Spontaneous transection of a Raimondi peritoneal catheter--a case report with scanning electron microscopic study of the transected tube

Spontaneous transection of Raimondi peritoneal catheter is reported. A 6-month-old boy with communicating hydrocephalus had ventriculoperitoneal shunt surgery using Raimondi peritoneal catheter. Six months later, Raimondi catheter was found to be spontaneously transected in a peritoneal cavity. At the age of 5 year-old, the originally installed Raimondi catheter was again transected on the portion of chest wall. Scanning electron microscopic examination of the broken end of spring wire suggested that transection was caused by repetitive exertion of external forces. Mechanisms of transection of this catheter was discussed with review of the literature.     

Sequential PET studies in neuro-behcet's syndrome

Summary A case of neuro-Behcet's syndrome is presented with sequential positron emission tomography (PET) studies. Regional cerebral blood flow (rCBF) and oxygen consumption (rCMRO₂) were decreased in the brain lesion; however, on follow-up studies 3 months after steroid therapy rCBF and rCMRO₂ had increased in the lesion, which demonstrated the reversibility of this disease. Such monitored improvement may accurately reflect the early stage of the disease and its response to steroid therapy.     

Demonstration of cerebral radiation injury with metabolic positron emission tomography images.

A 2-year-old girl with medulloblastoma who had postoperative radiotherapy and intrathecal administration of methotrexate is reported. Five months after radiation and chemotherapy, she developed involuntary movement. Positron emission tomography (PET) demonstrated that the metabolic rate of glucose was depressed markedly in the temporal and occipital lobes, indicative of metabolic depression induced by radiation. Prompt initiation of steroid therapy ameliorated the patient's neurological symptoms. Follow-up PET revealed an increase in 18F-fluorodeoxyglucose uptake in the entire brain, including temporal and occipital lesions. No areas with high accumulation of (11C-methyl)-L-methionine were detectable. We concluded that PET may be useful in establishing an early diagnosis of radiation injury of the brain and in monitoring metabolic changes following radiation in brain tumor patients.     

Influence of O6-methylguanine-DNA methyltransferase activity on chloroethylnitrosourea chemotherapy in brain tumors

Chloroethylnitrosoureas (CENUs) alkylate DNA at specific sites and inhibit DNA replication in tumor cells. O⁶-Alkylguanine moieties resulting from alkylation of guanine bases are thought to be one of most lethal adducts in living cells. Effectiveness of CENUs is known to relate well with an enzymic activity of the DNA repair enzyme O⁶-methylguanine-DNA methyltransferase (MGMT), which recognizes and removes O⁶-alkylguanine. To improve therapeutic results of CENUs, we have measured MGMT activity of human brain tumors and studied the relationship between MGMT activity and clinical responsiveness to 1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3-(2-chloroethyl)-3-nitrosourea hydrochloride (ACNU). Thirty-seven patients with brain tumors were entered into the study. The neoplasms included gliomas, non-glial tumors, and brain metastases. The MGMT activity of gliomas was significantly lower than that of non-glial tumors and brain metastases. No significant difference in the enzyme activity was noted between low- and high-grade gliomas. Out of the 22 gliomas 5 tumors indicated a value below 60 fmol/mg, suggestive of a methyl excision repair minus (Mer^?) tumor. Two out of 3 evaluable patients with a Mer^? tumor responded well to post-operative ACNU adjuvant chemotherapy. Our results suggest that brain tumors include a certain percentage of Mer^? phenotype tumors, and that CENUs such as ACNU should be applied selectively on tumors with a low MGMT activity in order to increase the therapeutic effectiveness. © 1993 Wiley-Liss, Inc.     

Primary central nervous system involvement of the so called ‘peripheral T-cell lymphoma’. Report of a case and review of the literature

Epidural neuroblastoma xenografts in nude rats causing paraparesis were treated with intravenous injection of an anti-GD₂ monoclonal antibody 3F8. Metastatic or primary epidural tumors in humans cause rapid neurologic compromise. Treatment is often unsatisfactory. An animal model was established to study antibody targeted therapy of epidural tumor. Human neuroblastoma was xenotransplanted into the thoracic epidural space of nude rats. When paraparesis developed, animals were treated intravenously with an anti-GD2 monoclonal antibody, 3F8, either alone or radiolabeled with¹³¹Iodine. Improvement in neurologic function occurred in 2 of 20 (10%) animals receiving no treatment or control antibody, 14 of 17 (82%) animals receiving 3F8 alone and all 9 animals receiving¹³¹I-3F8 (p<0.0001 for 3F8 or¹³¹I-3F8 vs. control). Six animals treated with 3F8 alone recovered normal neurologic function and remained well until sacrifice 10 days later. Four animals treated with 3F8 alone had no tumor evident on pathologic examination. The percent injected dose of¹³¹I-3F8/g tumor in 5 samples ranged from 0.73% to 3.8%. These observations demonstrate that neoplastic epidural compression of the spinal cord in the rat can be treated successfully with intravenous unmodified monoclonal antibody and that signs of neurologic dysfunction can be reversed. The potential of this approach in treating patients with epidural tumors and other neoplasms, especially those that are not sensitive to chemotherapy or radiotherapy, deserves to be explored.     

Linkage between O6-methylguanine-DNA methyltransferase (O6-MT) activity and cellular resistance to antitumour nitrosoureas in cultured rat brain tumour cell strains

Summary We have examined O⁶-methylguanine-DNA methyltransferase (O⁶-MT) activity of rat brain tumour cell strains with reference to cellular resistance to antitumour nitrosoureas, 1-(4-amino-2-methyl-5-pyrimidinyl) methyl-3-(2-chloroethyl)-3-nitrosourea hydrochloride (nimustine, ACNU) and methyl-6-[3-(2-chloroethyl)-3-nitrosoureido]-6-deoxy--D-glucopyranoside (ramustine, MCNU). The values of O⁶-MT activity were 52 and 160 fmol/mg protein extract in 9 L and C 6 rat brain tumour cells, respectively; while HeLa S 3 cells, as a methyl excision repair positive (Mer⁺) cell strain, revealed a rather high value of 488 fmol/mg. 9 L cells indicative of a low O⁶-MT activity showed 13 M for ACNU and 18 M for MCNU at a 10% survival dose (SD₁₀), determined by a clonogenic cell assay as an index of cellular resistance. In contrast to this, C 6 cells revealed a SD₁₀ value of 67 M and 36 M for ACNU and MCNU, respectively, indicating higher resistance than 9 L cells. HeLa S 3 cells showed the highest SD₁₀ value as follows: 84 M for ACNU and 73 M for MCNU. The relationship between the O⁶-MT activity and the cellular resistance was almost linear, with relatively resistant cell lines exhibiting the higher levels of the O⁶-MT activity. This correlation between the O⁶-MT activity and the cellular resistance to nitrosoureas as ACNU and MCNU was not observed among other antitumour drugs, which included bleomycin (BUM), neocarzinostatin (NCS),cis-diamminedichloroplatinum (II) (CDDP), and etoposide (VP-16) in clinical use for brain tumour chemotherapy. This indicates that O⁶-MT activity can be an indicator of cellular resistance to antitumour nitrosoureas in the chemotherapy of brain tumours.     

Malignant gliomas treated with split course radiotherapy plus chemotherapy

Twenty-five adult patients with supratentorial malignant gliomas (malignant astrocytoma and glioblastoma multiforme) verified histologically from 1979 to 1986 postoperatively received combined modalities of split course radiotherapy (sRT), nimustine hydrochloride (ACNU), and tegafur (FT). The initial course of radiation consisted of 30 Gy whole brain in 15 fractions five days a week. After a one-week interruption, local radiation with a limited field including a tumor and a margin was boosted to a total dose of about 50-60 Gy. The results were compared with historical control comprising malignant gliomas which received continuous course of radiotherapy (cRT) with or without other chemotherapy before 1979 and after 1986. The median survival time (MST) of malignant gliomas was 18 months for sRT plus chemotherapy, 12 months for cRT alone, and 13 months for cRT plus chemotherapy. No differences between the Kaplan-Meier survival curves were significant by the generalized Wilcoxon test. Tumor histology, Karnofsky performance status, and patient age related well with survival.     

Transient activation of Notch signaling in the injured adult brain

Brain injury induces various kinds of cellular responses that lead to tissue regeneration and repair. Recent studies have demonstrated that resident progenitors proliferate and then differentiate into mature neuronal cells. We show here that proliferating cells in the cryo-injured cerebral cortex transiently expressed Notch1 immunoreactivity in their cytoplasm. Since activated Notch signaling regulates cellular fate in the developing nervous system, similar regulation may exist in the injured adult brain. To monitor the Notch signaling pathway, we examined whether components of the signaling pathway were co-expressed in Notch1-positive cells. Presenilin-1, a membrane-spanning protease that is required for the release of the Notch intracellular domain, was detected in the Notch1-positive cells and Hes1, a target of the Notch intracellular domain, also co-localized with Notch1 three days after cryo-injury. These results suggest that transient activity of the Notch signaling pathway is involved in the regulation of proliferation and differentiation of progenitors in the injured brain.     

Multidisciplinary Team-Based Palliative Care for Heart Failure and Food Intake at the End of Life

Traditionally, patients with end-stage heart failure (HF) have rarely been involved in end-of-life care (EOLC) discussions in Japan. The purpose of this study was to examine the impact of HF-specific palliative care team (HF-PCT) activities on EOLC discussions with patients, HF therapy and care, and food intake at the end of life. We retrospectively analyzed 52 consecutive patients with HF (mean age, 70 ± 15 years; 42% female) who died at our hospital between May 2013 and July 2020 and divided them into two groups: before (Era 1, n = 19) and after (Era 2, n = 33) the initiation of HF-PCT activities in June 2015. Compared to Era 1, Era 2 showed a decrease in invasive procedures, an increase in opioid and non-intubating sedative use for symptom relief, improved quality of meals at the end of life, and an increase in participation in EOLC discussions. The administration of artificial nutrition in the final three days was associated with non-ischemic cardiomyopathy etiology, the number of previous hospitalizations for HF, and multidisciplinary EOLC discussion support. HF-PCT activities may provide an opportunity to discuss EOLC with patients, reduce the burden of physical and psychological symptoms, and shift the goals of end-of-life nutritional intake to ensure comfort and quality of life.