Rectal dose-sparing effect with bioabsorbable spacer placement in carbon ion radiotherapy for sacral chordoma: dosimetric comparison of a simulation study

It is difficult to treat patients with an inoperable sarcoma adjacent to the gastrointestinal (GI) tract using carbon ion radiotherapy (C-ion RT), owing to the possible development of serious GI toxicities. In such cases, spacer placement may be useful in physically separating the tumor and the GI tract. We aimed to evaluate the usefulness of spacer placement by conducting a simulation study of dosimetric comparison in a patient with sacral chordoma adjacent to the rectum treated with C-ion RT. The sacral chordoma was located in the third to fourth sacral spinal segments, in extensive contact with and compressing the rectum. Conventional C-ion RT was not indicated because the rectal dose would exceed the tolerance dose. Because we chose spacer placement surgery to physically separate the tumor and the rectum before C-ion RT, bioabsorbable spacer sheets were inserted by open surgery. After spacer placement, 67.2 Gy [relative biological effectiveness (RBE)] of C-ion RT was administered. The thickness of the spacer was stable at 13–14 mm during C-ion RT. Comparing the dose–volume histogram (DVH) parameters, D_max for the rectum was reduced from 67 Gy (RBE) in the no spacer plan (simulation plan) to 45 Gy (RBE) in the spacer placement plan (actual plan) when a prescribed dose was administered to the tumor. Spacer placement was advantageous for irradiating the tumor and the rectum, demonstrated using the DVH parameter analysis.     

Involvement of central histaminergic and cholinergic systems in the morphine-induced increase in blood-brain barrier permeability to sodium fluorescein in mice

Summary Morphine (5 mg/kg, s.c.) caused a submaximal increase in the brain level of sodium fluorescein administered i.v. Histamine H₁-antagonists, diphenhydramine and mepyramine, given either i.p. or i.c.v., had no significant influence on the effect of morphine. H₂-Antagonists, cimetidine and ranitidine, administered i.c.v., but not i.p., significantly inhibited the morphine effect. -Fluoromethylhistidine, a specific histidine decarboxylase inhibitor (given i.p. and i.e.v.) and antimuscarinic drugs, atropine and biperiden, but not methylatropine (given i.p.) also significantly reduced the morphine effect. Physostigmine (i.p.) significantly enhanced the effects of 0.5 and 1 mg/kg of morphine. Similar effects of histaminergic and cholinergic drugs were also observed on the buprenorphine- and DAGO-induced increase in blood-brain barrier (BBB) permeability to sodium fluorescein. None of the treatments with 6-hydroxydopamine, -methylayrosine, 5,7-dihydroxytryptamine or p-chlorophenylamine had any significant effect on the morphine-induced increase in BBB permeability. These findings suggest that the activation of brain H₂-receptors by neuronal histamine and muscarinic receptors by acetylcholine is involved in the increase in BBB permeability to sodium fluorescein caused by opioid receptor agonists. Send offprint requests to K. Saeki at the above address     

Interleukin 12 production by monocytes from patients with psoriasis and its inhibition by ciclosporin A

BACKGROUND: Psoriasis is a T-helper (Th)1 cytokine-mediated chronic skin disease and interleukin (IL)-12 has been shown to play a major role in the development of Th1 responses. OBJECTIVES: To elucidate the role of IL-12 in the pathogenesis of psoriasis and to study the effect of ciclosporin A (CsA) on Th1 deviation of this disease. PATIENTS/METHODS: We investigated IL-12 production by stimulated monocytes from patients with psoriasis who were treated with or without CsA. Monocytes were stimulated with interferon-gamma plus lipopolysaccharide (LPS) or Staphylococcus aureus Cowan strain I (SAC). The amount of IL-12 p70 produced by stimulated monocytes was evaluated by enzyme-linked immunosorbent assay. RESULTS: Compared with those from normal controls, LPS- but not SAC-stimulated monocytes from patients with psoriasis produced significantly higher amounts of IL-12. Interestingly, LPS-stimulated monocytes from patients with psoriasis treated with CsA produced significantly decreased amounts of IL-12 compared with those patients not treated with CsA. CONCLUSIONS: Our results suggest that IL-12 production by monocytes may have a critical role in the pathogenesis of psoriasis, and that the therapeutic effect of CsA on psoriasis may be achieved by correcting the deviation of the Th1/Th2 balance.     

Hirschsprung’s disease patients diagnosed at over 15 years of age: an analysis of a Japanese nationwide survey

Purpose  

Hirschsprung’s disease (HD) is usually diagnosed in patients who are under 1 year of age, however, there are still several reports of adult HD cases. We herein analyzed the data of HD patients collected over 30 years according to a nationwide survey in Japan.     

Diverse Effects of Cytochalasin B on Priming and Triggering the Respiratory Burst Activity in Human Neutrophils and Monocytes

Cytochalasin B, despite its potent enhancing effect on superoxide (O2-) release triggered by N-formyl-methionyl-leucyl-phenylalanine (FMLP) and many other agonists, significantly inhibited O2- release triggered by interleukin 8 (IL-8) and platelet-activating factor in human neutrophils. Cytochalasin B also enhanced changes in membrane potential stimulated by FMLP but inhibited those stimulated by IL-8. Using IL-8 as a triggering agonist, we found that the priming effect of tumor necrosis factor (TNF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) on O2- release was slightly but significantly potentiated by cytochalasin B. O2- release triggered by TNF and GM-CSF was completely abolished by cytochalasin B. In contrast to these diverse effects of cytochalasin B on O2- release, changes in cytoplasmic pH stimulated by FMLP, IL-8, TNF, and GM-CSF were not or were only minimally affected by cytochalasin B. Unlike human neutrophils, human monocytes stimulated by FMLP showed inhibition of O2- release and changes in membrane potential in response to cytochalasin B, and the priming effect of TNF and GM-CSF on O2- release in human monocytes was completely abolished by cytochalasin B. These findings indicate the diverse effects of cytochalasin B on phagocytes and suggest distinct regulatory mechanisms according to the functions, agonists, and cell types.     

Enhancement of fibrinolytics with a laser-induced liquid jet.

BACKGROUND AND OBJECTIVE: There are several problems inherent in the treatment of cerebral embolisms, such as the narrow therapeutic time window and the severe side effects of fibrinolytic drugs. There is thus need of a new method of removing a cerebral thrombus more rapidly using smaller amounts of fibrinolytics. STUDY DESIGN/MATERIALS AND METHODS: The liquid-jet generator was made by insertion of an optical fiber (diameter: 0.6 mm) into a balloon catheter (6 Fr). A pulsed holmium (Ho) YAG laser (pulse duration time = 350 micros) was used as a laser source. The maximum penetration depth of a liquid jet generated with this device into a gelatin artificial thrombus was measured at various stand-off distances (L; distance between the optical fiber end and the catheter exit). Based on the result, a stand-off distance of 13 mm was chosen to investigate the enhancement of urokinase (UK) efficacy by only a single operation of the liquid-jet device in artificial thrombi made of human blood. RESULTS: Maximum penetration depth increased in proportion to L and reached a maximum value (9 mm) when L was around 13 mm. Fibrinolysis rates (%) after incubation with a small amount of UK for 10 and 30 minutes were predominantly raised by a single use of the laser-induced liquid jet (5.4 +/- 2.4 vs. 22.6 +/- 6.1 and 7.3 +/- 3.8 vs. 38.3 +/- 5.6, respectively (mean +/- SD, P < 0.001)). CONCLUSIONS: A laser-induced liquid jet effectively promoted fibrinolysis in vitro with use of only a small amount of fibrinolytics.     

Increased experimental pulmonary metastasis in pregnant mice

The effect of pregnancy on experimental pulmonary metastasis was studied. Compared to the incidence of pulmonary metastasis induced by G6 cells in non-pregnant mice, the incidence of such metastasis was found to be greatly enhanced when the cells were injected i.v. in the latter half of pregnancy. The maximum enhancement was seen on the 15th day of pregnancy. The incidence of pulmonary metastasis returned to the level observed in non-pregnant mice when the cells were injected 4 days after parturition. Pregnancy also significantly increased the incidence of pulmonary metastasis of 2 other cell lines (3LL and Colon 26). Injection of G6 cells after hysterectomy performed on the 15th day of pregnancy resulted in decreased lung colonization, similar to that seen after parturition. Quantificative analysis of the arrest of G6 cells labeled with [¹²⁵1]-5-iodo-2′-deoxyuridine in the lungs showed that the tumor-cell clearance from the lungs during the 24–72 hr after tumor-cell injection was much slower in pregnant than in non-pregnant mice. The continuous administration of β-estradiol and/or progesterone, which maintained serum levels of the hormones equivalent to those prevailing on the 15th day of pregnancy, did not affect the lung colonization of G6 cells. Tumor-cell-platelet aggregation was more extensive with platelets obtained from mice at the 15th day of pregnancy than with those from non-pregnant mice. When platelets isolated from pregnant mice were injected into normal mice 5 min before G6 injection, lung metastasis was also enhanced. These findings suggest that a pregnant host is handicapped with regard to pulmonary metastasis, this being partly due to increased platelet-aggregating activity in response to tumor cells. © 1995 Wiley-Liss Inc.