Intravenous Remifentanil Analgaesia for an Obstetric Patient with Type I Neurofibromatosis and a Factor V Leiden Mutation.

Type I neurofibromatosis is characterised by altered skin pigmentation and the growth of benign tumours, particularly along the peripheral nerves and central nervous system. We report a 36-year-old primigravida woman in labour who was admitted to the obstetric suite of the Hospital Sant Joan de Déu, Barcelona, Spain, in 2007 with hypothyroidism, type I neurofibromatosis and a factor V Leiden mutation. Due to a lack of cranial and spinal imaging data, an epidural was not indicated; instead, continuous intravenous remifentanil analgaesia was administered. The remifentanil infusion was self-titrated by the patient using a visual analogue scale, with the dosage ranging from 0.01 to 0.25 µg/kg/minute. Due to rotational dystocia, Kjelland-type forceps were used during the delivery. After birth, the infant was found to have Apgar scores of 9 and 10, with no maternal or neonatal adverse effects observed. Although still controversial, remifentanil may be a successful alternative for analgaesia in similar cases; however, the specific risks and benefits for each patient should be considered prior to administration.

Pentazocine-induced fibrous myopathy and localized neuropathy.

A 47 year-old woman who had a 4-year history of intramuscular pentazocine injections in the lower extremities, developed gradual stiffness and weakness of the lower extremities. The thigh and buttock muscles were "wooden-hard" on palpation. The skin was hard, shiny and hairless. Associated clinical and electrophysiological polyradiculopathy and multiple mononeuropathy of the lower extremities were observed. Imaging studies showed calcification and fibrosis of the involved muscles. Muscle biopsy revealed fibrous myopathy. Caution in longterm usage and early recognition of pentazocine toxicity as a neuromuscular complication are important in order to prevent irreversible drug-induced fibrous myopathy and localized neuropathy.

neu proto-oncogene mutation is specific for the neurofibromas in a N-nitroso-N-ethylurea-induced hamster neurofibromatosis model but not for hamster melanomas and human Schwann cell tumors.

Point mutations of the transmembrane domain coding region of the neu proto-oncogene in N-nitroso-N-ethylurea-induced hamster neurofibromas were found at high frequency (93%; 14 of 15). They involved codons 659 as well as 658, the latter not having been reported previously in rat tumors. The mutational change was seen even in the early stage neurofibroma. On the other hand, no mutations were detected in melanomas or Wilms' tumors induced in the same N-nitroso-N-ethylurea-treated animals, even when the melanomas demonstrated extensive schwannian differentiation. Moreover, any human Schwann cell tumors including neurofibroma, schwannoma, and malignant schwannoma did not show the mutation of c-erbB-2 gene (0 of 34), which is homologous to the hamster neu. Since high expression of neu mRNA is evident in the hamster Schwann cell at the late gestational and neonatal stages, transplacental administration of N-nitroso-N-ethylurea is considered to interact directly to carcinogenesis of the hamster Schwann cell through neu gene mutation.

Transplacental induction of peripheral nervous tumor in the Syrian golden hamster by N-nitroso-N-ethylurea. A new animal model for von Recklinghausen's neurofibromatosis.

Multiple peripheral nervous tumors were induced in 45 of 60 (75.0%) Syrian golden hamsters by transplacental administration of N-ethyl-N-nitro-sourea. Moreover, melanomas, pheochromocytomas, and Wilms' tumors developed in six (10.0%), three (5.0%), and 13 (21.7%) animals, respectively. The histologic, immunohistochemical, and electron microscopic findings of the peripheral nervous tumors were similar to those of human neurofibroma, and their growth pattern and distribution resembled those of human von Recklinghausen's neurofibromatosis (VRNF). The occurrence of melanoma, pheochromocytoma, and proliferative foci of melanin-containing cells in neurofibroma suggests that the targets of ENU in hamsters are the neural crest-derived cells. With its high incidence of Wilms' tumor, the hamster with ENU-induced tumors is considered to be a good animal model for human neurocristopathy, including VRNF.

Exposure of newborn mice to adenosine causes neural crest dysplasia and tumor formation.

In the first part of this paper, we show that intraperitoneal injection of adenosine into newborn mice causes multiple neural crest tumors, neural crest hyperplasia, and heterotopic melanin pigmentation. In the second part, we review published data to propose (1) that microtubule proteins, phosphorylated through the action of calmodulin-dependent kinase and cyclic adenosine monophosphate and the adenosine A2 receptor of neural crest cells, may participate in neurotransmission and (2) that at least some neural crest tumors may be associated with disorders of neurotransmission in embryonic neural crest cells.

Induction of malignant peripheral nerve sheath tumors in European hamsters with 1,1-dimethylhydrazine (UDMH).

A rate of up to 43% of malignant peripheral nerve sheath tumors (PNST) was induced in European hamsters (EH) after weekly s.c. administration of 1,1-dimethylhydrazine (UDMH). The overall neoplastic response in the treated EH was also elevated as compared to the untreated controls. Histologically, the malignant PNST were neurofibrosarcomas and melanotic as well as unpigmented schwannomas. The occurrence of melanotic schwannomas is briefly discussed with regard to the histogenesis of this rare tumor type.

An evaluation of reports of dioxin exposure and soft tissue sarcoma pathology among chemical workers in the United States.

A review of employment records and tissue specimens of seven workers, reported previously as having occupational dioxin exposure and soft tissue sarcomas, confirms that four workers had employment of 2 to 19 years in the production of 2,4,5-trichlorophenoxyacetic acid (2,4,5-T) or trichlorophenol, products contaminated with 2,3,7,8-tetrachlorodibenzodioxin, the most toxic dioxin isomer. Of these individuals, two have confirmed soft tissue sarcomas. In addition three individuals who worked for companies which made 2,4,5-T also have confirmed soft tissue sarcomas. Their employment records do not show specific assignment to 2,4,5-T or trichlorophenol departments; however, one individual worked for 10 d in the production of pentachlorophenol, which is contaminated with different isomers of dioxin. Methodological problems are discussed which must be addressed in the epidemiologic evaluation of the outcome of soft tissue sarcoma.

Transplacental teratogenic and carcinogenic effects in rabbits chronically treated with N-ethyl-N-nitrosourea.

Pregnant rabbits of two partially inbred strains, WH/J and IIIVO/J, were given ten consecutive daily ip injections of 10 mg N-ethyl-N-nitrosourea (ENU)/kg dissolved in trioctanoin starting on either day 10, 15, or 18 of gestation. Of 7 WH/J progeny weaned, 3 developed primary renal tumors at 6.8 +/- 0.6 months of age (mean +/- SE). Similarly, of 12 IIIVO/J progeny weaned, 10 developed primary renal tumors at 6.3 +/- 0.6 months of age (mean +/- SE); in addition, 1 fibroblastic osteosarcoma and 5 neurofibromas, some associated with neurilemma cysts, were observed. Renal tumors were nephroblastomas , which appeared to develop within small renal cortical cysts. The frequency of tumor induction for each strain was similar to that in our previous experiments with acute administration of ENU and ethyl-urea plus NaNO2, but the latency period (6.4 +/- 0.5 mo) was almost doubled. In addition, chronic treatment of ENU induced teratogenic effects. In a number of these progeny, a disproportionate stunting or miniaturization was evident, the frequency of which increased with the age of the treated fetuses. In contrast, holes were found in the parietal bones at birth, but with a frequency that decreased with increasing fetal age at time of treatment. No teratogenic effects were observed in the controls.

[Antigenicity of a chemically induced neurogenic rat sarcoma (author's transl)]. / Uber die Antigenität eines chemisch induzierten neurogenen Sarkoms der Ratte.

A neurogenic sarcoma was induced in the plexus brachialis of a male Long-Evans rat by administration of N-methyl-N-nitrosourea in the drinking water. The tumor was established in vitro and designated 76LE-NS-369. Cells from tissue culture grew as tumors when isografted in young rats. 76LE-NS-369 cells did not react with antiserum directed against gliaspecific S-100 protein. We used the cultured cells as target cells, and found specific antibodies in the sera of tumor-bearing and immunized rats by indirect fluorescent antibody stain and a complement-dependent antibody-mediated microcytotoxicity assay. In immunization experiments, incubation of tumor cells with Vibrio cholerae neuraminidase yielded higher antibody titers than an antigen preparation with untreated cells. Incubation with neuraminidase enhanced the sensitivity of tumor cells to antibody and complement in vitro, whereas trypsinized cells showed complete loss of reactivity with autologous antisera. The specificity of antisera was tested by absorption with tumor, lyophilized rat whole body and rat nerve tissues.

[The treatment of ptyalism in children with cerebral lesions (author's transl)]. / Glioblastom und Neurofibrom nach Lost-Enwirkung

The cytotoxic and alkylating substance, mustard gas, causes both acute poisoning and also damage to numerous organs following chronic exposure. Especially important is the carcinogenic effect, also confirmed in humans. 34 years after occupational exposure to mustard gas with many intoxication episodes, a former munition-worker died of a glioblastoma; two years before his death a neurofibroma was detected in the thorax and removed by operation. The causal connection between the mustard gas exposure and the development of two neurogenic tumors rests on the statistically significantly raised frequency of malignant tumors and the established psychic changes in former workers with mustard gas and especially on the production of malignant tumors of the central nervous system in experimental animals with alkylating nitrosamines.

Carcinogenicity of nitrosation products of ephedrine, sarcosine, folic acid, and creatinine.

Carcinogenic activity of several synthetic N-nitroso compounds was evaluated in C57BL/6J X C3HeB/FeJ F1 mice. Test substances, suspended in trioctanoin, were injected i.p. in three equal doses given on Days 1, 4, and 7 after birth and animals were held without further treatment for up to 85 weeks. Nitrosoephedrine at a total dose of 600 mg/kg induced metastasizing liver cell carcinomas in 28 of 30 animals. Nitrososarcosine (225 mg/kg) induced similar tumors in 8 of 14 animals. Nitrosofolic acid (375 mg/kg) induced lung adenocarcinomas in 4 of 28 mice. Creatinine-5-oxime (600 mg/kg) showed no evidence of carcinogenic activity. Diethylnitrosamine (12 mg/kg given in four doses), included as a positive control, caused metastasizing liver cell tumors in 23 of 25 animals.

Carcinogenesis in vitro. II. Chemical transformation of diploid human cell cultures: A rare event.

Seventy-five diploid human cell s-rains were subjected to a number of chemical carcinogens, including urethane and polycyclic hydrocarbons. In most cases, no visible morphological alterations were induced by any treatment. Development of morphologically altered foci was noticed in urethane-treated cultures derived from a patient with von Recklinghausen's disease. This disease is transmitted by an autosomal dominant gene, and has a high rate of spontaneous transformation of neurofibromas to neurofibrosarcomas. Attempts to isolate continuous cell lines from altered foci were successful in only two of several attempts. These continuous cell lines demonstrate altered morphology, loss of contact inhibition, accelerated growth rate, and have attained over 240 generations in a period of 140 weeks. Untreated control cultures became terminal by the 20th generation. Giemsa banding procedures showed that the chromosomal complement consisted of heteroploid human chromosomes. A second diploid cell strain derived from the above patient's sibling, also suffering from von Recklinghausen's disease, likewise was morphologically altered by urethane. Chemical transformation of human cells is difficult to induce; however, selection of genetically predisposed cells and prolonged, intermittent, and repeated chemical treatment may be important factors in achieving transformation.

An experimental study of intraoral carcinogenesis in rats.

A new method has been devised for preparing artificial cecal pouches lined with mucous epithelium in the lower lips of Wistar and Sprague-Dawley rats in order to make carcinogens act continuously for a long time in the oral mucosa. When a 0.5 per cent mineral oil solution of DMBA, a crystal of MC, and a crystal of NG were administered, squamous-cell carcinoma, carcinoma in situ, papilloma, adenoma sebaceum. neurofibroma, fibroma, hemangiosarcoma, hemangiosarcoma, hemangioma, and lymphangioma were successfully produced in the oral mucosa of rats. In addition, interesting findings were obtained concerning tissue changes in the process of carcinogensis in the mucous epithelium.