever over 39.0 degrees C. Bacterial culture tests were negative and laboratory data indicated pancytopenia and a high level of serum ferritin. Bone marrow aspiration revealed hemophagocytosis in bone marrow specimens and she was diagnosed as having hemophagocytic syndrome associated with MCTD. mPSL pulse therapy was not effective and intermittent cyclophosphamide pulse therapy (IV-CY) was performed resulting in improvement of the symptoms. This case suggested the effectiveness of IV-CY therapy in patients with corticosteroid-resistant HPS associated with connective tissue diseases.     

Effect of intermittent parathyroid hormone (1-34) treatment on the bone response after placement of titanium implants into the tibia of ovariectomized rats.

PURPOSE: This study investigated the effect of parathyroid hormone (1-34) [PTH(1-34)] on bone reactions after tibial placement of titanium screw implants into ovariectomized rats. MATERIALS AND METHODS: Twelve-week-old female Wistar rats were divided into 3 groups of 24. The first group (Sham group) was sham-operated; the second group (OVX group) was ovariectomized only; and the third group (PTH group) was subcutaneously administered 30 microg/kg PTH in the dorsal region 3 days per week starting the fourth week after ovariectomy until the end of the experiment. Titanium screw implants were placed in the proximal metaphysis of the tibia of all 3 groups at 168 days after surgery. The animals were killed 7, 14, 28, and 56 days after implantation. Undecalcified sections were prepared and evaluated by light microscopy. Histomorphometric measurements were obtained using a computer-based image analyzer to quantify the unit bone mass around the implant and the rate of implant-bone contact. RESULTS: When PTH administration was started 21 days after ovariectomy, the volume density of bone around implants in the PTH group was almost the same as that of the Sham group throughout the entire observation period. This finding suggests that not only can intermittent human PTH(1-34) administration prevent resorption of newly generated trabeculae around an implant but also it can aid in the recovery of bone volume lost due to ovariectomy. CONCLUSION: When dental implants are applied to jaw bone showing trabecular bone loss, it may be possible to increase bone density around an implant by intermittent human PTH(1-34) administration and thereby improve clinical results.     

A case of autoimmune pancreatitis complicated with immune thrombocytopenia]

A 80-year old man was referred to our hospital because of an elevation of serum amylase level. Diffuse enlargement of the pancreas was detected by abdominal computed tomography, and also diffuse narrowing of the main pancreatic duct was revealed using endoscopic retrograde cholangiopancreatography. The serum level of IgG was elevated to 3450mg/dl. Besides, on the 10th hospital day, petechia developed and the platelet level decreased to 1.5 x 10(4)/microl. The platelet-associated IgG, antiplatelet antibody and antinuclear antibody in serum were positive. The levels of serum complements were low. From all these findings the patient was diagnosed as autoimmune pancreatitis complicated with immune thrombocytopenia. The treatment with prednisolone was started, which was effective on each disease. The medication was suspended a year ago, and so far there is no data suggesting the recurrence of autoimmune pancreatitis or immune thrombocytopenia.     

Asymptomatic primary mucinous cystadenocarcinoma of the appendix with a large abdominal mass: Report of a case

A case of cystadenocarcinoma of the appendix with a large cystic lesion is reported. A 49-year-old man undergoing a routine ultrasonic scan was incidentally found to have an abdominal mass measuring some 30 cm in size. The clinical presentation was asymptomatic, and the patient underwent a laparotomy without ascertaining a diagnosis preoperatively. The lesion, which derived from the appendix, was removed and was found to be cystic and contained huge amounts of mucin. The histological findings revealed a well-differentiated cystadenocarcinoma of the appendix, and immunohistochemical staining of the epithelium and mucinous implants in the mass demonstrated a positive reaction for carcinogenic antigens, including carcinoembryonic antigen and carbohydrate antigen.     

The role of gallium 67 imaging in non-Hodgkin's lymphoma of the gastrointestinal tract

To evaluate the clinical usefulness of gallium 67 imaging in the detection of gastrointestinal (GI) non-Hodgkin's lymphoma (NHL) and in the assessment of the therapeutic effects, images were reviewed in 24 cases (25 lesions: stomach, 20; ileum, 2; and terminal ileum and/or cecum, 3) and were compared using barium studies and, in 16 cases, computerized tomography (CT). In all, 23 (92.0%) of the 25 lesions were detected by⁶⁷Ga citrate imaging, the barium studies detected all 25, and CT detected 15 of 16 lesions (93.8%). The two lesions not identified by imaging and the one not found by CT were the smallest of all. In 2 (8.7%) of the 23 lesions positively identified by⁶⁷Ga-citrate imaging, both CT and imaging revealed the extent of the tumor more accurately than did the barium studies. In all but one of the patients, a close correlation existed between the imaging results and the therapeutic effects. These data suggest that⁶⁷Ga imaging is useful in conjunction with CT and barium studies for the detection of GI NHL and for the assessment of both the spatial extent of disease and the therapeutic effects, although a lack of⁶⁷Ga uptake after therapy does not always indicate a good therapeutic effect.     

Self-expanding endovascular graft: an experimental study in dogs

An arterial endovascular graft was constructed by wrapping an expandable nylon mesh around a framework of Gianturco self-expanding metallic stents. The devices were passed through a 12-French Teflon catheter and positioned in the normal abdominal aorta of five dogs, two of which also had a device placed in an external iliac artery. At follow-up (1-6 months), all grafts remained patent, even though slight luminal narrowing due to neointimal encasement was noted. Histologically, all grafts were covered by neointimal proliferation at the time of removal. The graft material expanded with the stents, resulting in a tight fit between the graft and the vessel wall. Side branches narrowed but remained open because of the size of the nylon mesh. No migration of the grafts equipped with a barbed lead stent was noted. Expandable nylon mesh can be used as an endovascular graft material when wrapped around a framework of self-expanding stents. The resulting device can be easily delivered via transcatheter techniques, and once placed in a vessel, the nylon acts as a support for neointimal encasement, which forms a new vascular lumen.