[Resection and free flap repair of recurrent maxillofacial and paranasal sinus skull base malignant tumor: report of 9 cases].

Objective: To investigate the treatment method and effect of surgical resection and free flap repair of recurrent malignant tumors of maxillofacial paranasal sinus and skull base. Methods: The clinical data of 9 patients with recurrent maxillofacial paranasal sinus and skull base malignant tumors who underwent surgical resection and free flap repair in the Department of Otorhinolaryngology Head and Neck Surgery of Shandong Provincial Hospital from August 2009 to May 2019 were analyzed retrospectively, including 5 males and 4 females, aged 32-69 years. There were 4 cases of squamous cell carcinoma, 3 cases of adenoid cystic carcinoma, 1 case of myoepithelial carcinoma and 1 case of malignant fibrous histiocytoma. All patients were repaired with anterolateral femoral flap. The treatment process and postoperative effect were analyzed by descriptive statistics. Results: All patients were followed up from 16 months to 6 years. There were 6 cases of recurrence after operation, including 1 case of local recurrence and 5 cases of skull base and craniocerebral recurrence. The median tumor free survival time of recurrent patients was 35 months. Conclusion: Surgical resection and free flap repair can effectively prolong the life of patients with recurrent maxillofacial paranasal sinus and skull base malignant tumors.

[Granulomatosis with polyangiitis with nasal symptoms as the first clinical manifestation: clinical analysis of 18 cases].

Objective: To analyze and summarize the diagnosis, treatment and prognosis of granulomatosis with polyangiitis (GPA) with nasal symptoms as the first clinical manifestation. Methods: The data of 18 patients of GPA with nasal mucosal symptoms as the first clinical manifestation from the Department of Otorhinolaryngology Head and Neck Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University between 2005 and 2019 was collected, including 8 males and 10 females, aged from 5 to 68 years. Nasal endoscopy, imaging examination, laboratory examination, immunological and histopathological examination of nasal mucosa were completed. All patients were treated with glucocorticoid combined with cyclophosphamide and were followed up for 2 to 15 years. Descriptive statistical method was used for analysis. Results: All the 18 patients had the nasal mucosal symptoms as the first clinical manifestation, including nasal obstruction, running nose and epistaxis. Nasal endoscopy showed swelling, erosion, scab and bleeding of nasal mucosa, and 6 cases had nasal septal perforation. Nasal sinus CT scan showed high density shadow of sinus, as well as hyperostosis and osteosclerosis. CT imaging features of pulmonary showed nodular lesion or patchy infiltration in 12 patients and cavitation was found in 6 cases. Laboratory results showed that 13 cases were positive for anti-neutrophil cytoplasmic antibodies (ANCA), and 5 cases were negative. During follow-up period, thirteen patients were symptomatic controlled and survived; two patients died of disease progression; one patient gave up treatment and died; two patients were lost to follow-up. Conclusions: Nasal symptoms are the first clinical manifestation of GPA. Early diagnosis and early treatment with glucocorticoid combined with cyclophosphamide can effectively improve the survival rate.

[Skull base aneurysms: a retrospective review of fifteen cases focusing on the involvement of internal carotid artery].

Objective: To explore the diagnosis and clinical features of internal carotid artery aneurysm in the skull base. Methods: The data of 15 patients with internal carotid aneurysms in the skull base diagnosed and treated by digital subtraction angiography (DSA) or CT angiography (CTA) in the Provincial Hospital Affiliated to Shandong First Medical University from 1995 to 2017 were collected and analyzed. Among the 15 patients, 12 were males, and 3 were females, aging from 17 to 67 years old, with a median age of 44 years. Thirteen patients were diagnosed by DSA; the other two patients were diagnosed by CTA. Thirteen patients were diagnosed with pseudoaneurysm with the first symptom of epistaxis, in which eight patients underwent head trauma and 5 underwent radiotherapy of skull base tumor. The other two patients were diagnosed with true aneurysm presented headache and cranial nerve disorder. All patients were followed up for 2 to 12 years after treatment to see whether they were cured and survived. Results: Among the eight patients with a history of trauma, five patients were cured by embolization, two patients without embolization died of massive epistaxis, one patient died of progressive cerebral infarction after embolization. Among the five patients with radiotherapy of skull base tumor, one patient died of cerebral infarction after embolization, two patients died out of the hospital due to the recurrence of the primary tumor and intracranial invasion, one patient recovered well after embolization and surgical operation, one patient gave up treatment and died of massive hemorrhage out of hospital. In the other two patients with symptom of headache, one received embolization treatment outside the hospital after receiving mistake operation, and another one gave up treatment and died due to personal reasons. In total, four patients died in hospital, four died out of the hospital, and seven patients survived. Conclusions: Internal carotid artery aneurysm is a high-risk disease of anterior and middle skull base. For patients with epistaxis with a history of trauma and radiotherapy or patients with headaches and cranial nerve disorders, the possibility of the internal carotid artery aneurysm should be considered, in which DSA or CTA examination is essentially required for ensured diagnosis and disease evaluation.. The correct diagnosis and treatment by the otolaryngologist are crucial to the prognosis of the patient.

[Reconstruction of orbital floor defect with preserved orbital contents after advanced maxillary sinus cancer resection].

Objective: To analyze the method and effect of reconstruction of the orbital floor defect with preserved orbital contents after advanced maxillary sinus cancer resection. Methods: Thirty-three patients of T3/T4 stage maxillary sinus cancer with orbital invasion who were treated in Shandong Provincial Hospital from January 2010 to October 2016 were retrospectively analyzed, including 20 males and 13 females, aged from 12 to 80 years old. Patients were treated with appropriate surgical methods according to their clinical manifestation, imaging finding, invasion range, preoperative and intraoperative pathology. Surgical approaches such as maxillectomy, expanded maxillectomy and superstructure maxillectomy were used for patients with Medpor orbit floor repairment. Patients were followed up regularly after surgery, and the surgical efficacy was discussed by descriptive statistical method. Results: Of those 33 cases, 19 were squamous cell carcinoma, 8 were adenoid cystic carcinoma, 5 were inverted papilloma malignant transformation, and 1 was myoepithelial carcinoma in our study. After tumor resection and orbital floor repair, the orbital contents and eyeball function of all patients remained intact. During follow-up time ranged from 3 to 8 years, a total of 6 patients relapsed at 3 years and died of ineffective treatment. The survival rate was 81.8% (27/33). Conclusion: Tumor resection and Medpor orbital floor repair in maxillary sinus cancer patients with orbital invasion can preserve the function of the eyeball well, greatly improve the quality of patient's life.

[Clinical analyses of the diagnosis and treatment of invasive fungal rhinosinusitis: report of 14 cases].

OBJECTIVE: Through the retrospective analysis of the clinical data in 14 cases of invasive fungal rhinosinusitis (IFRS), the clinical characteristics, diagnosis and treatment of this disease were evaluated. METHODS: Fourteen clinically confirmed cases of IFRS since January 2008 to October 2015 were evaluated.collected, the clinical features, diagnosis, treatment and prognosis were analyzed to obtain a more comprehensive understanding for clinical reference. Fourteen patients were confirmed by pathological examination as IFRS, including 9 cases of aspergillus, 4 cases of mucor, and 1 case of rhinocerebral zygomycosis; including 5 cases of acute IFRS, 9 cases of chronic IFRS. All patients were treated with endoscopic surgery and intravenous antifungal therapy. RESULTS: Nine cases of chronic IFRS (including 1 case of mucor, 7 cases of aspergillus and 1 case of rhinocerebral zygomycosis) were cured, but the vision loss, diplopia or blindness, hard palate perforation remained. Five cases of acute IFRS included 3 cases of mucor and 2 cases of aspergillus. Among the 3 cases of mucor, 2 cases were died and 1 case was cured. Among the 2 cases of aspergillus, 1 patient was cured and the other patient died of electrolyte disorder after discharge from hospital. CONCLUSIONS: Patients with IFRS usually have diabetes. After the active surgical cleaning of lesion tissue and the systematic antifungal treatment with adequate dosage, these patients would have a better result. IFRS caused by mucor is ofen dangerous.

Sequence variants in the bovine nucleophosmin 1 gene, their linkage and their associations with body weight in native cattle breeds in China.

The nucleophosmin (nucleolar phosphoprotein B23, numatrin) gene (NPM1, previously known as nucleophosmin/nucleoplasmin family, member 1) encodes a multifunctional nucleolar phosphoprotein that plays a crucial role in cell growth and homeostasis. Seven sequence variants (SVs) were identified in the coding region of bovine NPM1, five of which were in complete linkage disequilibrium. Eight different haplotypes were identified, of which two major haplotypes have a frequency of 23.2% and 20.4%. Three SVs were significantly associated with body weight in the Nanyang population as analysed at different ages. No significant association was detected between 18 combined genotypes and body weight at five different ages. Our results suggest that some polymorphisms in NPM1 are associated with body weight at some ages and may be used as candidates for marker-assisted selection and management in beef cattle breeding programmes.

Novel 12-bp deletion in the coding region of the bovine NPM1 gene affects growth traits.

The nucleophosmin 1 gene (NPM1) encodes a multifunctional nucleolar phosphoprotein that plays a crucial role in the control of various aspects of cell growth and homeostasis. In this study, the coding region of the NPM1 gene was screened in 1035 individuals of 4 Chinese cattle breeds by DNA sequencing and polyacrylamide gel electrophoresis. A novel 12-bp deletion mutation was identified in the coding region of the NPM1 gene. The PCR products of primer NPM1-P2 exhibited 3 genotypes and 2 alleles: 178 bp (denoted as W) and 166 bp (denoted as D). Genotype DD and allele D were predominant in the studied populations. Association analysis with growth traits in the Nanyang breed (N = 265) showed that the animals with genotype DD had significantly greater birth weight, body weight, body length, and heart girth than those with genotype WD (P < 0.01 or P < 0.05) at birth and after 6 months and 12 months, but not at 18 and 24 months of age. Results of this study suggest that the NPM1 gene is a candidate gene for growth traits in cattle.

Torque properties of a rat oesophagus for physiological and diabetic conditions.

In this paper the torque of an oesophagus is studied for physiological and diabetic conditions. Since the function of the oesophagus is mainly mechanical, this work is focused on providing quantitative measurement of the passive biomechanical properties of the oesophagus torque. The oesophagus was treated as a membrane when calculating the stress and strain. The torque versus twist-angle relation was approximated to be linear at a specified pressure and longitudinal stretch ratio. Thus, the shear modulus can be computed by the torque, twist angle and polar moment of inertia in this state. The shear modulus varies greatly with the changing inflation pressure and longitudinal stretch ratio. When the longitudinal stretch ratio or transmural pressure is constant, the shear modulus is increased after 28 days of diabetes.

[Effect of topical dexamethasone treatment on antigen-presenting cells in murine corneas]. / Topische Dexamethason-Therapie. Einfluss auf antigenpräsentierende Zellen in der Hornhaut der Maus.

OBJECTIVE: To determine the influence of dexamethasone treatment on APCs and the time of graft survival of MHC-disparate grafts. METHODS: Flatmounts of the ocular surface prepared with EDTA and tangential frozen sections of the remaining corneal stroma from untreated eyes of normal mice (n=6) and from eyes treated for 7 days with dexamethasone ( n=6) were immunohistologically examined for content of F4/80+ and MHC II+ cells.Furthermore, corneas of C(3)H mice without and with 7-day dexamethasone eye drop treatment (n=8) were grafted into BALB/c mice receiving the same treatment. RESULTS: The number of positive cells within the epithelial flatmounts showed a dramatic reduction in the dexamethasone-pretreated group (p<0.01 compared to the untreated control group). The number of positive cells in the corneal stroma remained unchanged. The grafts of untreated control mice survived 16+/-4 days, the treated grafts 16+/-3 days. CONCLUSIONS: Most investigators assume that normal murine corneas contain no APCs such as macrophages and Langerhans cells. For the first time we were able to detect APCs in flatmounts of the ocular surface and frozen sections of corneal stroma. Our investigations show that, in contrast to the ocular surface, the number of F4/80+ cells in the corneal stroma is not influenced by dexamethasone treatment. Transplantation of corneas containing donor-derived APCs promotes acute rejection (direct pathway of allorecognition).Thus,dexamethasone treatment did not prolong the time of allograft survival.

[Immunomodulation after keratoplasty by CTL4-Ig and anti-CD154 antibodies]. / Immunmodulation nach Keratoplastik durch CTLA4-Ig und anti-CD154-Antikörper.

BACKGROUND: The immunoreaction after corneal transplantation is caused by the T cell receptor interacting with the major histocompatibility complex (MHC) receptor of the antigen-presenting cell. The signal is amplified by the CD4 receptor and the costimulatory signal interactions of CD28-B7 and CD40-CD154. We investigated the influence of costimulatory signal blocking on corneal transplant survival in mice. METHODS: Seven groups of 6 BALB/c mice received an orthotopic corneal transplant from C3H mice differing in minor and major MHC and were postoperatively treated as follows: (1) 80 micrograms of CTLA4 fusion protein intraperitoneally (i.p.) for 6 days; (2) 50 microliters of PBS i.p. for 6 days; (3) 1 mg of Solu-Decortin H i.p. for 5 days + dexamethasone AT 0.1% for 35 days; (4) therapy (3) + 50 micrograms of CTLA4 fusion protein i.p. for 6 days; (5) CTLA4-Ig as in (1) + 15 micrograms of anti-CD154 subconjunctivally (s.c.) on days 0, 2, 4, 6, and 8; (6) CTLA4-Ig as in (1) + 25 micrograms of anti-CD154 s.c. for 9 days; and (7) 25 microliters of PBS s.c. for 9 days. RESULTS: All animals had an immunoreaction on the following days: (1) day 18 +/- 3.1; (2) day 13.6 +/- 1.6; (3) day 48 +/- 6.6; (4) day 65 +/- 41; (5) day 23.5 +/- 8.5; (6) day 16.2 +/- 3.6; (7) day 13.8 +/- 2.7. CONCLUSION: The significant prolongation of transplant survival achieved by corticosteroids alone (P < 0.001) is again significantly increased by combining them with CTLA4-Ig (P < 0.001). Specific immunotherapy combined with nonspecific steroid therapy may also improve clinical corneal transplantation results. Compared to the two control groups, CTLA4-Ig and anti-CD154 only influenced transplant survival at a low dosage (P < 0.001).

Contribution of lymphatic drainage system in corneal allograft rejection in mice.

PURPOSE: To modulate aqueous outflow via the uveoscleral pathway and to determine its influence on corneal graft survival in mice. METHODS: BALB/c mice received corneal transplants from C3H mice and were placed randomly in three treatment groups: saline, pilocarpine or latanoprost. Three further groups received adjuvant systemic and topical corticosteroids. The kinetics of infiltrating lymphocytes, neutrophils and macrophages in the transplants was investigated in an additional 96 animals. Cytokine expression in the submandibular lymph nodes and spleen was investigated using in-situ hybridization and RNAse protection assay. Tracer experiments were conducted using 99mTC colloidal albumin Nanocoll; count rates were determined in the submandibular lymph nodes, spleen and blood following both subconjunctival and intracameral injection. RESULTS: Neither pilocarpine nor latanoprost had any influence on aqueous outflow or allograft survival in mice. Neutrophils and macrophages dominated the infiltrating cells 11 days postoperative in both treated and untreated grafts. On postoperative day 13, a greater increase in lymphocytes than in other cell groups was observed in allogeneic grafts. Following allogeneic transplantation, 1% of lymphocytes in ipsilateral submandibular lymph nodes were positive for IFN-gamma. Tracer studies revealed a 16% aqueous outflow via the uveoscleral routes following intracameral injection of Nanocoll; this was increased by 97% with subconjunctival injection. CONCLUSION: Our data confirm the existence of functional lymphatic drainage via the uveoscleral pathway and conjunctiva in the mouse. Cells within the ipsilateral submandibular lymph node respond to stimuli upstream. This reaction could potentially be manipulated to improve graft survival.

Ballistic transfer of minimalistic immunologically defined expression constructs for IL4 and CTLA4 into the corneal epithelium in mice after orthotopic corneal allograft transplantation.

BACKGROUND: Experiments were performed to determine whether corneal epithelium transfected with minimalistic immunologically defined expression constructs for the extracellular fragment of CTLA4 and for interleukin-4 (IL-4) or interleukin-10 (IL-10) is able to modulate an allospecific immune response after orthotopic corneal grafting in mice. METHODS: Six groups of BALB/c (H-2d) mice received a C3H (H-2k) corneal graft and dexamethasone eye drops until day 11. Five groups of BALB/c mice had gold particles delivered into the corneal epithelium by Gene Gun on day 10 after transplantation. In four groups, minimalistic immunologically defined gene expression (MIDGE) vectors were delivered into the corneal epithelium by ballistic transfer. The levels of expressed IL-4 and IL-10 were determined by an enzyme-linked immunosorbent assay (ELISA) in shock-frozen homogenized corneas. The expression kinetics of Gene-Gun-transfected corneas were determined by measuring luciferase in lysed whole corneas at different time intervals. RESULTS: Luciferase expression was detectable during the first 5 days following transfection. ELISA was used to determine IL-4 and IL-10 expression in corneal tissue 36 h after transfection. Ballistic IL-4 and CTLA4 gene transfer significantly prolonged corneal graft survival in comparison with the gold-treated control group and the IL-10-treated group. CONCLUSION: The beneficial effect of IL-4 and CTLA4, but not IL-10 gene transfer into the corneal epithelium by MIDGE vectors was demonstrated for the first time in corneal transplantation.

A comparison of the Chinese 1992 and fifth-edition International Union Against Cancer staging systems for staging nasopharyngeal carcinoma.

BACKGROUND: The Chinese 1992 staging system for nasopharyngeal carcinoma (NPC) has been widely adopted in mainland China since 1992. The fifth edition of the International Union Against Cancer (UICC) TNM classification defines new rules for classifying NPC. The current study compares the two in predicting NPC prognosis. METHODS: Four hundred eleven NPC patients, most of whom had disease of undifferentiated histologic type and were treated in a constant fashion and with definitive intent with radiation therapy alone, entered this comparative study. The patients were restaged according to the rules of the fifth edition of the UICC staging manual and the Chinese 1992 staging system. RESULTS: In the opinion of the authors, the predictive power of the Chinese 1992 T classification was superior. Conversely, the authors felt that the UICC N classification was more reasonable. The patients were categorized more evenly by the UICC stages than by the Chinese 1992 stages. The 5-year disease specific survival rates for patients in corresponding stages of both systems were almost identical despite differences in the criteria defining T and N classifications. Statistical analysis showed that the agreement rate was 72%. There were some agreement and correlation between the two staging systems. CONCLUSIONS: Both systems are essentially similar. Each system appears to have some subtleties that could improve the outcome prediction of the other system if the two were somehow combined. However, it appeared to the authors that the UICC system was slightly better.

The effect of corticosteroid and cyclosporin A on murine corneal allograft rejection.

BACKGROUND: The immunomodulatory T-helper type 1 (Th1) cytokine interferon-gamma (IFN-gamma) was measured in serum and cornea to ascertain its general contribution to corneal graft rejection and to establish a rational basis for the decision for or against systemic therapy. METHODS: Eight groups of differently treated BALB/c (H-2d) mice received a C3H (H-2 k) corneal graft. There was one saline-treated control group and two groups that received intramuscular cyclosporin A (CsA) for 14 or 40. Three groups received systemic or topical, systemic plus topical corticosteroid treatment, which was combined with CsA in two further groups. To measure the IFN-gamma level by enzyme-linked immunosorbent assay (ELISA), blood was taken by heart puncture and corneae were excised at the limbus. RESULTS: Five days of systemic corticosteroid and 14 days of CsA had no significant effect on graft survival. A 40-day CsA treatment and a 40-day combined corticosteroid treatment significantly prolonged graft survival. An 80-day topical corticosteroid treatment produced additional prolongation. IFN-gamma could not be detected (limit of detection 25 pg/ml) in any of the serum samples, while significantly increased amounts of IFN-gamma were detected in the supernatants of the corneal tissue 13 or 14 days after allogeneic but not syngeneic corneal graft, corresponding to 9.5 pg, 5.1 pg and 1.8 pg per cornea. CONCLUSION: The detection of Th1 cytokines in the cornea but not the serum of mice at the time of allograft rejection is in accordance with the finding of long-lasting dose-dependent immunosuppression of topical steroids and the inefficacy of short-term systemic CsA and corticosteroids.

Immunohistology of corneal wound healing after photorefractive keratectomy and laser in situ keratomileusis. wachtlin@ukbf.fu-berlin.de.

PURPOSE: The aim of the study was to compare corneal wound healing after photorefractive keratectomy (PRK) and laser in situ keratomileusis (LASIK) using conventional, immuno- and enzymohistologic methods. METHODS: Sixteen white Russian rabbits in each group underwent PRK or LASIK. Keratocyte density was recorded from 1 week to 6 months post-operatively on conventional histological sections. Immunohistologic cellular fibronectin and tenascin were used as markers of early epithelial and stromal wound healing in the cornea. The cell damage was demonstrated enzymohistologically using alkaline phosphatase. RESULTS: The reaction was similar in quality with both methods and occurred at sites of simultaneous epithelial and stromal injury. Mild scarring was found around the edge of the flap after LASIK; PRK-treated corneas developed a central subepithelial haze and scarring. A hypocellular region was found in the anterior part of the ablation zone shortly after PRK. Fibroblast migration later led to hypercellularity and subsequent clinical haze formation. After LASIK this reaction was limited to the peripheral entry point of the microkeratome blade around the edge of the corneal flap, where cellular fibronectin and tenascin reactions were positive. An acellular zone was found anterior to the interface after LASIK. The keratocyte damage visualized by alkaline phosphatase was more extensive after PRK than after LASIK. CONCLUSION: The stromal reaction to surgery was more extensive after PRK than after LASIK. A cytokine-mediated interaction between the epithelium and stroma was suggested as the cause of keratocyte cell migration and scar formation.

Prolongation of corneal allograft survival by an interleukin-2-immunoglobulin fusion protein in mice.

BACKGROUND: Interleukin 2 (IL2) production by activated T-helper cells leads to activation and proliferation of cytotoxic T cells. Recently, an IL2-IgG fusion protein was found to suppress cell-mediated and humoral immune responses in mice. METHODS: We used the genetically engineered murine IL2-IgG2b fusion protein in a fully MHC-mismatched mouse keratoplasty model. The DTH reaction against sheep red blood cells was investigated as a measure of IL2-IgG2b-mediated immunosuppression. The animals were divided into three control groups (n > or = 6) [no treatment, subconjunctival (SQ) treatment with saline or mouse serum], two IL2 SQ-treated groups (14 micrograms or 140 micrograms), and four IL2-IgG2b-treated groups (14 micrograms, 140 micrograms or 280 micrograms SQ or 280 micrograms i.p.). RESULTS: Administration of 20 micrograms of IL2-IgG2b twice daily from the time of immunization until the time of challenge resulted in almost complete prevention of footpad swelling. The 140 micrograms SQ application of IL2 (allograft reaction on day 20.5 +/- 4.04) and the 280 micrograms SQ (day 19.2 +/- 2.48) or i.p. (day 19.7 +/- 1.5) application of IL2-IgG2b fusion protein significantly prolonged the corneal graft survival in comparison to the untreated group (day 13.4 +/- 1.35) (P < 0.01) or saline control group (P < 0.01) and the mouse-serum-treated group (day 14.7 +/- 3.5) (P < 0.05). CONCLUSION: Our results indicate that, at a total dose of 280 micrograms, the fusion protein IL2-IgG2b causes no detectable side effects and very effectively suppresses the immune response of the corneal allograft in mice. This fusion protein could prove useful in the treatment of allograft rejections and autoimmune diseases.

Inhibition of corneal allograft reaction by CTLA4-Ig.

BACKGROUND: Activation of T cells requires both the interaction of T-cell receptor with major histocompatibility complex on the antigen-presenting cell and costimulatory signals, for instance the B7 antigens expressed on antigen-presenting cells and the CD28 molecule expressed on T cells. A recombinant fusion protein, CTLA4-Ig, has been produced that contains the extracellular domain of human CTLA4 fused to IgG1 constant region and that binds the B7 molecule with high affinity. Blocking the CD28/B7 interaction with CTLA4-Ig inhibits T cell activation in vitro and in vivo. METHODS: We used CTLA4-Ig in a fully MHC-mismatched mouse keratoplasty model. The animals were divided into four groups: (1) no treatment, (2) intraperitoneal treatment with 130 micrograms CTLA4-Ig, (3) intraperitoneal treatment with 300 micrograms CTLA4-Ig, (4) subconjunctival treatment with 290 micrograms CTLA4-Ig. RESULTS: The allograft reaction occurred in untreated animals between days 12 and 16 (mean 13.5). While topical application of CTLA4-Ig seemed to shorten the graft survival (mean 11.6 days) and systemic application of 130 micrograms had no influence (mean 14.0), only intraperitoneal injection of 300 micrograms of CTLA4-Ig prolonged the survival of allografts (mean > 20 days) (P < 0.01). CONCLUSION: CTLA4-Ig prolonged significantly the survival of corneal allografts in a fully MHC-mismatched mouse keratoplasty model, but the small antigen load of the corneal transplant and the anterior chamber-associated immune deviation (ACAID) may have a disadvantage to induce tolerance in this model of CTLA4-Ig therapy.

Orthotopic corneal transplantation in the mouse--a new surgical technique with minimal endothelial cell loss.

BACKGROUND: The murine model of orthotopic perforating keratoplasty is important for studying the allograft reaction, but the small dimensions cause technical difficulties. METHODS: The anterior chamber of the eye of the BALB/c mouse was measured with the confocal microscope and with histological methods. Ten C3H mouse donor corneas each were separated by the conventional technique and by the newly developed "underwater" technique, where the opened donor eye did not lose its shape under water. The corneal endothelium was stained with trypan blue and alizarin red S. Ten BALB/ c (H-2d) mice received a corneal graft taken from a C3H (H-2k) mouse by the underwater technique. RESULTS: The 3.7-mm eye of the BALB/c mouse has a corneal diameter of 3.5 mm. The cornea has a central thickness of 170 microns, the epithelium comprising 30% and the stroma 70%. While none of the corneas separated by the new "underwater" technique evidenced endothelial damage, a 28 +/- 17.0% defect of the endothelial surface was found with the conventional technique. All transplanted corneas were clear when the lids were opened on the 2 postoperative day and clouded between the 7th and 30th days (mean 16.5 days) due to an allograft reaction. CONCLUSION: The newly developed "underwater" technique is superior to the conventional technique, since floating of the very thin donor cornea during the separation procedure prevents endothelial defects by guarding against folds. By enabling reliable keratoplasty in the mouse, this technique facilitates studies on the experimental allograft reaction.

Radiation therapy of nasopharyngeal carcinoma: prognostic factors based on a 10-year follow-up of 1302 patients.

One thousand three hundred and two patients with carcinoma of the nasopharynx were initially treated with radiation therapy at this hospital in 1974. The overall 1-, 3-, 5-, and 10-year survival rates were 89.86%, 60.60%, 47%, and 33.03% respectively. At the end of the radiotherapeutic course the residual lesion rate was 10.52% in the nasopharynx 17.27% in cervical lymphnode. In about one-half of the cases with residual lesions, the masses disappeared without further treatment. Prognosis was not improved in the group with supplemental doses. The recurrence rates of the primary nasopharyngeal and metastatic cervical lesion were 18.43%, and 16.12% respectively within 10 years after initial treatment. The 10-year survival rate of the patients with a second course of radiotherapy was 15.04%, higher than of those not retreated (4.9%). Data of this group also reveal that the present pathological classification cannot reflect the degree of prognosis. Increase dosage or combination with chemotherapy did not improve the prognosis. Radiation encephalomyetic damage is discussed.