Effect of thermosensitive liposomal doxorubicin with hyperthermia on primary tumor and lung metastases in hamster osteosarcoma.

We evaluated the effect of intravenous thermosensitive liposomal doxorubicin (TL-DOX) together with local hyperthermia on primary tumors in highly metastatic hamster osteosarcoma. This combination resulted in higher DOX concentrations in plasma, primary tumors and lungs than standard DOX under the same conditions. Tumor growth and lung metastasis were also inhibited more by TL-DOX and hyperthermia than by hyperthermia alone, DOX with or without hyperthermia, and TL-DOX without hyperthermia. In addition, gains in hamster body weight were not suppressed. These results suggest that the combination of TL-DOX and hyperthermia can control primary tumors and suppress lung metastasis in hamsters.

A day care program and evaluation of animal-assisted therapy (AAT) for the elderly with senile dementia.

We conducted a survey to clarify the evaluation methods of animal-assisted therapy (AAT) for the elderly with senile dementia in an adult day care center. AAT was implemented for a total of six biweekly sessions. The AAT group consisted of seven subjects and the control group numbered 20 subjects. In a comparison between Mini-Mental State Exam (MMSE) scores at baseline and those measured three months later, the average MMSE score before AAT (baseline) was 11.43 (+/- 9.00), and three months later it was 12.29(+/- 9.69). In the AAT group, the average score on Nishimura's Activities of Daily Living (N-ADL) at baseline was 28.43(+/- 14.00), and after ATT it was 29.57(+/- 14.47). In the AAT group, the average baseline score on behavioral pathology of Alzheimer's disease (Behave-AD) was 11.14(+/- 4.85), and three months after AAT it was 7.29(+/- 7.11) (p < 0.05). In the control group, the average baseline score was 5.45(+/- 3.27) and three months later it was 5.63(+/- 3.59). The evaluation of salivary CgA, as a mental stress index, showed a decreasing tendency in the AAT group. Our findings demonstrate the usefulness of using several methods for evaluation of the changes in patients given AAT.

[Emergent surgical treatment of type A acute aortic dissection in an elderly patient].

An 86-year-old man with severe chest pain and shock was transferred to our hospital. Computed tomography revealed type A aortic dissection with cardiac tamponade. He needed intubation and closed chest massage preoperatively. At operation, intrapericardial space was filled with clotted blood and rupture of the ascending aorta was confirmed. He underwent a successful emergency graft replacement of the ascending aorta. Postoperative course was uneventful except for mild hemianopsia due to cerebral infarction. He had recovered to be able to walk and is doing well.

Immunosuppressive effects of the heat shock protein 90-binding antibiotic geldanamycin.

Ansamycin antibiotic, geldanamycin has a unique pharmacological effect to bind to heat shock protein 90 (hsp90) and deplete hsp90 substrates. We investigated the immunopharmacological effects of geldanamycin. Geldanamycin depleted cellular Raf-1 of rat splenic cells without affecting the steady state levels of hsp90 and downstream mitogen activated protein (MAP) kinases, ERK1 and ERK2. In parallel, it inhibited mitogen-induced nuclear factor-kappa B (NF-kappa B) activation in these cells. Geldanamycin also had a potent suppressive effect on recall antigen-induced T cell proliferation, with an IC50 value of 1 nM. In vivo, geldanamycin suppressed the progression of adjuvant-induced arthritis dose-dependently. These results suggest that geldanamycin exerts an immunosuppressive effect partly through destabilizing Raf-1, and raise a new strategy for the prevention of inflammatory diseases.

Neoadjuvant chemotherapy followed by concurrent chemotherapy and radiotherapy for locally advanced esophageal carcinoma with bulky upper abdominal lymphadenopathy. Case report.

A 60-year old male patient who had locally advanced esophageal carcinoma with bulky upper abdominal lymphadenopathy underwent neoadjuvant chemotherapy consisting of 5-fluorouracil (5-FU) and cisplatin (CDDP), followed by concurrent radiotherapy and chemotherapy using protracted low-dose continuous infusion of 5-FU and CDDP. The treatment brought about complete remission in the primary lesion and good partial remission in the upper abdominal lymphadenopathy. He subsequently underwent trans-hiatal esophagectomy after one cycle of adjuvant chemotherapy because local recurrence was suspected. Histopathologic study of the resected specimen demonstrated no malignant tissue in the primary lesion and the lymph nodes. The patient is still alive and disease-free at 26+ months. This result suggests that neoadjuvant chemotherapy followed by concomitant chemotherapy and radiotherapy for patients who have locally advanced squamous cell carcinoma of the esophagus with intensive abdominal lymphadenopathy may offer some chance for sterilization of local and regional metastases and longer survival.

Suppression of arthritis by the inhibitors of dipeptidyl peptidase IV.

Dipeptidyl peptidase IV (DP IV, CD26) is a serine exoprotease which selectively cleaves the penultimate proline residue of polypeptides. This enzyme is also expressed as a surface marker on activated T cells. In order to assess the relevance of DP IV in immunological disorders, we evaluated the in vivo effects of specific DP IV inhibitors using two arthritis models, one which was induced by collagen one by alkyldiamine. These animal models share several pathological features associated with rheumatoid arthritis. The transition state substrate analog of DP IV, (S)-Alanylpyrrolidine-boronic Acid (Ala-boroPro), suppressed hind paw swelling, which was associated with collagen-induced and alkyldiamine-induced arthritis. A competitive inhibitor of DP IV, Lys(Z(NO2))-thiazolidide and an irreversible inhibitor, Ala-Pro-nitrobenzoylhydroxylamine also suppressed alkyldiamine-induced arthritis dose-dependently. We also analyzed the pharmacological effects of Lys(Z(NO2))-thiazolidide on several immune responses in vitro, in order to determine its mode of action. This inhibitor suppressed mitogen-induced and antigen-induced proliferation of T cells. However, studies using splenic cells from DP IV deficient rats showed that the inhibition of lymphocyte proliferation was not exerted through the inhibition of DP IV.

Copper deficiency in an infant on prolonged total parenteral nutrition.

An infant with the megacystis microcolon intestinal hypoperistalsis syndrome, required total parenteral nutrition due to ineffective gastrointestinal function, and developed copper deficiency after a prolonged course in total parenteral nutrition in conjunction with a chronic draining jejunostomy. She responded promptly to copper supplementation.

Induction of acute myoclonic encephalopathy in hamsters by subacute sclerosing panencephalitis virus.

Myoclonus is a characteristic neurological sign of subacute sclerosing panencephalitis (SSPE). Attempts were made to induce myoclonus in a large proportion of hamsters with a cell-associated strain of SSPE virus (the Biken strain) and thereby to establish an experimental model for study of the mechanism of development of this condition. When injected intracerebrally, Biken virus induced myoclonus within two to 14 days in 84% of the three- to nine-week-old hamsters tested. Electroencephalographic traces showed a periodic and synchronous discharge consisting of high-voltage slow waves and spikes that appeared coincidentally with myoclonus. Neurons in the cortex and thalamus of the affected animals had severely degenerated cytoplasm. Inflammatory changes, such as perivascular cuffing or infiltration of mononuclear cells, were not detected. Staining with immunoperoxidase revealed measles viral antigens in the cytoplasm and dendrites of the affected neurons. SSPE virus with the same properties as the parent virus was recovered from brain cells of sick animals by cocultivation with Vero cells.

[High-dose combination chemotherapy with autologous bone marrow transplantation in breast carcinoma].

Twelve patients with breast carcinoma were treated with high-dose combination chemotherapy supported by autologous bone marrow transplantation (ABMT). Seven of them had advanced metastatic disease and received 12 cours of A treatment, response rate (CR +PR) was 71.5% (CR: 1, PR: 4, NC: 2 and PD: 0) and it should be noted that all 4 patients who had received adriamycin 150 mg+5-fluorouracil 1,500 mg divided in two consecutive days or equivalent high-dose of other chemotherapeutic regimen responded (CR: 1 and PR: 3). To the therapy Five other patients received ABMT-supported adjuvant chemotherapy because of high risk of recurrence. One of them died of unrelated cause and other 4 are free of disease at 11, 14, 17 and 17 months following this treatment. A major toxicity was of myelosuppression and nadirs of neutrophils were 100-1,800 on days 9-19 (median: 400 on day 12), neutrophils recovered rather rapidly to levels of greater than or equal to 1,000, greater than or equal to 1,500 and greater than or equal to 2,000 by day 15, 16 and 17, respectively. High-dose combination chemotherapy with ABMT seemed quite effective in advanced breast carcinoma and a similar approach in adjuvant setting has also been suggested.