RESULTS OF IRRADIATION IN CANCER OF THE LIP,TONGUE AND EAR

Cancer of the lip: The primary lesion can be controlled by irradiation in approximately 80 per cent of cases. For lesions with metastases there is only about a 25 per cent chance of five-year arrest (irradiation of the primary lesion followed by excision of involved nodes).Cancer of the tongue: Lesions in the anterior two-thirds are controllable by irradiation in about 50 per cent of cases if the nodes are not involved; the salvage is only about 15 per cent if the nodes are involved (nodes treated surgically). Lesions in the posterior third of the tongue are seldom controlled in the author''s experience.Cancer of the ear (auricle): Five-year arrest of basal-cell lesions should be attained by irradiation in about 80 per cent of cases; of squamous-cell lesions in about 60 per cent. If the lesion is extensive, radiation does not offer a superior cosmetic result to operation and entails danger of late chondronecrosis. Therefore extensive lesions are probably best treated surgically. In either event, it appears probable that results of irradiation can be improved by the use of more adequate fields and greater fractionation.     

Results of irradiation in cancer of the lip,tongue and ear

CANCER OF THE LIP: The primary lesion can be controlled by irradiation in approximately 80 per cent of cases. For lesions with metastases there is only about a 25 per cent chance of five-year arrest (irradiation of the primary lesion followed by excision of involved nodes). CANCER OF THE TONGUE: Lesions in the anterior two-thirds are controllable by irradiation in about 50 per cent of cases if the nodes are not involved; the salvage is only about 15 per cent if the nodes are involved (nodes treated surgically). Lesions in the posterior third of the tongue are seldom controlled in the author's experience. CANCER OF THE EAR (AURICLE): Five-year arrest of basal-cell lesions should be attained by irradiation in about 80 per cent of cases; of squamous-cell lesions in about 60 per cent. If the lesion is extensive, radiation does not offer a superior cosmetic result to operation and entails danger of late chondronecrosis. Therefore extensive lesions are probably best treated surgically. In either event, it appears probable that results of irradiation can be improved by the use of more adequate fields and greater fractionation.     

Experience of proton stereotactic therapy for cerebral arteriovenous malformations in children

The authors present the results of proton stereotactic therapy (using continuous double-axis pendulum irradiation) in 27 children with cerebral arteriovenous malformations (AVM). At the moment of therapy, the children's age was 6 to 15 years. The volume of AVM was 0.2 to 31.2 cm3. The absorbed doses in the maximum of a dose field were 40 to 80 Gy. Complete AVM obliteration (the mean volume in the group was 3.03 cm3) was obtained in 11 (41%) patients. A 50% or more reduction in AVM volume (mean volume, 10.6 cm3) was seen in 8 (30%) patients. There was a less than 50% reduction in AVM volumes (mean volume 9.6 cm3) in 2 (7%) patients and no effect could be achieved in 6 (22%) (mean AMV volume 19.7 cm3).     

Axon response to guidance cues is stimulated by acetylcholine in Caenorhabditis elegans

Gradients of acetylcholine can stimulate growth cone turning when applied to neurons grown in culture, and it has been suggested that acetylcholine could act as a guidance cue. However, the role acetylcholine plays in directing axon migrations in vivo is not clear. Here, we show that acetylcholine positively regulates signaling pathways that mediate axon responses to guidance cues in Caenorhabditis elegans. Mutations that disrupt acetylcholine synthesis, transportation, and secretion affect circumferential axon guidance of the AVM neuron and in these mutants exogenously supplied acetylcholine improves AVM circumferential axon guidance. These effects are not observed for the circumferential guidance of the DD and VD motor neuron axons, which are neighbors of the AVM axon. Circumferential guidance is directed by the UNC-6 (netrin) and SLT-1 (slit) extracellular cues, and exogenously supplied acetylcholine can improve AVM axon guidance in mutants when either UNC-6- or SLT-1-induced signaling is disrupted, but not when both signaling pathways are perturbed. Not in any of the mutants does exogenously supplied acetylcholine improve DD and VD axon guidance. The ability of acetylcholine to enhance AVM axon guidance only in the presence of either UNC-6 or SLT-1 indicates that acetylcholine potentiates UNC-6 and SLT-1 guidance activity, rather than acting itself as a guidance cue. Together, our results show that for specific neurons acetylcholine plays an important role in vivo as a modulator of axon responses to guidance cues.     

Recovery after surgery of the spinal N24 SEP in dural arteriovenous malformation of the dorsal cord

We studied somatosensory evoked potentials (SEPs) to tibial nerve stimulation in two patients suffering from dorsal dural arteriovenous malformation (AVM). We found in both patients abnormalities in the lumbar N24 potential and in the cortical P40 response. After surgical removal of the AVM, the N24 recovered in both patients. Cord lesions probably occur in patients with dural AVM because of a theft of blood through the fistula; N24 recovery may therefore be associated with a restoration of blood supply after surgery. The N24 recovery in our patients with dural AVM suggests that the abnormality of this potential does not necessarily reflect irreversible damage to the Jumbo-sacral cord and that the N24 recording can be useful in post-surgical monitoring.     

Investigation of the link between avian vacuolar myelinopathy and a novel species of cyanobacteria through laboratory feeding trials

Avian vacuolar myelinopathy (AVM) is a neurologic disease affecting Bald Eagles (Haliaeetus leucocephalus), American Coots (Fulica americana), and other birds in the southeastern United States. The cause of the disease has not yet been determined, although it is generally thought to be a natural toxin. Previous studies have linked AVM to aquatic vegetation, and the current working hypothesis is that a species of cyanobacteria growing epiphytically on that vegetation is producing a toxin that causes AVM. Surveys of epiphytic communities have identified a novel species of cyanobacteria in the order Stigonematales as the most likely suspect. The purpose of this study was to further examine the relationship between the suspect Stigonematales species and induction of AVM, by using animal feeding trials. Adult Mallards and domestic chickens were fed aquatic vegetation from two study sites containing the suspect cyanobacterial epiphyte, as well as a control site that did not contain the Stigonematales species. Two trials were conducted. The first trial used vegetation collected during mid-October 2003, and the second trial used vegetation collected during November and December 2003. Neither treatment nor control birds in the first trial developed AVM lesions. Ten of 12 treatment Mallards in the second trial were diagnosed with AVM, and control birds were not affected. This study provides further evidence that the novel Stigonematales species may be involved with AVM induction, or at the least it is a good predictor of AVM toxin presence in a system. The results also demonstrate the seasonal nature of AVM events.     

Low-Dose radiation therapy for benign pathologies

Radiotherapy (RT) has always been a mainstay for malignant tumors therapy, but it is also used for benign pathology. The application of low or intermediate doses of RT has been widely studied. This topic was presented and discussed in the last XX GOCO (Grup Oncològic Català-Occità) meeting. The aim of this article is to review the indications of low dose irradiation (LD-RT), total dose and different fractionations, the public to whom it can be directed, and to offer an analysis about secondary effects. We believe it can be useful not only for radiation oncologists, but for other physicians to consider this option for future patients.     

The role of radiation therapy for carcinoma of the lung

A large proportion of patients with carcinoma of the lung may benefit from the use of radiation therapy. Operable patients have not been shown to benefit from preoperative irradiation, but postoperative irradiation has improved survival in those found to have involvement of hilar or mediastinal lymph nodes. Radiation therapy is the only potentially curative treatment for patients who are inoperable, but do not have distant metastasis. Control of the local tumor is very dependent upon dose-fractionation-time relationships. Patients who are relatively asymptomatic, i.e., they have a high performance status, are curable if treated promptly with radiation therapy. Small cell carcinoma requires both radiation therapy and chemotherapy. The optimal method of combining the two modalities is yet to be determined, but prophylactic cranial irradiation is necessary to control microscopic metastases that are not affected by systemic chemotherapy, and thoracic irradiation is necessary to give the highest probability of control of the primary tumor. Prophylactic cranial irradiation has also been shown to reduce the frequency of brain metastasis in patients with squamous carcinoma, large cell carcinoma, and adenocarcinoma; it may become more important in these cell types when more effective chemotherapy is developed.     

Attempts to identify the source of avian vacuolar myelinopathy for waterbirds

Attempts were made to reproduce avian vacuolar myelinopathy (AVM) in a number of test animals in order to determine the source of the causative agent for birds and to find a suitable animal model for future studies. Submerged vegetation, plankton, invertebrates, forage fish, and sediments were collected from three lakes with ongoing outbreaks of AVM and fed to American coots (Fulica americana), mallard ducks and ducklings (Anas platyrhynchos), quail (Coturnix japonica), and laboratory mice either via gavage or ad libitum. Tissues from AVM-affected coots with brain lesions were fed to ducklings, kestrels (Falco sparverius), and American crows (Corvus brachyrhynchos). Two mallards that ingested one sample of Hydrilla verticillata along with any biotic or abiotic material associated with its external surface developed brain lesions consistent with AVM, although neither of the ducks had clinical signs of disease. Ingestion of numerous other samples of Hydrilla from the AVM affected lakes and a lake with no prior history of AVM, other materials (sediments, algae, fish, invertebrates, and water from affected lakes), or tissues from AVM-affected birds did not produce either clinical signs or brain lesions in any of the other test animals in our studies. These results suggest that waterbirds are most likely exposed to the causative agent of AVM while feeding on aquatic vegetation, but we do not believe the vegetation itself is the agent. We hypothesize that the causative agent of AVM might either be accumulated by aquatic vegetation, such as Hydrilla, or associated with biotic or abiotic material on its external surfaces. In support of that hypothesis, two coots that ingested Hydrilla sampled from a lake with an ongoing AVM outbreak in wild birds developed neurologic signs within 9 days (ataxia, limb weakness, and incoordination), and one of two coots that ingested Hydrilla collected from the same site 13 days later became sick and died within 38 days. None of these three sick coots had definitive brain lesions consistent with AVM by light microscopy, but they had no gross or histologic lesions in other tissues. It is unclear if these birds died of AVM. Perhaps they did not ingest a dose sufficient to produce brain lesions or the lesions were ultrastructural. Alternatively, it is possible that a separate neurotoxic agent is responsible for the morbidity and mortality observed in these coots.     

Voltage-gated calcium channels direct neuronal migration in Caenorhabditis elegans

Calcium signaling is known to be important for regulating the guidance of migrating neurons, yet the molecular mechanisms underlying this process are not well understood. We have found that two different voltage-gated calcium channels are important for the accurate guidance of postembryonic neuronal migrations in the nematode Caenorhabditis elegans. In mutants carrying loss-of-function alleles of the calcium channel gene unc-2, the touch receptor neuron AVM and the interneuron SDQR often migrated inappropriately, leading to misplacement of their cell bodies. However, the AVM neurons in unc-2 mutant animals extended axons in a wild-type pattern, suggesting that the UNC-2 calcium channel specifically directs migration of the neuronal cell body and is not required for axonal pathfinding. In contrast, mutations in egl-19, which affect a different voltage-gated calcium channel, affected the migration of the AVM and SDQR bodies, as well as the guidance of the AVM axon. Thus, cell migration and axonal pathfinding in the AVM neurons appear to involve distinct calcium channel subtypes. Mutants defective in the unc-43/CaM kinase gene showed a defect in SDQR and AVM positioning that resembled that of unc-2 mutants; thus, CaM kinase may function as an effector of the UNC-2-mediated calcium influx in guiding cell migration.     

Skin-sparing mastectomy and radiotherapy: an update

Despite the lack of randomised controlled trials and paucity of the published data, the current evidence suggests that the post-mastectomy radiation therapy (PMRT) does not represent a contraindication to skin-sparing mastectomy (SSM) and immediate breast reconstruction (IBR) in the multidisciplinary setting. Although PMRT is associated with a higher incidence of complications, a satisfactory cosmetic outcome can be achieved in most patients. Radiation has a deleterious effect on autologous flap reconstruction that relies on fat for volume replacement such as the deep inferior epi-gastric perforator (DIEP) flap reconstruction and this method of reconstruction should be delayed until RT is completed. Until better methods of RT delivery are developed to minimise complications, women at high risk of requiring PMRT, can be safely offered SSM and IBR with a sub-pectoral saline-filled tissue expander and this can be replaced with a permanent prosthesis or converted into an autologous flap reconstruction after the completion of RT. Any capsule formation can be surgically treated at this stage. This new concept, known as immediate-delayed reconstruction, can avoid the cosmetic and RT delivery problems that can occur after IBR.Furthermore, prior RT does not represent a contra-indication to SSM and IBR, however it increases the incidence of complications.     

Sensitivity of human diploid fibroblast cell strains from various genetic disorders to acute and protracted radiation exposure

The cytotoxic effect of acute X irradiation was studied by a colony formation assay in 114 human skin fibroblast cell strains from 31 apparently normal individuals and 83 patients with a variety of genetic disorders possibly associated with in vitro hypersensitivity to ionizing radiation. The effect of protracted exposure to beta radiation from tritiated water (HTO) was examined in parallel experiments in 65 of these strains. The disorders included neurological diseases and syndromes characterized by an increased susceptibility to spontaneous and radiation-induced cancer. Homozygous ataxia telangiectasia and Nijmegen break syndrome cells were highly sensitive to both types of radiation. However, the response of cells from the other genetic disorders fell within the broad range characteristic of normal cell strains. While HTO may be useful as a quantitative method for determining the cytotoxic response of human diploid cells to ionizing radiation, the present results indicate that it does not offer a more sensitive assay than acute X irradiation for detecting minor degrees of hypersensitivity.     

Synthesis and photochemical properties of nitro-naphthyl chromophore and the corresponding immunoglobulin bioconjugate

Synthesis, photochemistry, and biomolecular caging properties of a new chromophore namely 3-nitro-2-naphthalenemethanol are described. This chromophore is photoexcitable with photons in 350-400 nm range and in several solvents including aqueous medium. On irradiation, it gives the expected nitroso-aldehyde photoproduct with high quantum yield (0.6-0.8). Further, it can be conveniently coupled to the amino residues of immunoglobulin (IgG) using diphosgene. Irradiation of the resulting IgG-nitronaphthyl chromophore bioconjugate at 380 nm causes photorelease of IgG as evidenced by Protein-A affinity binding studies. The bioconjugate showed low level of binding to Protein-A. However, the binding increases after irradiation and, thus, modifies the Fc site of the IgG. Electrophoresis studies of the irradiated bioconjugate show that IgG does not undergo fragmentation or molecular weight change under the irradiation conditions. Thus, 3-nitro-2-naphthalenemethanol can be used as a photocaging agent under physiological conditions at wavelengths, which does not cause significant damage to the biomolecule. The work provides new directions for the development of organic chromophores for biomolecular caging applications.     

Attempts to reproduce vacuolar myelinopathy in domestic swine and chickens

Avian vacuolar myelinopathy (AVM) was first recognized as a cause of bald eagle (Haliaeetus leucocephalus) mortality in 1994 in Arkansas (USA) and has since caused over 90 bald eagle and numerous American coot (Fulica americana) mortalities in five southeastern states. The cause of AVM remains undetermined but is suspected to be a biotoxin. Naturally occurring AVM has been limited to wild waterbirds, raptors, and one species of shorebird, and has been reproduced experimentally in red-tailed hawks (Buteo jamaicensis). In this study, chickens and swine were evaluated for susceptibility to vacuolar myelinopathy with the intent of developing animal models for research and to identify specific tissues in affected coots that contain the causative agent. Additionally, submerged, aquatic vegetation, primarily hydrilla (Hydrilla verticillata), and associated material collected from a reservoir during an AVM outbreak was fed to chickens in an effort to reproduce the disease. In two separate experiments, six 4-wk-old leghorn chickens and ten 5-wk-old leghorn chickens were fed coot tissues. In a third experiment, five 3-mo-old domestic swine and one red-tailed hawk, serving as a positive control, were fed coot tissues. In these experiments, treatment animals received tissues (brain, fat, intestinal tract, kidney, liver, and/or muscle) from coots with AVM lesions collected at a lake during an AVM outbreak. Negative control chickens and one pig received tissues from coots without AVM lesions that had been collected at a lake where AVM has never been documented. In a fourth experiment, eight 3-wk-old leghorn chickens were fed aquatic vegetation material. Four chickens received material from the same lake from which coots with AVM lesions were collected for the previous experiments, and four control chickens were fed material from the lake where AVM has never been documented. Blood was collected and physical and neurologic exams were conducted on animals before and once per week during the trials. All animals were sacrificed and necropsies were performed on Day 29 of feeding, with the exception of one treated chicken that was sacrificed and necropsied on Day 15 of feeding. Microscopic lesions of vacuolar myelinopathy were present in the red-tailed hawk and five chickens that received a mixture of all tissues and two chickens that received only gastrointestinal tissues of coots with AVM lesions. Three of four treated chickens in the aquatic vegetation trial developed vacuolar lesions. None of four treatment pigs or any of the negative control animals developed vacuolar lesions. Chickens are susceptible to AVM and may serve as a useful animal model for future studies. Swine may be refractory to AVM or not affected by AVM at the same dose as are chickens and red-tailed hawks. The causative agent of AVM in affected coots is associated with the gastrointestinal tissues. Furthermore, AVM can be reproduced in chickens via ingestion of aquatic vegetation and associated materials collected from a lake during an AVM outbreak. The cause of AVM is most likely present in the materials associated with submerged vegetation because the vegetation itself (hydrilla) was the same at our AVM-positive and AVM-negative sites.     

Experimental vacuolar myelinopathy in red-tailed hawks

Avian vacuolar myelinopathy (AVM) was recognized in 1994 as a cause of wild bird mortality when 29 bald eagles (Haliaeetus leucocephalus) succumbed to the disease at DeGray Lake, Arkansas (USA). The cause of AVM and its source remain undetermined despite extensive diagnostic and research investigations. Two years later, when AVM killed 26 eagles in the same area in Arkansas, it became apparent that American coots (Fulica americana) had identical neurologic signs and lesions, and it was hypothesized that eagles acquired AVM via ingestion of affected coots. In order to test this hypothesis, we fed coot tissues (brain, liver, kidney, muscle, fat, and intestinal tract) to rehabilitated, non-releasable red-tailed hawks (Buteo jamaicensis). Five hawks received tissues from coots with AVM lesions, and one hawk received tissues from coots without brain lesions that had been collected at a site where AVM never has been documented. All hawks received 12-70 g/day (mean = 38 g) of coot tissues for 28 days. All six hawks remained clinically normal during the study. The birds were euthanatized on day 29 and microscopic lesions of AVM were found in all hawks that received tissues from affected coots, but not in the hawk that received tissues from unaffected coots. This marks the first time that AVM has been produced in birds under laboratory conditions and proves that birds of prey can acquire AVM via ingestion of tissues from affected coots.     

Posterior hypothalamus action on gastric secretion (author's transl)]

Three groups of cats with surgically created total gastric pouches were employed in this experiment. They were divided as follows: in one group the innervation of the pouch was left intact; in another group the symphathetic innervation of the pouch was removed; and in the third group the pouch was completely denervated. It was seen that an infusion of histamine induced gastric secretion in all three groups. And when the secretion became constant it proved to be less acidic and more abundant in the sympathectomized group and also in the group that had suffered complete denervation. It was observed now that stimulating the posterior hypothalamus of the innervated group produced, in all of the cats, a decrease in the amount of acid secreted per unit of time. Consequently, it was seen that a symphathectomy did not eliminate the gastric effects produced when the posterior hypothalamus was stimulated. Specifically, stimulation of the posterior hypothalamus produced an increase in the amount of secretion rather than a decrease. The increase produced in these animals can be shown not to be due to irradiation of the anterior hypothalamus as the same response is obtained when a symphathectomy is combined with a vagotomy. It is, therefore, believed that it may be concluded that the Posterior hypothalamus does not produce its effect exclusively through its nervous pathways. It is believed its effect may possibly be mediated by an unknown substance liberated upon stimulation which then reaches the stomach by way of its blood supply.     

Recurrent pleomorphic adenoma of epipharynx following irradiation therapy

We present a case of a 67-year-old female patient having a pleomorphic adenoma of epipharynx with intact fibrous capsula, which despite its benignity recurred and, moreover, responded quite well to irradiation therapy. The patient, at first, refused any therapy. Three years later, when the CT showed tumor enlargement she accepted only irradiation therapy, resulting in significant reduction of tumor size. Five years later the tumor recurred but without malignant transformation. She still refused surgery, but accepted re-irradiation therapy. After a three-year follow-up the patient has no symptoms of the tumor enlargement. This case shows that the irradiation therapy might be quite effective in the treatment of pleomorphic adenoma of epipharynx, but it is clear that much better results could be accomplished in combination with the surgery. In cases when the surgery is rejected or not possible because of the vicinity of the vital structures, we recommend the irradiation therapy as a therapy of the choice.     

Lack of specificity of chromosome breaks resulting from radiation-induced genomic instability in Chinese hamster cells

In V79 Chinese hamster cells, radiation-induced genomic instability results in a persistently increased frequency of micronuclei, dicentric chromosomes and apoptosis and in decreased colony-forming ability. These manifestations of radiation-induced genomic instability may be attributed to an increased rate of chromosome breakage events many generations after irradiation. This chromosomal instability does not seem to be a property which has been inflicted on individual chromosomes at the time of irradiation. Rather, it appears to be secondary to an increased level of non-specific clastogenic factors in the progeny of most if not all irradiated cells. This conclusion is drawn from the observations presented here, that all the chromosomes in surviving V79 cells are involved in the formation of dicentric chromosome aberrations 1 or 2 weeks after irradiation with about equal probability if corrections are made for chromosome length. Received: 5 March 1998 / Accepted in revised form: 1 July 1998     

Virdee's challenges

Satnam Virdee’s Racism, Class and the Racialized Outsider is a book of great merit. But it contains a remarkable paradox: it argues strongly against racism and nationalism, but it does so in an insular way. Now and then there is mention of other parts of the world, but the book does not as such look beyond England’s boundaries. This implies at least two important challenges for further work. First, it appears that Virdee still remains imprisoned in methodological nationalism (not to be confused with political nationalism). Second, Virdee does not yet offer a structural analysis of working-class racism. An additional point is that Virdee’s analysis lacks an explicit gender perspective. The connection between fragile masculinities and (anti-)racist attitudes is not explored. These marginalia are not intended as objections to Virdee’s work. He has accomplished quite a lot and we can build on his work.     

The effect of laser activation of 5,10,15,20-tetra-sulphophenyl-porphyrin loaded in K562 cells and human normal mononuclear cells

Photodynamic therapy (PDT) is a relatively new type of treatment in cancer, based on a photosensitizer, visible light and molecular oxygen. Reactive oxygen species are generated, causing tumor cells death by apoptosis or necrosis. Significant nowadays research efforts are focused on finding new photosensitizers with antineoplastic activity and an acceptable toxicological profile. Although consistent information exists regarding PDT in solid tumors, relatively few data are available for PDT of blood cancers. Therefore, we carried out a comparative study on lymphoblastic K562 cells and human normal peripheral blood mononuclear cells (PBMC) treated at a density of 2 x 10(5) cells/mL with 5,10,15,20-tetra-sulphophenyl-porphyrin (TSPP) and then irradiated with He-Ne laser light (lamda = 632.8 nm). The following cell functions were investigated: viability, multiplication, RNA synthesis, total RNA levels and apoptosis. After irradiation, the viability of TSPP-loaded tumor cells decrease, the multiplication rate and the total RNA level are drastically reduced and cells undergo apoptosis. TSPP alone loaded into cells but not activated by irradiation, does not affect these cell parameters. Human normal PBMC subjected to TSPP loading and laser-irradiation develop a different cellular response, their viability and proliferative capacity not being altered by experimental PDT. Accordingly, it appears that TSPP is a non-aggressive compound for cellular physiology and becomes cytotoxic only by irradiation; moreover laser-activated TSPP affects only cells that have a tumoral pattern.