Enhanced effect of intra-arterial adriamycin administration in combination with degradable starch microspheres on an intra-arterial chemotherapy model of nude rats transplanted of human gastric cancer

Enhancement of the antitumor effects of adriamycin (ADR) by concomitant use of degradable starch microspheres (DSM) and pharmacokinetics of ADR in combination with DSM was investigated. An intra-arterial chemotherapy model of the nude rats transplanted of human gastric cancer xenografts (H-154) in the hind-limbs was used for this study. Drug was administered through a catheter inserted into the carotid artery with the tip in the common iliac artery. In the pharmacological study, increase of regional uptake of ADR and decrease of systemic distribution of ADR were recognized in some degree. DSM 30 mg/kg, which caused temporary arrest of blood flow in the tumor, had an only weak effect on tumor growth. ADR 3 mg/kg mixed with DSM 30 mg/kg was more effective than ADR 3 mg/kg solution. Furthermore, mixture of ADR 2 mg/kg and DSM 30 mg/kg had a greater effect on tumor growth than ADR 2 mg/kg following DSM 30 mg/kg. It seems that embolization by DSM, retention of ADR in regional tissues and cytotoxic effect of ADR have contributed to such a strong effect of ADR mixed with DSM.     

In vivo inhibition of superoxide production and protein kinase C activity in macrophages from vitamin E-treated rats

Rat peritoneal macrophages, which were induced by intraperitoneal injection of vitamin E for 6 successive days, contained 387.6 to 569.0 ng alpha-tocopherol/10(6) cells and produced 0.9 to 1.5 nmol O2-/min/10(6) cells following stimulation by phorbol myristate acetate (PMA). On the other hand, control macrophages contained 1.7 ng alpha-tocopherol/10(6) cells and produced 3.9 to 4.5 nmol O2-/min/10(6) cells. The particulate fraction of macrophages from vitamin E-treated rats contained 285.2 to 294.4 ng alpha-tocopherol/10(6) cells and showed scarcely any protein kinase C activity, whereas the specific activity of control rats showed 323 to 357 pmol/min/mg protein. From these results, we concluded that vitamin E seems to decrease O2- production from macrophages stimulated with PMA through inhibition of protein kinase C.     

Congenital pseudarthrosis of the tibia: analysis of the histology and the <Emphasis Type="Italic">NF1</Emphasis> gene

Background Congenital pseudarthrosis of the tibia (CPT) is frequently, but not always, associated with neurofibromatosis type 1 (NF1). Double inactivation of the NF1 gene has been reported to be the pathogenesis of CPT in NF1 cases. Methods We analyzed the loss of heterozygosity (LOH) of the NF1 gene in cases of CPT with NF1 to examine whether double inactivation was seen in the case. In addition to morphological analysis, immunoexpression of differentiation markers was examined. Results and discussion The tibia tapered with the zone phenomenon from mature to immature bone with osteoblastic rimming, resembling osteofibrous dysplasia. Osteosclerotic bowed bone with a small number of osteoclasts suggested dysfunction of bone remodeling. Fibrous tissue at the site of pseudarthrosis was associated with the periosteum and demonstrated myofibroblastic differentiation accompanied by massive cartilage formation, suggesting some misdirection during the differentiation of periosteum to myofibroblasts or chondrocytes. LOH of the NF1 gene locus was not seen in fibrous tissue. This result suggests that CPT is not accompanied by double inactivation in every NF1 case.     

Simultaneous corrections Bentall procedure, mitral valve replacement and sternoplasty for a patient with Marfan's syndrome

A successful case of simultaneous modified Bentall' procedure, MVR and sternoplasty was presented for a 42 years old man of Marfan's syndrome who had funnel chest, combined with mitral regurgitation, aortic regurgitation and annuloaortic ectasia. A few reports of one stage operation for the combination of funnel chest and heart disease in Marfan's syndrome has been published. A median sternotomy was made, with total cardiopulmonary bypass, heart was arrest and cor cooling hypothermia with crystalloid cardioplegic solution. Mitral valve was replaced with #31 B-S prosthetic valve. The ascending aorta proximal to the innominate artery and the aortic valve were replaced en-bloc with composite graft made of a vascular graft and aortic valve prostheses. Coronary artery orifices cut to the button-shaped, were sutured to the composite graft. Finally, sternoplasty was completed through modified Ravitch sterno-elevation. This is the first report in Japanese journals.     

Clinical study of primary carcinoma of the fallopian tube: experience with 14 cases

Between 1950 and 1986, 14 cases of primary carcinoma of the fallopian tube were treated and diagnosed at the Cancer Institute Hospital. These cases constituted 0.13% of the total number of gynecologic malignancies at the hospital during the period. The clinical/pathological findings and prognoses were described. Of the 14 cases, the average age was 56.0 years. The most frequent symptom was atypical genital bleeding, seen in 11 cases (79%). Massive watery discharge was seen in four cases (29%). In preoperative cytologic examination of vaginal smears, six cases (43%) were positive for cancer. All cases underwent operation as therapy. Postoperative irradiation, adjuvant chemotherapy, and/or second-or third- look operation was also used. Histopathologically, all materials were found to be adenocarcinoma. Four cases were well differentiated, seven were moderately differentiated, and three were poorly differentiated. Two patients with stage III and IV cancers died of the disease. Nine patients were still alive at the end of this study. The five-year survival rate was 57% (4/7). In stage I cancers, the five-year survival rate was 80% (4/5). The prognosis of stage I cancer patients was estimated as rather good.     

Prediction of spinal cord ischemia with a retrievable stent graft on endovascular treatment for a case of thoracic aortic aneurysm

Multiple aortic aneurysms in Behçet’s disease were repaired with transluminaly placed endovascular stent grafts. Before deploying the stent graft device for permanent implantation for the saccular aneurysm located in the descending thoracic arota, from which feeding arteries for the spinal cord possibly branched, a retrievable stent graft was inserted and evoked spinal cord potential (ESP) were monitored in order to predict spinal cord ischemia. The original retrievable stent graft, constructed of a self-expandable Z-shaped stainless steel stent covered with e-PTFE, can be easily withdrawn into a 18 Fr. sheath after deployment. Blood flow into intercostal arteries branching from that part of the descending aorta where the permanent stent graft is planned to be implanted, is intercepted by the retrievable stent graft. A change of ESP during the temporary implantation of the device indicates that spinal cord ischemia would be caused by permanent implantation of the stent graft. In this case, no change of ESP was observed and the patient showed no postoperative paraplegia.The retrievable stent graft was useful for prediction of spinal cord ischemia before endoluminal stent graft repair of the descending aortic aneurysm. However, the device is not flexible enough to fit a severely tortuous aorta, therefore we are obliged to select patients to some extent. Further improvement of the device is required to make prediction of spinal cord ischemia with the retrievable stent graft possible in all cases.     

Effects of Right Ventricular Failure on Renal Function During Pneumatic Left Ventricular Assist

Abstract: In an experimental dog model of acute biventricular failure, the effects of left ventricular (LV) assist on renal hemodynamics and function were evaluated. After the induction of severe cardiac failure by multiple ligation of the coronary arteries, LV assist with a 40 ml pneumatic pulsatile pump was initiated, and the aortic flow was maintained at control values. The right atrial pressure (RAP) rose to 21.3 mm Hg with the appearance of profound right ventricular (RV) failure. Renal arterial blood flow (RAF) decreased to about 60% of the control value after 2 h of LV assist. The urine volume decreased and renal function deteriorated progressively. RV assist decreased the RAP to 4.8 mm Hg, and the reduced RAF recovered. After 3 h of RV assist, the RAF returned to initial values and the urine volume increased, but renal function did not recover. Advanced biventricular failure with elevated RAP during LV assist reduced renal perfusion and impaired renal function and may be an indication for early RV assist     

Cardioprotective Effect of Succinate Against Ischemia/Reperfusion Injury

(Received for publication on Sept. 12, 1996; accepted on May 12, 1997)     

Bone marrow transplantation in miniature swine. III. Graft-versus-host disease and the effect of T cell depletion of marrow

Graft-versus-host disease (GVHD) has been evaluated in partially inbred miniature swine in order to study this complication of allogeneic bone marrow transplantation (BMT) in a major histocompatibility complex (MHC) genetically defined large animal model. Bone marrow from MHC homozygous ("parental") swine was injected into irradiated (900 rads total-body irradiation) MHC heterozygous ("F1") swine that shared one haplotype with the donor. All 18 animals successfully engrafted with donor bone marrow, and 17 of these developed skin rash of varying intensity depending on the extent of T cell depletion of infused marrow. Of 18 animals, 8 received undepleted bone marrow from exsanguinated donors and 2 also received additional peripheral blood lymphocytes (PBL) as a source of mature T cells. All 8 showed a moderate-to-severe rash, and the 2 pigs that received additional donor PBL developed the most severe rash. The cutaneous eruption seen in this model clinically, histologically, and immunologically resembled human GVHD. Two protocols of T cell depletion of donor bone marrow by antiporcine T cell monoclonal antibodies plus complement were tested for their effect on development of GVHD. The combination of two monoclonal antibodies, 74-12-4 (PT4) and 76-2-11 (PT8), had a marginal effect on the subsequent development of cutaneous manifestations of GVHD. However, treatment of the donor marrow by a combination of three monoclonal antibodies--PT4, PT8, and MSA4 (PT11)--effectively decreased the severity of the GVHD skin rash. These results indicate that (1) the GVHD associated with allogeneic bone marrow transplantation in swine is dependent on T cells in the marrow; (2) effective T cell depletion of donor marrow by monoclonal antibodies and complement does not prevent engraftment; and (3) this swine GVHD model, which allows study with F1 and homozygous parental combinations in an MHC genetically defined large animal, is particularly useful for the understanding of GVHD pathogenesis, prevention, and treatment.     

Similarities between the relaxations induced by vasoactive intestinal peptide and by stimulation of the non-adrenergic non-cholinergic neurons in the rat stomach

Summary The characteristics of the non-adrenergic, noncholinergic inhibitory response of the rat stomach fundus to transmural nerve stimulation were compared with the relaxation induced by vasoactive intestinal polypeptide (VIP). Treatment with -chymotrypsin (5 U/ml) or VIP antiserum (1:200) significantly reduced the relaxation induced by transmural nerve stimulation at 30 Hz, indicating that the possible transmitter in the non-adrenergic, non-cholinergic nerves is a peptide and may be VIP or a closely related peptide. VIP was able to relax, fully and dose-dependently, the stomach fundus that had previously been constricted by treatment with 10^–6 M serotonin, and the IC₅₀ value for VIP was 2.4 × 10^–9 M. VIP elevated levels of cyclic AMP in a dose-dependent manner and the EC₅₀ value was 2.8 × 10^–9 M in the presence of 10^–6 M atropine and 10^–6 M guanethidine. The stomach fundus was relaxed by transmural nerve stimulation (30 Hz, 50 mA) and transmural nerve stimulation also caused production of cyclic AMP in the rat stomach in the presence of atropine and guanethidine. The basal level of cyclic AMP in the stomach was 8.7 ± 0.26 pmole/mg protein. When transmural nerve stimulation was applied for 5 min, the contraction of the stomach, induced by 10^–6 M serotonin, was inhibited by 54% in the presence of atropine and guanethidine and the level of cyclic AMP was increased to 13.0 ± 0.73 pmol/mg protein. Apamin inhibited the transmural nerve stimulation-induced relaxation and shifted the dose-response curve for VIP to the right. These results suggest that one of the putative neurotransmitter from non-adrenergic, non-cholinergic nerves in the rat stomach is VIP and that VIP-induced relaxation may be mediated by the production of cyclic AMP and by the opening of apamin-sensitive K⁺-channels.Send offprint requests to K. Kamata at the above address