Effects of phenytoin on cell-mediated immunity

Phenytoin is a highly effective anticonvulsant agent that is widely administrated to prevent some kinds of patients with brain tumor. But it has been said that phenytoin may have some immunosuppresive potential for hosts. In this study, we evaluated the effects of phenytoin upon cellular immunity such as NK, CTL and LAK activity in murine models. Fresh splenocytes were taken out from mice (CBA/J, C 3 H/HeN, C 57 BL/6) into which phenytoin had been injected intraperitoneally at a daily dose of 1,000 micrograms for 28 days. The serum concentration of phenytoin in the experimental models was 10-20 micrograms/ml. The cytotoxic activities were estimated by a 4-hr 51Cr release assay. The mitogen-stimulated lymphocyte function was evaluated by 3H-thymidine incorporation into DNA. The NK activity was estimated by cytotoxicity of splenocytes of CBA/J mice against NK-sensitive YAC-1 cells. The cytotoxic T-lymphocyte (CTL) activity was estimated by cytotoxicity of splenocytes of C 57 BL/6 mice which were stimulated in vitro for 5 days by splenocytes of C 3H/HeN treated with mitomycin C, against RSV-M glioma cells. Lymphokine-activated killer (LAK) activity was estimated by cytotoxicity of LAK cells, which were induced from splenocytes of C 3 H/HeN mice by human recombinant interleukin-2 (rIL-2), against syngeneic RSV glioma and allogeneic 203 glioma cells. 3H-thymidine incorporation of splenocytes of C 57 BL/6 mice was reduced significantly (p less than 0.01) in phenytoin-treated mice. The cytotoxicity of splenocytes of non-treated CBA/J mice against YAC-1 cells was 75%, but that of phenytoin-treated CBL/J mice was a few %.(ABSTRACT TRUNCATED AT 250 WORDS)     

Assessing Health Disparities in Rural Hawaii Using the Hoshin Facilitation Method

CONTEXT: Health disparities between rural and urban communities are well documented. There are many suggested causes and many proposed solutions but no one-size-fits-all answer. The most successful community interventions have been introduced by communities themselves. However, before communities invest in such interventions, each group must identify and prioritize their needs. PURPOSE: This article describes the Hoshin facilitation method as a practical option assisting communities in assessing their needs and gaining consensus for future steps. METHODS: Thirty-four meetings were held in 11 rural communities in Hawaii using the Hoshin process to identify factors that impact rural health. Themes were identified by constant comparative analysis and thematic frequency described. Commonality of responses between communities was examined. Informal feedback was collected from meeting participants. FINDINGS: There was a great deal of commonality between community responses, with economic factors, drug use, lack of community leadership, lack of health care services and access to services, lack of healthy activities for youth, and poor public education being the most common issues noted. Group involvement in the meetings was high, and the facilitation method received positive feedback from participants. CONCLUSIONS: The Hoshin facilitation method is a very useful tool to help communities rapidly identify and prioritize areas for programmatic attention.     

A case of rheumatoid arthritis complicated with idiopathic thrombocytopenic purpura and Hashimoto's disease

A 37 year old nurse with the rare combination of idiopathic thrombocytopenic purpura (ITP), Hashimoto's thyroiditis and rheumatoid arthritis (RA) was reported. In 1983, six years before her final diagnosis was made, she presented with purpura over her extremities and swelling of the cervical lymph nodes. Laboratory findings showed the following: platelet count 15 x 10(3)/microliters, the number of megakaryocyte without platelet production in bone marrow was increased, platelet life span (T1/2) 11 min. A diagnosis of ITP was made. In 1984 goiter was noticed. Laboratory data were as follows: T3 502ng/ml, T4 27.0 micrograms/dl, thyroid test x 1,600, microsome test x 409,600. She was diagnosed as having ITP and Hashimotoxicosis. She had been uneventful except temporary hyperthyroidism until 1989 when she developed morning stiffness, polyarthralgia, swelling of PIP joints, contracture of elbow joints and hallux valgus. Laboratory investigation were reported as follows. ESR 111mm/h, platelet count 31 x 10(3)/microliters, platelet associated IgG 800ng/10(7) pl, antinuclear antibody x 2,560, rheumatoid factor 1+, microsome test x 1,600, anti-DNA antibody 3U/ml. Anti-Sm antibody and anti-RNP antibody were not detected. The LE cell test was negative. Schirmer test and sialography were interpreted as normal. These findings confirmed the diagnosis of RA in addition to ITP and Hashimoto's thyroiditis. The combination of RA, ITP and Hashimoto's thyroiditis is extremely rare although these three disorders are classified as autoimmune disease.     

Type-II collagen gene expression is transiently upregulated in experimentally induced degeneration of rabbit intervertebral disc

To clarify phenotypic alterations of intervertebral disc cells during the repair process, we cloned partial type-II collagen cDNA from rabbits and analyzed the level of expression of type-II collagen mRNA in disc degeneration. An animal model was created by surgical denucleation of rabbit intervertebral discs through, an extraperitoneal approach. Eight animals each from an experimental and a control group were killed at 2, 4, 8, or 16 weeks postoperatively, and the disc samples were used for this study. Round chondrorcyte-like cells that filled the herniated space showed intense signal of type-II collagen mRNA and significant pericellular immunostaining of type-II collagen but no clear staining of type-I collagen. Northern. blot analysis revealed that the expression of type-II collagen mRNA of the repair disc cells was transiently increased at 4 weeks postoperatively. The cells were able to change their morphology in response to mechanical stimulation by surgical denucleation and to induce a significant increase in the gene expression of type-II collagen at an early phase of disc degeneration. The present results indicate the transient enhancement of repair activity in the degenerative process of injured fibrocartilage.     

A case of pulmonary aspergillosis presenting pulmonary bulla and eosinophilic pneumonia

A rare case of a 25-year-old man with pulmonary aspergillosis is reported. Pulmonary bulla and eosinophilic pneumonia in the right upper lobe were diagnosed by chest roentgenogram and transbronchial lung biopsy. Because the patient developed infective bullae during steroid therapy, we performed transcutaneous thoracic drainage and right upper lobectomy. The resected lung tissue contained numerous hyphae of Aspergillus. Around the hyphae of Aspergillus, granulomatous reaction and eosinophilic infiltration were observed. Antibodies against Aspergillus were detected in the serum of the patient. The number of peripheral blood eosinophils decreased after right upper lobectomy. These findings suggest that pulmonary bullae and eosinophilic pneumonia may be a rare manifestation of pulmonary aspergillosis.     

Distribution of radiolabeled 1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3-(2-chloroethyl)-3-nitros ourea hydrochloride in rat brain tumor: intraarterial versus intravenous administration

To assess the rationale of intraarterial (i.a.) 1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3-(2-chloroethyl)-3-nitrosourea chemotherapy, distribution of 14C-labeled 1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3-(2-chloroethyl)- 3-nitrosourea in rat glioma was studied after i.a. or i.v. infusion. Immediately after infusion, the tumor located in the hemisphere of intracarotid infusion received 4.6-fold higher radioactivity than the tumor located contralaterally to intracarotid infusion and 2.8-fold higher radioactivity than i.v. infusion. The difference was kept up to 30 min after i.a. infusion. Autoradiographic observation indicated rather uniform distribution of the tracer in the central portion of i.a. infusion. However, in the periphery of i.a. infusion, distribution of the tracer was nonhomogenous. The results indicate that i.a. 1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3-(2-chloroethyl)-3-nitrosourea chemotherapy is useful when the tumor has high blood flow and is located in the center of an infused area.     

Radiotherapy for malignant fistula to other tract

Radiotherapy was applied to 14 esophageal carcinomas with respiratory tract fistulas using various treatment regimens. Closure of the fistulas was observed in four cases after irradiation at a daily dose of 1.5 Gy. The period of closure was transient in two cases but long-term in the other two. One long-term closure case underwent low-dose rate telecobalt therapy (LDRT)(1 Gy per hour, 7 Gy per day; a total dose of 28 Gy) as a boost. His cancer has been well controlled and he is still alive without recurrence at 74 months after fistula formation.     

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.     

Response of postapoplectic hemichorea/ballism to GPi pallidotomy: progressive improvement resulting in complete relief.

We report on a 66-year-old woman in whom GPi pallidotomy produced progressive and eventually complete relief of hemichorea/ballism (HCB) after a subthalamic hemorrhage. Although choreoballistic movements were unchanged during and immediately after the surgery, the symptoms were gradually improved and consequently abolished by 5 days postoperatively. HCB has never recurred up to the present (9 months follow-up period). This note is the first report describing detailed postsurgical process in HCB relief after pallidotomy.