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334 records · Page 19Linked to original sources

Three-dimensional applicator system for carcinoma of the uterine cervix.

PURPOSE: Intracavitary dose prescription for cancer of the uterine cervix has been based on the use of plane orthogonal films. Computed tomography (CT) and magnetic resonance imaging can provide three-dimensional (3D) anatomic information with which more sophisticated treatment planning can be carried out. This work describes a new tandem and ovoids design that permits modern 3D dosimetry and has the same placement flexibility for the physician as the applicators currently being used. METHODS AND MATERIALS: The external shape of the Fletcher-Suit-Delclos (FSD) minicolpostat tandem and ovoids system has been used as a model to build a prototype of a new applicator. The prototype colpostats are constructed out of aluminum and steel. The tandems are made of aluminum. The Fletcher shields are eliminated. A new method of using tungsten for dose attenuation and shielding has been designed. Longitudinal alignment of the tungsten shields makes the new system possible. This applicator is CT-compatible. RESULTS: Dose calculations for the new design are compared to a commercial version of the FSD applicator. Both the aluminum prototype and a simple extension of the prototype to a plastic applicator system are considered. It is shown that the principal difference in dose is that the dose is reduced in the region inferior to the center of the ovoids. All configurations (plastic caps on or off) are equivalently shielded for the new device. In addition, an intermediate mini-ovoid configuration can be used clinically via the introduction of a D-shaped cap. The latter reduces the high dose to the vaginal mucosal surfaces. CONCLUSION: For a single ovoid, a comparison of dose with the FSD shows differences; however, the difference in dose is insignificant when the complete applicator, tandem, and ovoids are compared. With this new applicator, it is now possible to accumulate very accurate and detailed 3D dose-distribution data for the critical structures and other points of interest in the vicinity of the applicator. These data will permit future analysis of the correlation of dose and outcome for carcinoma of the cervix.

Brachytherapy↗

[Current status of CDDP analogs in gynecologic malignancies].

Among the cooperative studies of cisplatin (CDDP) analogs in gynecologic malignancies in Japan, a phase III study of CBDCA in ovarian cancer was completed in 1988, while phase II studies of 254-S and DWA2114R are ongoing at the present time. Phase II preliminary data in ovarian cancer revealed a response rate of 25-38%, almost equi-effective and less toxic to that of CDDP. Approximately 20% response rate was achieved in CDDP refractory cases, in particular, responders were observed in mucinous and mesonephroid cases considered CDDP resistant. A phase III study of CBDCA in ovarian cancer, with a comparative study of CAP regimen suggested that CBDCA-containing regimen has an advantage of unnecessity of hydration, in spite of no significant differences response and toxicity. In the cancer of the uterine cervix, approximately 20% response rate was achieved. Of interest is that 254-S yielded a response of 60%, and the result suggested that the agent may have broad antitumor spectrums, different to that of CDDP.

Adolescent↗

Cytopathology laboratory improvement programs of the College of American Pathologists: Laboratory Accreditation Program (CAP LAP) and Performance Improvement Program in Cervicovaginal Cytology (CAP PAP).

Major programs of the College of American Pathologists (CAP) are directed toward improvement of laboratory practices through peer review, interlaboratory comparison, education, and development of practice standards and guidelines. Two programs provided to cytopathology laboratories, the Laboratory Accreditation Program and the Interlaboratory Comparison Program in Cervicovaginal Cytology, are dedicated to these laboratory improvement principles. In 1996, each of these programs served over 2100 laboratories that provide cytopathology services. This paper reviews the peer development, structure, and administration of the Laboratory Accreditation Program and the Interlaboratory Comparison Program in Cervicovaginal Cytology, focusing on recent and ongoing initiatives to enhance their contribution to continued improvement of gynecologic cytopathology laboratory practices.

Accreditation↗

Immunolocalization of BMP-2/-4, FGF-4, and WNT10b in the developing mouse first lower molar.

Intercellular signaling controls all steps of odontogenesis. The purpose of this work was to immunolocalize in the developing mouse molar four molecules that play major roles during odontogenesis: BMP-2, -4, FGF-4, and WNT10b. BMP-2 and BMP-4 were detected in the epithelium and mesenchyme at the bud stage. Staining for BMP-2 markedly increased at the cap stage. The relative amount of BMP-4 strongly increased from E14 to E15. At E15, BMP-4 was detected in the internal part of the enamel knot where apoptosis was intense. In contrast to TGFbeta1, BMP-2 and -4 did not show accumulation at the epithelial-mesenchymal junction where the odontoblast started differentiation. When odontoblasts became functional, BMP-2 and BMP-4 were detected at the apical and basal poles of preameloblasts. BMP-2, which induces ameloblast differentiation in vitro, may also be involved physiologically. The decrease in FGF-4 from E14 to E15 supports a possible role for the growth factor in the control of mesenchymal cell proliferation. The relative amount of FGF-4 was maximal at E17. The subsequent decrease at E19 showed correlation with the withdrawal of odontoblasts and ameloblasts from the cell cycle. WNT10b might also stimulate cell proliferation. At E14-15, WNT10b was present in the mesenchyme and epithelium except for the enamel knot, where the mitotic activity was very low. At E19 there was a decreasing gradient of staining from the cervical loop where cells divide to the tip of the cusp in the inner dental epithelium where cells become postmitotic. The target cells for FGF-4 and WNT10b appeared different.

Ameloblasts↗

Cell-matrix interactions and cell-cell junctions during epithelial histo-morphogenesis in the developing mouse incisor.

The continuously growing rodent incisor develops mainly along its antero-posterior axis. The labio-lingual asymmetry which characterizes this tooth is initiated at the cap stage and increases further during the cap to bell transition (ED14 to ED16) when histogenesis of the enamel organ proceeds. Histology, transmission electron microscopy (TEM), and immunostaining were used to document the changes in the basement membrane (BM) as well as the modifications of epithelial cell-matrix and cell-cell interactions during this period. The expression of plakoglobin, desmoglein and E-cadherin at ED14 suggested that the main cell-cell junctional complexes were adherens junctions. The expression of desmoglein and TEM observations suggested a progressive antero-posterior stabilization of the enamel organ by means of desmosomes from ED14 to ED18. alpha6 integrin, BP 230 and laminin gamma2 chain were all expressed in the developing incisor but were not always co-distributed. Immunostaining and TEM suggested that only primitive type II hemidesmosomes were present. At ED14, cells of the enamel knot (EK) did not show any specific expression for antigens involved in cell-cell interaction. However, strong staining for the laminin gamma2 chain characterized the BM in contact with EK cells. The BM in the labial part of the cervical loop demonstrated ultrastructural changes: the presence of loops of the lamina densa in this region preceeded the differential expression of the integrin alpha6 subunit and that of the laminin gamma2 chain in the labial/lingual parts of the cervical loop. Apoptosis was transiently observed in the contiguous mesenchyme. This affected osteoblasts and also nerve cells close to the labial part of the cervical loop.

Animals↗

Incidence of complications with mini vaginal culpostats in carcinoma of the uterine cervix.

Between 1980 and 1987, 298 patients with carcinoma of the uterine cervix were treated at the University of Louisville Department of Radiation Oncology. Of these, 197 (66.1%) were treated for cure by radiotherapy alone: 36 by external beam alone and 161 by external beam and tandem and ovoid applications. The F.I.G.O. staging of the 161 patients was 82 (50.1%) Stage IB, 9 (5.6%) Stage IIA, 40 (24.9%) Stage IIB, and 30 (18.6%) Stage III. The usual treatment was whole pelvis irradiation followed by two intracavitary applications using the Fletcher Suit Applicators of tandem and ovoids in 79/161 patients (49%), a 3-M Mini Applicator (Fletcher Suit Delcos Applicator) in 52/161 patients (32.3%), and a 3-M Mini Applicator with Caps in 30/161 patients (18.6%). The incidence of grade 3-4 gastrointestinal or genitourinary complications as defined by the RTOG was 19.3% (31/161). Various treatment parameters were analyzed to define possible contributing factors. Grade 3-4 complications were seen in 7.6% (6/79) of patients treated with the standard ovoid Fletcher system, 26.9% (14/52) treated with the mini-ovoid system, and 36.6% (11/30) treated with the mini-ovoid system with caps (p = .0006). Although trends were noted, neither the vaginal surface dose (VSD) from the ovoids nor the addition of the external beam dose to the VSD (total vaginal surface dose = TVSD) were significant independent variables (p = 0.19 and = 0.133, respectively). The TVSD was significant when comparisons were made between different ovoid systems (p = 0.05 for less than 12,000 cGy and p = 0.004 for greater than 12,000 cGy). In this study, the 3-M mini applicator was associated with a significant increase in grade 3-4 complications as compared to the Standard Fletcher Suit Applicator.

Adult↗

[Side effects and anti-cancer effects following intraperitoneal (ip) administration of mitomycin C (MMC)].

Nineteen patients with gynecological cancers were initially treated intraperitoneally with MMC at a dose of 20 to 52 mg/body and then intravenously with CAP regimen. The following side effects were observed in patients intraperitoneally administered doses of MMC greater than 25 mg/m2; leucocytopenia 7/12, thrombocytopenia 5/12, liver damage 8/12, renal damage 2/12, ileus 3/12 and severe anorexia 2/12. Sixteen patients were evaluated for their prognoses more than 1 year after treatment. Seven of them are well with no sign of recurrence, but 9 suffered recurrence with or without peritonitis carcinomatosa (PC). The incidence of PC among these 9 cases was not linked with clinical staging, complete or incomplete resection or the dose of MMC administered, but rather with the respective histopathology; mesonephroid 2/2, metastatic 2/2, mucinous 1/1, serous 0/3, endometrial corpus 0/1. The results suggested that the former 3 kinds of cancer did not respond to i.p. infusion of MMC, whereas the latter 2 were sufficiently sensitive to MMC to prevent the occurrence of PC.

Female↗

Restoration of prehension with the double free muscle technique following complete avulsion of the brachial plexus. Indications and long-term results.

BACKGROUND: Recent interest in reconstruction of the upper limb following brachial plexus injuries has focused on the restoration of prehension following complete avulsion of the brachial plexus. METHODS: Double free muscle transfer was performed in patients who had complete avulsion of the brachial plexus. After initial exploration of the brachial plexus and (if possible) repair of the fifth cervical nerve root, the first free muscle, used to restore elbow flexion and finger extension, is transferred and reinnervated by the spinal accessory nerve. The second free muscle, transferred to restore finger flexion, is reinnervated by the fifth and sixth intercostal nerves. The motor branch of the triceps brachii is reinnervated by the third and fourth intercostal nerves to restore elbow extension. Hand sensibility is restored by suturing of the sensory rami of the intercostal nerves to the median nerve or the ulnar nerve component of the medial cord. Secondary reconstructive procedures, such as arthrodesis of the carpometacarpal joint of the thumb, shoulder arthrodesis, and tenolysis of the transferred muscle and the distal tendons, may be required to improve the functional outcome. RESULTS: The early results were evaluated in thirty-two patients who had had reconstruction with use of the double free muscle procedure. Twenty-six of these patients were followed for at least twenty-four months (mean duration, thirty-nine months) after the second free muscle transfer, and they were assessed with regard to the long-term outcome as well. Satisfactory (excellent or good) elbow flexion was restored in twenty-five (96 percent) of the twenty-six patients and satisfactory prehension (more than 30 degrees of total active motion of the fingers), in seventeen (65 percent). Fourteen patients (54 percent) could position the hand in space, negating simultaneous flexion of the elbow, while moving the fingers at least 30 degrees and could use the reconstructed hand for activities requiring the use of two hands, such as holding a bottle while opening a cap and lifting a heavy object. The results were analyzed to identify factors affecting the outcome. CONCLUSIONS: The double free muscle procedure can provide reliable and useful prehensile function for patients with complete avulsion of the brachial plexus.

Accessory Nerve↗

Maternal beta-catenin establishes a 'dorsal signal' in early Xenopus embryos.

In previous work, we demonstrated that maternally encoded beta-catenin, the vertebrate homolog of armadillo, is required for formation of dorsal axial structures in early Xenopus embryos (Heasman, J., Crawford, A., Goldstone, K., Garner-Hamrick, P., Gumbiner, B., Kintner, C., Yoshida-Noro, C. and Wylie, C. (1994). Cell 79, 791-803). Here we investigated, firstly, the role(s) of beta-catenin in spatial terms, in different regions of the embryo, by injecting beta-catenin mRNA into individual blastomeres of beta-catenin-depleted embryos at the 32 cell stage. The results indicate that beta-catenin can rescue the dorsal axial structures in a non-cell-autonomous way and without changing the fates of the injected cells. This suggests that cells overexpressing beta-catenin send a 'dorsal signal' to other cells. This was confirmed by showing that beta-catenin overexpressing animal caps did not cause wild-type caps to form mesoderm, but did cause isolated beta-catenin-deficient marginal zones to form dorsal mesoderm. Furthermore beta-catenin-deficient vegetal masses treated with overexpressing caps regained their ability to act as Nieuwkoop Centers. Secondly, we studied the temporal activity of beta-catenin. We showed that zygotic transcription of beta-catenin starts after the midblastula transition (MBT), but does not rescue dorsal axial structures. We further demonstrated that the vegetal mass does not release a dorsal signal until after the onset of transcription, at the midblastula stage, suggesting that maternal beta-catenin protein is required at or before this time. Thirdly we investigated where, in relationship to other gene products known to be active in axis formation, beta-catenin is placed. We find that BVg1, bFGF, tBR (the truncated form of BMP2/4R), siamois and noggin activities are all downstream of beta-catenin, as shown by the fact that injection of their mRNAs rescues the effect of depleting maternally encoded beta-catenin. Interference with the action of glycogen synthase kinase (GSK), a vertebrate homolog of the Drosophila gene product, zeste white 3 kinase, does not rescue the effect, suggesting that it is upstream.

Animals↗

Early developmental expression and experimental axis determination by the chicken Vg1 gene.

BACKGROUND: Genes of the transforming growth factor beta (TGF beta) superfamily have been implicated in the earliest steps of developmental patterning in vertebrates. In Xenopus, the Vg1 gene is a candidate for the initiator of axis formation: its RNA and protein are broadly but appropriately localized at the start of development, and processed Vg1 protein is a powerful inducer of organized axial tissue in blastular animal caps in vitro and when locally produced in vivo after injection of Vg1 mRNA into blastomeres. Site-specific proteolytic processing occurs ubiquitously for most TGF beta members, producing the active peptide ligand, but is tightly restricted, by unknown mechanisms, for endogenous Vg protein in Xenopus and zebrafish embryos. This restriction may be involved in the spatial localization of activity required for an organizing role. RESULTS: We have characterized an amniote (chick) orthologue of Vg1, cVg1, and examined its developmental expression. The early expression of cVg1 includes a phase broadly related to the known time and site of axis (primitive streak) initiation; the initial transcription of cVg1 is centred in the posterior marginal zone (PMZ), a region of the blastoderm known to contain the axial organizing activity at this stage. We also observed later neural and paraxial mesodermal expression of cVg1, which has not been described previously for Vg homologues in other vertebrates. We have grafted transfected COS cells, producing processed cVg1 protein, to peripheral positions around the chick early blastoderm. Such grafts initiate formation of morphologically complete primitive streaks, simulating the properties of grafts from the PMZ. CONCLUSIONS: In vertebrate development, Vg genes may be required for an evolutionarily conserved early step in positioning or induction of the axis.

Amino Acid Sequence↗