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CT and MR findings in neoplastic perineural spread along the vidian nerve.

The aims of this article are to describe the findings of perividian tumor spread and to compare the accuracy of MRI and CT in diagnosing perineural metastasis along the vidian nerve. Moreover, the frequency of perividian metastasis in patients with head and neck cancer was evaluated. The CT and MR examinations of 98 consecutive untreated patients with histologically proven head and neck cancer were retrospectively reviewed. We considered as criteria for perineural tumor spread along the vidian nerve the following CT and MR findings: For CT (a) enlargement of the pterygoid canal, (b) erosion of its bony wall, and (c) obliteration of its normal fatty content; and for MR (a) enlargement of the vidian nerve, (b) enhancement of the nerve, and (c) obliteration of fat, particularly in the anterior part of the pterygoid canal. Ten patients met the selected criteria for perineural metastasis, which was bilateral in 3 patients, with a total of 13 vidian metastases. The CT scans demonstrated unilateral involvement of the vidian nerve in 9 patients. The MRI scans showed 13 perineural metastases. In 3 patients MR scans demonstrated involvement of four vidian nerves that appeared normal on CT examinations. The diagnostic difference between CT and MRI was statistically significant (Fisher's exact test; p = 0.04). Perineural spread along the vidian nerve is an event more frequent than previously reported and must be investigated with a careful imaging technique. Although a major limitation of our study is the lack of histological proof, the MR finding of a significant enhancement of the nerve, whether enlarged or normal in size, could be considered very suggestive of this kind of metastatic spreading, particularly if associated with simultaneous involvement of the neighboring structures (pterygopalatine fossa, foramen lacerum, trigeminal branches, etc.).

Adult↗

Epidural administration and analgesic spread: comparison of injection with catheters and needles.

This study was designed to investigate differences in epidural analgesic spread between catheter and needle injections in 48 patients with comparable physical characteristics. The spread of analgesia in the catheter injection group with a 0.24 ml.sec(-1) injection rate (n = 16) was 16.8 +/- 1.5 spinal segments and that in the needle injection group at the same injection rate (n = 16) was 12.5 +/- 1.8 spinal segments ( P < 0.01). Needle injection at the faster rate of 1.2 ml.sec(-1) (n = 16) produced a significantly greater spread of analgesia than with the 0.24 ml.sec(-1) rate through the needle (16.2 +/- 1.6 vs 12.5 +/- 1.8 spinal segments, P < 0.01). Thirteen of 16 patients receiving the fast needle injection complained of back compression or discomfort during the injection. The injection through an epidural catheter and the fast (1.2 ml.sec(-1)) injection through a needle produced extensive and equivalent epidural analgesic spread. However, because of patients discomfort with fast injection through the needle, the authors conclude that when using continuous epidural anesthesia, the initial injection of local anesthetic should be administered through the epidural catheter not the needle.

Journal Article↗

Topographic spread of inferior colliculus activation in response to acoustic and intracochlear electric stimulation.

The design of contemporary multichannel cochlear implants is predicated on the presumption that they activate multiple independent sectors of the auditory nerve array. The independence of these channels, however, is limited by the spread of activation from each intracochlear electrode across the auditory nerve array. In this study, we evaluated factors that influence intracochlear spread of activation using two types of intracochlear electrodes: (1) a clinical-type device consisting of a linear series of ring contacts positioned along a silicon elastomer carrier, and (2) a pair of visually placed (VP) ball electrodes that could be positioned independently relative to particular intracochlear structures, e.g., the spiral ganglion. Activation spread was estimated by recording multineuronal evoked activity along the cochleotopic axis of the central nucleus of the inferior colliculus (ICC). This activity was recorded using silicon-based single-shank, 16-site recording probes, which were fixed within the ICC at a depth defined by responses to acoustic tones. After deafening, electric stimuli consisting of single biphasic electric pulses were presented with each electrode type in various stimulation configurations (monopolar, bipolar, tripolar) and/or various electrode orientations (radial, off-radial, longitudinal). The results indicate that monopolar (MP) stimulation with either electrode type produced widepread excitation across the ICC. Bipolar (BP) stimulation with banded pairs of electrodes oriented longitudinally produced activation that was somewhat less broad than MP stimulation, and tripolar (TP) stimulation produced activation that was more restricted than MP or BP stimulation. Bipolar stimulation with radially oriented pairs of VP ball electrodes produced the most restricted activation. The activity patterns evoked by radial VP balls were comparable to those produced by pure tones in normal-hearing animals. Variations in distance between radially oriented VP balls had little effect on activation spread, although increases in interelectrode spacing tended to reduce thresholds. Bipolar stimulation with longitudinally oriented VP electrodes produced broad activation that tended to broaden as the separation between electrodes increased.

Acoustic Stimulation↗

Capsid protein genetic analysis and viral spread to the spinal cord in cats experimentally infected with feline calicivirus (FCV).

We investigated primitively the molecular basis of the neural spread of a feline calcivirus isolate (FCV-S) from the spinal cord of a cat that died after manifesting excitation. Experimental infections of cats with three clones from parent virus isolate FCV-S, isolated based on plaque size, were performed, and virus recovery from the spinal cord and the nucleotide and predicted amino acid sequences of the viral capsid protein region (ORF2) were compared. In the experimental infection with the one-time cloned virus (C1L1) isolated from a large plaque, the C1L1 was recovered from the spinal cord. In contrast, seven-times cloned C6L7 (from large plaque) and five-times cloned C5S2 (isolated from small plaque) were not recovered from the spinal cord. Genetic analysis of the capsid protein gene of the three viral clones revealed that four bases were different and two amino acids were different at positions 34 (Val in C6L7 and Ala in C1L1 and C5S2) and 46 (Leu in C6L7 and Pro in C1L1 and C5S2) between C6L7 (with large plaque) and C5S2 (with small plaque). The amino acid at position 434 of C1L1 was different from those of C6L7 and C5S2 (Gly in C1L1, D (Asp) in C6L7 and C5S2). From these results, the plaque size seemed not to be related to the spread of virus to the spinal cord. Clone C1L1, which spread to the spinal cord, had a difference of one amino acid from the other two clones, which may be related to the ability to spread to the spinal cord.

Amino Acid Sequence↗

Characterization of HPV-16 E6 DNA vaccines employing intracellular targeting and intercellular spreading strategies.

Human papillomavirus (HPV) E6 and E7 are consistently expressed and are responsible for the malignant transformation of HPV-associated lesions. Thus, E6 and E7 represent ideal targets for therapeutic HPV vaccine development. We have previously used the gene gun approach to test several intracellular targeting and intercellular spreading strategies targeting HPV-16 E7. These strategies include the use of the sorting signal of lysosome-associated membrane protein (LAMP-1), Mycobacterium tuberculosis heat shock protein 70 (HSP70), calreticulin (CRT) and herpes simplex virus type 1 (HSV-1) VP22 proteins. All of these strategies have been shown to be capable of enhancing E7-DNA vaccine potency. In the current study, we have characterized DNA vaccines employing these intracellular targeting or intercellular spreading strategies targeting HPV-16 E6 for their ability to generate E6-specific CD8+ T cell immune responses and antitumor effects against an E6-expressing tumor cell line, TC-1, in C57BL/6 mice. We found that all the intracellular targeting strategies (CRT, LAMP-1, HSP70) as well as the intercellular spreading strategy (VP22) were able to enhance E6 DNA vaccine potency, although the orientation of HSP70 linked to E6 antigen in the E6 DNA vaccine appears to be important for the HSP70 strategy to work. The enhanced E6-specific CD8+ T cell immune response in vaccinated mice also translated into potent antitumor effects against TC-1 tumor cells. Our data indicate that all of the intracellular targeting and intercellular spreading strategies that have been shown to enhance E7 DNA vaccine potency were also able to enhance E6 DNA vaccine potency.

Animals↗

Traveling waves and spread rates for a West Nile virus model.

A reaction-diffusion model for the spatial spread of West Nile virus is developed and analysed. Infection dynamics are based on a modified version of a model for cross infection between birds and mosquitoes (Wonham et al., 2004, An epidemiological model for West-Nile virus: Invasion analysis and control application. Proc. R. Soc. Lond. B 271), and diffusion terms describe movement of birds and mosquitoes. Working with a simplified version of the model, the cooperative nature of cross-infection dynamics is utilized to prove the existence of traveling waves and to calculate the spatial spread rate of infection. Comparison theorem results are used to show that the spread rate of the simplified model may provide an upper bound for the spread rate of a more realistic and complex version of the model.

Algorithms↗

Transregional spread of a single clone of methicillin-resistant Staphylococcus aureus between groups of drug users in Switzerland.

BACKGROUND: An epidemic spread of methicillin-resistant Staphylococcus aureus (MRSA) among intravenous drug users (IDUs) has been observed in Zurich. In the present study we investigated the situation in the Grisons, Switzerland. PATIENTS AND METHODS: We screened IDUs and their caregivers in medical and socio-therapeutical institutions in the Grisons for MRSA. Nose swabs were used for bacterial culture and pulsed-field gel electrophoresis for MRSA genotyping. RESULTS: A total of 191 nose swabs from 111 IDUs and 80 caregivers was analyzed. None of the caregivers was MRSA positive. Six IDUs were asymptomatic MRSA carriers (5.4%). They participated in the official heroin program (MRSA prevalence in this group 16%). The MRSA genotype was identical with the single clone found in IDUs in Zurich, strongly suggesting an epidemic spread. Decolonization was successful in two persons only. Persistence of MRSA in IDUs must therefore be assumed. CONCLUSION: We conclude that a single clone of MRSA, found in IDUs in Zurich, has spread to a distant region of Switzerland. A rigorous infection control program in all institutions with IDUs is necessary to prevent a further spread of MRSA.

Adult↗

Role of the conduction system in the endocardial excitation spread in the right ventricle.

The role of the Purkinje network in the excitation sequence in the endocardial surface of the right ventricle was studied using an isolated perfused canine preparation. The preparation was electrically stimulated at the proximal right bundle branch, and the activation time was mapped using contiguous bipolar electrodes or a microelectrode, or both. The earliest activation of muscle was observed at the junction between the ventricular septum and the free wall in front of the anterior papillary muscle. After the initial activation, the spread of ventricular muscle excitation in the free wall was essentially radial at a mean (+/- standard deviation) conduction velocity of 1.67 +/- 0.20 m/s. The activation of muscle in this area was almost always preceded by the activation of Purkinje fibers by 2 to 6 ms. Thus the Purkinje system was considered indispensable for the excitation spread in this area. In the lower third of the septum, the excitation sequence was essentially similar to that of the free wall, indicating a possible contribution of the fast conducting Purkinje system. In contrast, in the upper two thirds of the septum the activation of ventricular muscle spread from apex to base with a significantly delayed conduction velocity of 0.41 +/- 0.88 m/s, and it was not preceded by activation of Purkinje fibers, thus indicating the lack of involvement of the Purkinje system. Functional distribution of the anterior, posterior and lateral branches of the right bundle to the excitation spread of the right ventricular endocardial muscle was confirmed by the selective transection of one of these special conducting fibers, which suggested the etiologic significance of injury to each branch of the right bundle as a cause of various electrocardiographic patterns of incomplete right bundle branch block.

Action Potentials↗

Intramural spread of colon carcinoma. A pathologic study.

The results of a pathologic study of 42 colorectal cancers have been presented. Of the 42 lesions, only 2 demonstrated intramural spread. The maximum extent of intramural spread was 2 cm. In one case, intramural spread was in the distal direction. Thirty-six percent of the lesions were in the rectum or rectosigmoid, 19 percent were in the sigmoid colon, 19 percent were in the descending colon, 5 percent were in the transverse colon, and 21 percent were in the right side of the colon. Of the lesions, 14.2 percent were classified Dukes' A, 45.2 percent Dukes' B, and 35.7 percent Dukes' C. Two lesions showed widely disseminated disease. All were adenocarcinomas. Of the five low-lying Dukes' C lesions, three had positive distal lymph nodes. Based on a review of the literature and the findings of this study, a distal margin of resection of 2.5 cm is deemed acceptable. Patients with lesions clinically suspected to be Dukes' C, however, should undergo abdominoperineal resection in an attempt to eradicate distal intramural or lymphatic spread.

Adenocarcinoma↗

Spread of saphenous somatotopic projection map in spinal cord and hypersensitivity of the foot after chronic sciatic denervation in adult rat.

The left sciatic nerve was cut and ligated in adult rats (chronic denervation). Twenty-one days later the right sciatic nerve was cut and ligated (acute denervation). The somatotopic maps of the surviving intact saphenous nerves (left and right) were compared on day 21 by recording from single interneurons in the dorsal horn of the spinal cord. On the acute side saphenous mediated natural responses were observed only as far caudally as L3, while no natural responses were found in L4 and 5 (this silent zone in L4 and 5 had previously been sciatic territory). In contrast, after chronic sciatic denervation, L4 and L5 were not silent to natural stimulation as the saphenous natural responses had spread into the sciatic territory. Saphenous inputs always won the sciatic territory in L4 and L5 over competing thigh afferents after chronic sciatic denervation. Electrical stimulation of the saphenous nerve on the acute side produced unit responses all the way down to S1 (with no silent areas in L4 and 5). These electrically evoked unit responses in L4 to S1 of the acute side were called 'long range' pathways. There were no differences in 'long range' electrical responses in the acutely and chronically denervated cord. The caudal boundary for electrically evoked saphenous responses was S1 on both sides of the cord, and post stimulus histograms of unit responses were not statistically different on the two sides. Thus after chronic sciatic denervation natural responses mediated by saphenous spread caudally into sciatic territory, but electrically evoked responses did not change. Behaviorally, there was the expected spread of saphenous mediated responses from the medial toe and foot to more lateral regions after chronic sciatic denervation. Unexpectedly, there was an increase in sensitivity (hyperalgesia) of the medial toe and foot. We postulate that this increased sensitivity might be mediated by the spread of saphenous projections into L4 and L5 of the cord after chronic sciatic denervation. Perhaps post traumatic neuralgia in humans could be due to increased number of spinal cord cells responding to stimulation of the receptive field of the surviving nerve.

Animals↗

Effects of latrunculin A on immunological phagocytosis and macrophage spreading-associated changes in the F-actin/G-actin content of the cells.

Latrunculin A, a toxin from a Red Sea sponge, was shown to be a very potent inhibitor of immunological phagocytosis by normal and activated macrophages (obtained from mice injected i.p. with LPS), as well as by polymorphonuclear leukocytes. This toxin blocks the interiorization of the immune complexes but does not interfere with their binding to the phagocyte (recognition phase); activated macrophages were more susceptible to this inhibition than normal macrophages and polymorphonuclear leukocytes. The effect of the toxin on cellular spreading of macrophages was also studied using two kinds of substrate: glass, and glass covered with IgG immune complexes. Latrunculin A was able to impair the spreading of normal macrophages on glass covered with immune complexes, and could also completely reverse the spreading after it had occurred. Contrarily, in activated macrophages, this toxin could neither impede the spreading nor reverse it, a difference that might be a distinctive property of the activated state. We have also found that latrunculin A can reduce the percentage of F-actin in both normal and activated macrophages, the activated cells being more susceptible to this effect. Since latrunculin A is a blocking agent of actin polymerization in vitro, these results indicate that actin polymerization and assembly must be an essential component of the primary, active event of the engulfment phase of phagocytosis.

Actins↗

Hyaluronate coat formation and cell spreading in rat fibrosarcoma cells.

Hyaluronate-containing pericellular coats have been demonstrated around rat fibrosarcoma cells by exclusion of particles (fixed red blood cells). The cell coats normally form during spreading of the rat fibrosarcoma cells subsequent to subculturing. Monensin, a drug which disrupts the Golgi and which also inhibits hyaluronate synthesis in these cells, inhibits the regeneration of these coats after hyaluronidase or trypsin treatment but does not inhibit cell spreading. Cycloheximide, a drug which inhibits protein but not hyaluronate synthesis does not prevent coat regeneration but partially inhibits cell spreading. Thus by exploiting the opposing effects of cycloheximide and monensin on coat regeneration and cell spreading, we have been able to dissociate these two phenomena.

Animals↗

A Mr 72K cell surface concanavalin A binding glycoprotein is specifically involved in the spreading of chick embryo fibroblasts onto laminin substrate.

In the present study we have identified a 72-kDa cell surface concanavalin A binding glycoprotein (cbg 72) involved in the chick embryo fibroblast (CEF) adhesion onto laminin (LM) substrate. The cbg 72 was shown to interact specifically with immobilized laminin and to be resistant to Triton X-100 extraction when CEF were plated on laminin substrate but not on fibronectin (FN) substrate. This behavior suggested that cbg 72 could interact with cytoskeletal elements during cell spreading onto LM. This assumption is also in good agreement with the partitioning of cbg 72 in Triton X-114. Isolated cbg 72 specifically inhibited CEF spreading onto LM after their initial attachment, whereas cbg 72 did not impair the spreading of CEF onto FN. These data provide a molecular explanation to the inhibition of CEF spreading onto LM observed in the presence of the lectin concanavalin A (P. Codogno, M.-A. Doyennette-Moyne, J. Botti, and M. Aubery, 1988, J. Cell Physiol. 136, 463-470). Moreover, these results provide evidence for the role of a novel LM binding glycoprotein during the adhesion of mesenchymal derived cells. The relationship between cbg 72 and other known cell surface LM binding sites or receptors is discussed.

Animals↗

Substrate mechanics and cell spreading.

Cell spreading and cell locomotion arise from forces exerted by actin microfilaments upon the substratum. Using modified protein films at fluorocarbon oil--water interfaces as substrates, we have measured some minimal mechanical properties required of these films to support cell spreading forces in vitro. For murine 3T3-L1 fibroblasts, complete cell spreading was obtained when the films exceeded surface shear moduli and surface fracture points of 15 and 5 dyne/cm, respectively. The human WI-38 fibroblast required more robust films than did its transformed counterpart (WI-38/VA 13) in order to achieve equivalent spreading. These results are of significance in understanding the metastatic capabilities of cancer cells.

Actin Cytoskeleton↗

Observations on the role of ectodermal spreading in the early stages of lens placode invagination in the chick embryo.

The importance of differential epithelial spreading in the early stages of chick lens placode invagination in the chick has been demonstrated experimentally in two ways. Generalized swelling of the head caused by immersion in 50% ethanol and restricting the freedom of ectoderm in the eye region to spread by means of ligatures produce both precocious and exaggerated invagination. Inequality of spreading between the placode and surrounding ectoderm in normal development is caused by the adhesion of the former to the optic vesicle, while the ectoderm is free to spread and move over underlying tissues. Folds, i.e. invaginations, form at the boundary between the placode and its surroundings.

Animals↗

Effects of neurohormonal agents on jejunal contraction spread and transit in the fed dog.

The jejunal contraction patterns of dogs in response to intravenous infusion of neurotensin, somatostatin, secretin, and met-enkephalin were analyzed. The peptides were given after administration of a noncaloric viscous cellulose meal. A computer was used to determine the length of spread of contraction waves, their contraction force, the contraction frequency, and the motility index. Transit rates of luminal content were assessed videofluoroscopically. During saline infusion the cellulose meal was propelled aborally at a transit rate of 3.1 +/- 1.1 cm/s; the corresponding length of spread of contraction waves was 10.3 +/- 1.5 cm. All peptides decreased both the transit rate (0.45-1.81 cm/s) and the contraction spread (3.7-6.2 cm). Neurotensin increased the contraction force, but had no effect on contraction frequency and motility index. The other peptides reduced the motility index and the frequency and force of contractions. It was shown that the peptides influenced intestinal contraction patterns and the transit rate of luminal content. The length of spread of contraction waves was found to be most important in the regulation of transit.

Animals↗

Does bacillus Calmette-Guérin immunotherapy accelerate growth and cause metastatic spread of second primary malignancy?

In our study, 29 of 150 patients with bladder cancer also had other associated primary malignancies, 10 of which were manifested after intravesical treatment with bacillus Calmette-Guérin (BCG). Second primary malignancies developed in 5 of these patients within three months of the start of BCG therapy. All 5 showed acceleration of the second primary tumor, and distant metastatic lesions developed in 4. In the other 5 patients nonbladder primary malignancies developed eight months or more after intravesical BCG therapy started, but did not show acceleration or spread. Twenty patients with other primary malignancies that had developed months to years before intravesical therapy did not show acceleration or spread of those tumors. We have seen enough cases of patients who received intravesical BCG at the time of growth and spread of second primary malignancies to warrant concern. Animal and human studies of BCG use for treatment of malignancy indicate that the temporal relationship between the starting point of tumor development and the starting point of BCG treatment is crucial in determining whether BCG will eradicate or exacerbate the tumor. We have therefore instituted a change in our treatment until the question of whether or not BCG causes the appearance and spread of these second malignancies is answered.

Administration, Intravesical↗

Effects of prostaglandins on the spreading, adhesion and migration of mouse peritoneal macrophages.

The effects of prostaglandins on the in vitro properties of mouse peritoneal macrophages namely spreading, adhesion and migration were investigated. PGE1 and PGE2 inhibit the spreading and adhesion of complete Freund's Adjuvant induced peritoneal macrophages significantly at concentrations of 1 ng per ml and above whereas they enhance the migration of these cells at concentrations of 100 ng per ml and above. PGA2 and PGB2 are less potent as they inhibit spreading and adhesion only at a concentration of 1 microgram per ml. At his concentration PGB2 enhances migration whereas PG2 has no effect. PGF 2alpha has no effect on the spreading, adhesion and migration of macrophages in the concentration range of 0.1 ng to 1,000 ng per ml.

Animals↗