Biomechanical properties of heat-treated bone grafts.

INTRODUCTION: A possible critical complication associated with banking bone is human immunodeficiency virus (HIV) infection. Recently, since the report of HIV infection in bone allografts from an HIV-seronegative donor, a more reliable method of sterilization for preserved bone graft has become necessary. Heat treatment of banking bone is one of the simple sterilization methods. This method is especially safe and practical for the prevention of HIV infection. MATERIALS AND METHODS: We previously reported a biological study on heat-treated bone graft. In that study, we showed that revascularization and new bone formation of bone graft after heat treatment at 60 degrees C was nearly the same as that of non-heat-treated bone graft, while at 100 degrees C, revascularization and new bone formation showed a significant delay. This time, we examined the change of mechanical strength of heat-treated bone grafts after transplantation in an experiment. To eliminate the problem of antigenicity of grafted bone, we used autografts, not allografts. Two types of heat-treated autografts were employed: heat-treated at 60 degrees C for 30 min and heat-treated at 100 degrees C for 5 min; as a control, fresh autografts were replaced in the left femur of rabbits. A strength test was performed for both the transplanted bone and the untreated intact right femur with time after transplantation. The strength test consisted of a compression test and torsional test, and the strength was compared between transplanted bone and the untreated intact right femur. RESULTS: In the compression test, the grafts heat-treated at 60 degrees C showed a strength ratio before transplantation of 97.3%. The strength ratio decreased to 63.5% at 18 weeks after transplantation. Then the strength ratio increased and recovered to 94.5% at 48 weeks after transplantation. However, the grafts heat-treated at 100 degrees C showed unsatisfactory mechanical strength, at 48 weeks the strength ratio was 60.1%, which was significantly lower compared with controls. In the torsional test, the grafts heat-treated at 60 degrees C showed almost the same strength observed in the compression test. However, the grafts heat-treated at 100 degrees C showed unsatisfactory mechanical strength: at 48 weeks, the strength ratio was 57.3%. CONCLUSION: Therefore, heat treatment at 60 degrees C is a useful sterilization method, not only in biological but also mechanical terms.

Targeting superoxide dismutase to renal proximal tubule cells inhibits nephrotoxicity of cisplatin and increases the survival of cancer-bearing mice.

Because cis-diamminedichloroplatinum(II) (cisplatin) which generates reactive oxygen species induces renal dysfunction, administration of a large dose for killing cancer cells is highly limited. We recently synthesized a cationic superoxide dismutase (SOD) (hexamethylenediamine-conjugated SOD, AH-SOD) which rapidly accumulates in renal proximal tubule cells and inhibits oxidative injury of the kidney. Treatment of Ehrlich ascites tumor cells (EATC)-bearing mice with cisplatin sufficient for killing tumor cells increased their motality. The motality of cisplatin-treated EATC-bearing mice was markedly decreased by AH-SOD. These results suggest that targeting SOD to renal proximal tubule cells might permit the administration of high doses of cisplatin and related anticancer agents without causing renal injury.

Targeting superoxide dismutase to renal proximal tubule cells inhibits mitochondrial injury and renal dysfunction inuduced by cisplatin.

We recently reported the synthesis of a cationic superoxide dismutase (SOD) derivative (AH-SOD) that rapidly and selectively accumulates in and around proximal tubule cells and effectively dismutes superoxide radicals in situ. The present study revealed that administration of cis-diamminedichloroplatinum(II)-elicited oxidative stress in renal mitochondria, decreased the renal expression of Bcl-x, released cytochrome c from mitochondria to cytosol, and induced apoptosis and renal dysfunction by a mechanism that was inhibited by AH-SOD. These results suggest that targeting SOD to proximal tubule cells protects renal function and permits the administration of fairly high doses of nephrotoxic anticancer agents, such as cisplatin, without causing renal injury.

[Intracranial mesenchymal chondrosarcoma arising from the cerebellar tentorium: case report].

A 22-year-old woman presented with a 3-year history of progressive frontal headache. Computerized tomography (CT) and magnetic resonance imaging (MRI) revealed a tumor in the left trigone of the lateral ventricle and which enhanced homogeneously. The tumor was attached to the cerebellar tentorium and was compressing the brain stem. On the angiography, no tumor staining was seen. On November 26, 1996, total removal of the tumor was performed using the left subtemporal approach. The tumor was attached to the cerebellar tentorium. The pathological diagnosis was mesenchymal chondrosarcoma. After surgery, gamma-knife radiosurgery was carried out on the tentorium at the place where the tumor had been attached. There has been no recurrence for 6 months. Mesenchymal chondrosarcoma in the brain is very rare and therapy for this tumor is difficult. We report this rare tumor and the therapy is discussed.

[A case of posterior fossa hypertrophic pachymeningitis with hydrocephalus].

A 52-year-old woman was admitted to our hospital because of nausea, headache, ataxic gait, and memory disturbance. CT scans and MRI showed a markedly enhanced lesion in the dura mater of the posterior fossa, edema in the right cerebellar hemisphere, occlusion of the transverse sinus, and hydrocephalus, suggesting hypertrophic pachymeningitis. Chronic otitis media and mastoiditis were also noted. Subjective complaints diminished after steroid administration. The patient underwent right suboccipital craniectomy and biopsy. The dura mater was markedly thickened, and the cerebellar surface was edematous. Histological examination revealed the thickened dura mater to be infiltrated by chronic inflammatory cells of forming lymphatic follicles and accompanied by Langhans giant cells. Inflammatory cells were not found in the cerebellar parenchyma, but were present in the subarachnoid space. Acid-fast stain, PAS and Grocott stain were negative. The cause of the hypertrophic pachymeningitis in this patient, may have been related to the chronic otitis media, but the patient's clinical course suggested that it might represent so-called "idiopathic hypertrophic pachymeningitis".

Aneurysm of the posterior cerebral artery: report of eleven cases--surgical approaches and procedures.

Eleven cases of an aneurysm of the posterior cerebral artery are reported. All 11 aneurysms were saccular, and 3 were either giant or large. The aneurysms arose from the P1 segment in three patients, the P1-P2 junction in three patients, the P2 segment in three patients, and from the P3 segment in two patients. In all, 10 patients underwent surgery. All P1 and P1-P2 junction aneurysms were treated with the pterional approach. Three P2 and two P3 aneurysms were managed by the subtemporal approach. Two small aneurysms in the series were treated by coating the aneurysmal dome, two by clipping the afferent artery, and all other saccular type aneurysms were treated by clipping the aneurysmal neck. Seven patients had either an excellent or good outcome; two had poor results; and one patient died. The operative approaches and procedures are also discussed in relation to the anatomy of posterior cerebral artery aneurysms.

Alleviation of intestinal lesions by combined treatment with a 5-fluoro-2'-deoxyuridine (FUDR) derivative and alpha-difluoromethylornithine (DFMO)[correction of DMFO] in tumor-bearing mice.

alpha-Difluoromethylornithine (DFMO), an inhibitor of ornithine decarboxylase, reduced intestinal lesions in tumor-bearing mice caused by treatment with N3-(3-methylbenzoyl)-3',5'-diacetyl [corrected]-FUDR (FF-705), a derivative of 5-fluoro-2'-deoxyuridine (FUDR). FF-705 at 32 mg/kg (the effective dose) suppressed tumor growth to about 40% of the control level. At this dose, body weight gain was suppressed slightly when FF-705 was given alone, and this change was milder in the DFMO-supplemented group. Intestinal lesions were suppressed almost completely by concomitant treatment with DFMO. The gross lesion index in the combined treatment group was similar to that in the controls and significantly smaller than in the FF-705-alone group (0.3 and 1.9, respectively). The histological lesion index in the combined treatment group was also significantly smaller than in the FF-705-alone group (7.9 and 23.8, respectively). When FF-705 was given at 64 mg/kg, the intestinal mucosal lesions were more severe, but DFMO supplementation reduced them by approximately 50%. Moreover, maltase and diamine oxidase activities of intestinal epithelium remained higher with combined treatment than with FF-705 alone. With FF-705 at 256 mg/kg (a toxic dose), DFMO had little protective effect against intestinal damage.

[Clinical characteristics of the lung diseases due to Mycobacterium avium and Mycobacterium intracellulare classified by DNA probe test].

Clinical characteristics of the lung diseases due to M. avium and M. intracellulare classified by DNA probe test were investigated. Between M. avium and M. intracellulare, there was no significant differences in the samples' backgrounds and the clinical characteristics except for their prognoses. The prognosis of the lung diseases due to M. intracellulare was better than those due to M. avium, and M. avium was revealed to be highly susceptible to Cyclocerine than M. intracellulare. No remarkable difference was found in the susceptibility to other antituberculous drugs.

Carp (Cyprinus carpio) heart has a high sensitivity to the positive inotropic effect of strophanthidin despite negative force-frequency relationships.

1. The relationship between response of the heart to increased stimulation frequency and digitalis sensitivity was examined comparing the positive inotropic effect of strophanthidin and [3H]ouabain binding to sarcolemmal Na+, K+-activated adenosine triphosphatase (Na+, K+-ATPase) in carp heart, which showed a negative force-frequency relationship, and in guinea-pig heart, which has a positive relationship. 2. In ventricular muscle preparations isolated from carp heart, strophanthidin increased developed tension with a half-maximal effect observed at 0.31 microM, indicating a relatively high digitalis sensitivity of this preparation. 3. The positive inotropic effect was not altered by concentrations of propranolol sufficient to block beta-adrenergic receptors. 4. Specific binding of [3H]ouabain to homogenates obtained from ventricular muscle of carp heart showed a single class of binding sites with a Kd value of 26 nM. 5. Potency of strophanthidin to produce the positive inotropic effect and affinity of the binding sites for [3H]ouabain were both higher in carp heart compared to those in guinea-pig heart. 6. These results demonstrate a clear dissociation between the force-frequency relationship and the sensitivity of heart muscle to the positive inotropic effect of cardiotonic steroids. 7. The latter is primarily determined by affinity of sarcolemmal Na+, K+-ATPase for the cardiotonic steroids.

[Effect of calcium antagonist (diltiazem) on symptomatic cerebral vasospasm--with special reference to CT classification].

CT is important for detecting subarachnoid clots and intracerebral or intraventricular hemorrhage. The presence of subarachnoid clots surrounding the cerebral arteries may be one of the causes of cerebral vasospasm. It is agreed that there is a correspondence between the site of subarachnoid clots and the location of cerebral vasospasm. The authors have already reported that the appearance and severity of symptomatic cerebral vasospasm were not affected by calcium antagonists (Diltiazem), but the prognosis improved significantly for 105 patients (especially Hunt-Hess grade II and III) at the 3-month follow-up examination. In this study, the above 105 patients, each with a ruptured supratentorial aneurysm, were classified preoperatively according to Fisher's CT grading system and the effect of Diltiazem was re-examined. Patients in Hunt-Hess grade V were excluded and the duration of treatment with Diltiazem was 2 weeks following the operation. 105 cases (Diltiazem) were compared as a control group with 100 cases who were operated on before the administration of Diltiazem. The frequency of occurrence of symptomatic cerebral vasospasm tended to decline in patients with a CT grade of 2 or 3, and the prognosis improved significantly for 105 patients including 32 cases with symptomatic cerebral vasospasm. The preliminary results here indicate that Diltiazem might be especially effective for patients of Hunt-Hess grade II and III with CT grades of 2 and 3.

Studies on the anti-inflammatory activity and ulcerogenic adverse effect of thiazole derivatives, especially 2-amino-thiazoleacetic acid derivatives.

A series of derivatives of 4-arylthiazole acetic acid and 2-aminothiazole were studied with respect of their antiinflammatory effect in rat carrageenin edema. Some active compounds were found, which suppressed the paw edema formation strongly, and two compounds were selected, 4-(4-chlorophenyl)-2-phenylaminothiazole acetic acid (Compd. 29) and 4-(4-chlorophenyl)-2-diethylaminothiazole acetic acid (Compd. 71) for further detailed studies. These compounds (Compd. 29 and Compd. 71) moderately inhibited the denaturation of albumin with heat-treatment. Hyperthermic lysis of erythrocytes were strongly inhibited with both Compds. 29 and 71 in the wide range of concentrations (5 X 10(-5) mol/l-5 X 10(-4) mol/l), while their related compound, Compd. 2 (fentiazac) and the reference drugs, ibuprofen, phenylbutazone and flufenamic acid, were either ineffective or stimulatory at the higher concentration. Compds. 29 and 71 inhibited strongly both trypsin and chymotrypsin activities, which differed from the above reference drugs qualitatively and quantitatively. The adverse effect on the gastrointestinal membrane was less with Compd. 29 and Compd. 71 compared with fentiazac and ibuprofen. Compd. 29 especially gave the preferable results with almost no gastric damage at the higher dosage together with its good anti-edematous activity. The characteristics of Compds. 29 and 71 are discussed in terms of the correlation between anti-inflammatory effect and ulcerogenic effect and also of the clinical application.

[Absorption of the antibody formation to anticartilage-antiparathyroid antibodies administered into the rectum (author's transl)].

The absorption of and specific antibody formation to Artroglobina (:AG, beta and gamma-globulin fractions of anticartilage-antiparathyroid immune serum from the horse) administered into the rectum were studied in rats and guinea-pigs, an immunological tests in the "Phase I Study" were carried out using serum from volunteers. 1) When the radio-labelled AG (125I-AG) was administered into the rat rectum, the plasma level of 125I reached the maximum (3.1% of the total dosage) at 2 hour later and 0.3 per cent of the total dosage retained the reactivity with the anti-Fab antibody. 2) Gel diffusion and PCA tests gave positive reactions in the sera after the second administration of AG in a dose of 20 mg/kg, corresponding to 40 times the clinical dose, with a certain interval after the first treatment. From the results, it was confirmed that rectally-administered AG induces mainly IgG or IgE antibody formation, in the rat. 3) The administration of AG through the rectum did not induce the systemic anaphylaxic reaction in the guinea-pigs which had been administered AG into the rectum. The intravenous challenge, however, resulted in a positive anaphylaxic reaction in animals treated with AG rectally. This indicates the sensitization of the animal with AG by the rectal administration. 4) The specific antibody responses, immune complexes and complement values did not change in the sera of volunteers given AG which consisted of alternating cycles of twelve days of treatment with one suppository daily, and twelve days without treatment, in a clinical dose of 25 mg. Nevertheless, AG must be carefully prescribed as higher doses given to experimental animals induced adverse immunological effects.

[Binding activity of purified anticartilage-antiparathyroid antibodies to the cartilage in vitro (author's transl)].

We studied the binding activities especially the binding to the cartilage of the specific antibodies, which were purified from a new therapeutic agent of osteo-arthrosis, Artroglobina using several tissue materials. A purified specific antibodies pre-adsorbed with the pig liver and muscle homogenates lost the binding activity to the pig heart but retained the specific activity to the pig cartilage. The same results were obtained with the tissues from the rat and the hen. It also had the same activity on human cartilage, and the adsorption with the cartilage from either pig or human led the complete loss of the binding activity to the human cartilage. Evidence of the specific activity of these purified specific antibodies to the human cartilage in vitro suggests that further studies are warranted as a similar specific binding reaction of Artroglobina to the cartilage, in situ may occur of patients with osteo-arthritis and who are being treated clinically.

Antigen-binding activity and allergenicity of heterologous gamma-globulin absorbed from the rectum.

The molecular integrity of rectally absorbed antigens was studied in rats and mice. ABout 2% in the radioactivity of 125I-labelled horse gamma-globulin administered rectally reached the blood circulation. One fifth of this absorbed radioactivity (0.4%) reacted with anti-Fab antibody and about one eight (0.25%) of the original antigen-binding activity was maintained. The results indicated that a small but significant portion of the rectally administered proteins remained intact and retained the immunological function. Rectally-administered proteins induced IgE antibody responses in the rat and the mouse.