A novel method for gene delivery and expression in esophageal epithelium with fibrin glues containing replication-deficient adenovirus vector.

BACKGROUND: Gene transfer to the esophageal epithelium holds the potential for the therapy of malignant as well as premalignant lesions in the upper gastrointestinal tract. Replication-deficient recombinant adenoviruses represent an efficient means of introducing genes in vivo into cells in a variety of organs. The majority of in vivo studies utilize direct submucosal injection for delivery of the viral vectors into the locoregional area of the gut; transferring genes into epithelial cells, however, is difficult because viruses are retained in the subepithelial space. To establish the efficient method for gene transfer into the epithelial cells, we have developed a multiluminal spray catheter that can be passed through the accessory channel of an endoscope, and we have evaluated the feasibility of fibrin glues as a vehicle of recombinant adenoviruses in a porcine model. METHODS: The fibrinogen solution and the thrombion solution containing an E1/E3 deleted recombinant adenovirus expressing the bacterial lacZ gene (Ad-lacZ) were endoscopically sprayed on the porcine esophagus through the catheter attached to the dual-barrel syringe. Twenty-four hours after gene delivery, beta-galactosidase activity of the esophagus was determined under the microscope following X-gal staining. RESULTS: The fibrin glue could be locally sprayed on the porcine esophagus by using the multichannel catheter through the endoscope. Attachment of the fibrin glue comtining Ad-lacZ caused strong beta-galactosidase staining on epithelial cells in the mucosal surface, but not in the basal cell layer. CONCLUSION: Endoscopic local delivery of recombinant adenoviruses in aerosolized fibrin glues through a multiluminal catheter could provide an optimal technique for gene transfer into epithelial cells in the mucosal surfece, which may have important implications for the treatment of human esophageal premalignant diseases.

Consideration of operative procedures for zygomatic reduction in Orientals: based on a consecutive series of 28 clinical cases.

Operative procedures for reduction malar bone plasty were considered in our consecutive series of 28 Japanese cases. The patients consisted of 7 males and 21 females whose ages ranged from 21 to 57 years. The operative procedures used were either shaving the protruded zygomatic body and arch with chisels by means of an intraoral approach and/or an extraoral sideburn-lateral canthal approach or, alternatively, mobilizing the protruded zygoma en bloc medioposteriorly into reduction of the prominent zygoma by a coronal approach. In principle, the noncoronal approach was indicated for males and young females, and the coronal approach, conducted in association with forehead lifting with or without canthopexy, was indicated for females over age 40. These procedures have individual merits and demerits. In some cases, associated surgery was performed concomitantly according to the facial balance or facial rejuvenization. We believe that the optimal operative approach and operative procedure should be considered in accordance with the patient's sex, age, wishes, and/or cultural background.

Cranioplasty with neovascularized autogenous calvarial bone.

We have presented two cases of cranioplasty with neovascularized autogenous calvarial bone. A surgical procedure applying the principle of flap prefabrication has been applied to the preservation of autogenous calvarial bone obtained during external cranial decompression. The rectus abdominis muscle flap was elevated. A subcutaneous pocket was prepared for preservation of calvarial bone integrated with the rectus abdominis muscle. The outer cortex of calvarial bone was removed partially by bone chiseling. The muscle flap was attached to the bone graft by means of two holes on the bone by suture. The calvarial bone, grafted onto the rectus abdominis muscle flap, was inserted into the subcutaneous pocket. Several weeks later, the neovascularized calvarial bone flap was dissected along with inferior epigastric pedicle. Cranioplasty was performed using the bone element of the flap. Revascularization was achieved by anastomosing the inferior epigastric vessels to the temporal vessels. The postoperative films demonstrated marked radiolucency at the borders of the flap, although bone scan documented that the flap was vascularized. We speculate that the transferred bony segment was not completely vascularized.

Free composite latissimus dorsi muscle-rib flap not containing the intercostal artery and vein for reconstruction of bone and soft-tissue defects.

Reconstruction of bone and soft-tissue defects of the forehead and leg was done with use of a free latissimus dorsi muscle-rib flap. By utilizing the curve characteristic of the rib and by filling the cavity with latissimus dorsi muscle, the forehead could be restored in a good shape. In our application of this flap to the leg, it is considered in retrospect that reconstruction with the use of two ribs should have been done. Furthermore, it was concluded that in comparison with the heretofore employed vascularized rib graft, the scope of operative invasion is small in the use of this flap with hardly any risk of thoracostomy.

Surgical refinement of the operative procedure for a minor degree of mandibular prognathism.

Although sagittal splitting ramus osteotomy is used widely for mandibular prognathism and even for that of a minor degree, a long duration of preoperative and postoperative orthodontic treatment is required. Conversely, mandibular segmental osteotomy has often been used to correct a minor degree of mandibular prognathism without specific orthodontic treatment. Here we describe a surgical refinement accomplishing mandibular segmental osteotomy, reduction genioplasty by double horizontal osteotomies, and decortication of the middle portion of the osteotomies for a minor degree of mandibular prognathism. The amount of setback is limited to 4 to 5 mm, no intermaxillary fixation is required, and no orthodontic treatment, in principle, is needed. This procedure can obtain a rapid aesthetic improvement. We used this procedure in 11 patients (7 females and 4 males) with a minor degree of mandibular prognathism. The amount of setback of the mandibular anterior portion was 4 to 5 mm, and satisfactory results were obtained in all patients.

A reversed-flow latissimus dorsi musculocutaneous flap based on the serratus branch in primary shoulder reconstruction.

We report a case using the latissimus dorsi musculocutaneous flap based on the serratus branch in primary shoulder reconstruction. The reversed flow of the serratus branch maintained the circulation of the flap following acute disruption of the thoracodorsal vessels. Although our case was unusual, the reversed-flow latissimus dorsi flap based on its serratus branch may add a useful option in some cases.

[Maintenance chemotherapy using UFT and FT for gynecological malignant tumors. The Gunma Prefectural Society for Study of Chemotherapy for Gynecological Cancer].

The Gunma Prefectural Society for Study of Chemotherapy for Gynecological Cancer made a comparative study on postoperative supplementary chemotherapy including UFT and FT-E for gynecological malignant tumors. The number of cases registered totaled 182, which was broken down into ovarian cancer 53 cases, uterine cervical cancer 89 cases and endometrial cancer 30 cases. Complete cases among them consisted of ovarian cancer 53 cases, uterine cervical cancer 86 cases and endometrial cancer 27 cases for a total of 166 cases. Ovarian cancer was stratified into the completely and incompletely removed cases, uterine cervical cancer into postoperative non-irradiated and irradiated cases and endometrial cancer into the positive metastasis (+) group and negative metastasis (-) group. Then the UFT administration group and FT-E administration group were compared for postoperative survival. There were control groups for both ovarian and endometrial cancer. UFT administration showed a significant improvement in the survival rate (P < 0.05) compared to the FT-E administration group in the cases of ovarian cancer completely removed and the cases of endometrial cancer irradiated after operation. No significant difference was observed between other groups compared. The incidence of side effects was 20.6% (20/97) in the UFT administration group and 3.6% (2/55) in the FT-E group. Neither group showed any serious side effects.

Ultrasonographic evaluation of vincristine-induced gastric hypomotility and the prokinetic effect of mosapride in dogs.

BACKGROUND: Vincristine induces gastrointestinal motility disorders in humans. Adverse gastrointestinal events are commonly observed in dogs receiving vincristine. OBJECTIVES: To evaluate gastric motility after vincristine administration in dogs and the prophylactic effect of a prokinetic agent, mosapride. ANIMALS: Five healthy Beagle dogs. METHODS: Five dogs received vincristine i.v. at a dosage of 0.75 mg/m(2). The motility index (MI) of the antral contraction was ultrasonographically evaluated 30 minutes postfeeding before administration of vincristine and for 6 days after vincristine treatment. After a 6-week washout period, the dogs received vincristine with mosapride (2 mg/kg p.o., q24h for 6 days), and the MI was re-evaluated. Adverse gastrointestinal events were evaluated according to the Veterinary Co-operative Group Common Terminology Criteria for Adverse Events (VCOG-CTCAE). RESULTS: After vincristine administration, a significant decrease (P < .05) in MI was observed on days 3 (6.64 ± 0.30) and 4 (8.02 ± 0.94), compared with pretreatment levels (10.00 ± 0.62). Gastrointestinal adverse events were observed in 4 dogs (grade 2 decreased appetite: 3 dogs; grade 1 vomiting: 2 dogs; and grade 1 diarrhea and grade 2 hematochezia: 1 dog). When mosapride citrate was administered with vincristine and for the next 5 days, no decrease in MI was observed. Furthermore, adverse gastrointestinal events occurred less frequently (grade 1 vomiting and grade 2 hematochezia in 1 dog each). CONCLUSIONS AND CLINICAL IMPORTANCE: Vincristine (0.75 mg/m(2)) induces gastric hypomotility in dogs. Preventive administration of mosapride citrate (2.0 mg/kg p.o., q24h) improves hypomotility and may decrease the adverse gastrointestinal effects of vincristine.

[Epidemiological study on Chlamydia trachomatis infection among sexually active female adolescents].

Sexual behaviour in 141 female adolescents, from 15 to 20 (average 17.4) years old, detained in a remedial institution was investigated from an epidemiological viewpoint, with special reference to Chlamydia trachomatis (CT) infection, from April, 1985 to March, 1986. All had experienced sexual intercourse. Nineteen subjects (13.5%) were found to be CT-antigen positive by either cell cultures (16 cases) or immunofluorescence tests (9 cases). The immunotypes of CT belonged to types D-K. CT-antigen was isolated more frequently (25.5%) from girls with uterine cervicitis than from those without inflammation (5.8%) (p less than 0.001). Younger girls seemed to be more susceptible to chlamydial infection, because CT-antigen was detected at a higher rate (21.1%) in the 15-17 year age group than in the 18-20 year group (4.6%) (p less than 0.01). Anti-CT IgG antibody (CT-antibody) was found in 65 sera (46.1%). CT-antigen was detected more frequently in CT-antibody positive girls than in those with negative tests (p less than 0.001). Such results suggest that serum antibody does not effectively prevent chlamydial infections in the genital tract. The duration of persistent chlamydial infection was estimated to be from 41 to 367 days, based on the period between the last intercourse and the latest CT-antigen positive day. CT-antigen disappeared spontaneously in some girls (9 of 15) during a 100 day period of abstinence.

Microsurgical training with beads.

To assist beginners in the microsurgical practices of handling instruments and tying knots before using an animal model, the authors suggest the use of colored beads. These beads will diminish eyestrain and secondary fatigue. Also, working with colored beads might be a little more amusing and enjoyable for beginners in learning microsurgical techniques during preliminary studies to achieve the necessary orientation for working under the operating microscope.

Prefabricated osteomusculocutaneous flaps using calvarial bone: experimental study.

Prefabricated osteomusculocutaneous flaps using free calvarial bone were examined and evaluated in a rat model. The animals were divided into two groups according to prefabrication time: 14 days in Group 1 (n = 10) and 28 days in Group 2 (n = 10). Nine of 10 preparations demonstrated neovascularization in Group 1, and all flaps showed neovascularization in Group 2. One flap was lost in Group 1 as a result of infection. Each group was evaluated histopathologically before the second stage of the experiment. Muscles without atrophy and osteocytes were noted in Group 1; however, Group 2 animals had both muscle atrophy and nonviable bone. The prefabricated osteomusculocutaneous flaps were then transferred as both island and free flaps. Flap viability was assessed on postoperative day 7 by macroscopic observation. Although all flaps survived in the island-flap group, two flaps failed to survive due to technical error in the free-flap group. Neovascularization was clearly evident by 2 weeks in the osteomusculocutaneous flaps; after 4 weeks, complete atrophy of the muscle meant that the flaps could no longer be characterized as osteomusculocutaneous. Clinically, it might be possible to use the outer table alone, in which case both thin skin and bone would be desirable. This study may provide a model for this approach.

The use of otherwise redundant skin to provide nasal lining in the reconstruction of full-thickness alar defects by nasolabial flap repair.

The use of otherwise redundant nasolabial flap skin is described for lining in reconstruction of full-thickness alar defects. The techniques have been successfully used to reconstruct full-thickness alar defects in four patients. The overall procedure has the advantage of providing well-vascularised tissue of appropriate colour, texture and thickness for external skin and nasal lining in one-stage reconstruction.

An axial-pattern skin flap in the rat.

An axial-pattern rat skin flap based on the caudal femoral artery is described with orthotopic and heterotopic island flap transfers. Free-tissue transfers could also be carried out based on the common femoral artery. Since the pedicle is very small, instead of selective dye injection, a nonselective dye injection was utilized, elevating a very large island skin flap based on the caudal femoral artery. This flap model can provide an alternative opportunity to study the physiology of skin flaps and for training in the basic principles of plastic surgery, including microsurgical practice, with a more challenging model.

Nerve conduit using fascia-wrapped fibrocollagenous tube.

The purpose of this study was to evaluate the application of autogenous fascia as a framework of a fibrocollagen tube for a nerve conduit in Japanese white rabbits. The fascia was wrapped with a double layer around a silicone rod 3.0 mm in diameter. After the implantation of the fascia-wrapped silicone rod into a subcutaneous pocket for 2 weeks, a 3.0 x 30-mm fascia-wrapped fibrocollagen (FFC) tube was prepared. With microvascular techniques, the tube was interposed into a right sciatic nerve gap which was 25 mm long. The results of nerve regeneration in the FFC tube group, in particular, the formation of epineurium, were able to stand comparison with the results of a control group under both histologic and electron micrographic examination.

[Incidence of Chlamydia trachomatis isolated from endocervical columnar cells of the uterine cervix].

To study the incidence of Chlamydia trachomatis (C.T.) infection among women, we obtained swab (endocervical columnar cells) from the uterine cervix of 1,041 women attending the Department of Obstetrics and Gynecology of Gunma University Hospital. The results were as follows. 1) Overall, C.T. was isolated from 60 of the 1,041 women (5.8%). With reference to the diagnoses, the organism was isolated from 38 of 183 patients with cervicitis (20.8%) and from 22 of 858 asymptomatic womens (2.6%) (p less than 0.001). 2) C.T. antigen was detected at a higher frequency (15.0%) in the under 30 years age group than in the over 30 year age group (2.3%) (p less than 0.001). 3) The unstained inclusion C.T. bodies were confirmed more easily by phase contrast microscopy. 4) Inclusion bodies were specified as either reticulate or elementary bodies by the acridine orange staining method.

Diagnostic problems relating to uterine cervical polyps with malignancy.

In order to clarify the diagnostic problems relating to, and the proper treatment of, uterine cervical polyps, 951 polyps were analyzed clinicopathologically. All polyps were examined histopathologically and divided into 2 groups: benign polyps (Group-1), and polyps with neoplastic or malignant lesions (Group-2). Polyp size and cervical cytology are not always reliable for predicting the correct diagnosis of neoplastic or malignant lesions. Colposcopic diagnostic accuracy was 56.3%, but increased to 75.0% when combined with cytology. Neoplastic or malignant lesions were found at both the cervical polyp and the cervix in 21 out of 24 Group-2 patients (87.5%). These results suggest that in order not to miss rare neoplastic or malignant lesions in polyps and/or cervices, histopathological examinations of all polyps, aided by cervical cytology and colposcopic observation, are necessary.

Experimental vascular graft using small-caliber fascia-wrapped fibrocollagenous tube: short-term evaluation.

This study was undertaken to evaluate the application of autogenous fascia as a framework for a fibrocollagen tube for small-caliber vascular prostheses in Japanese white rabbits (n = 15). The fascia, measuring 10 x 40 mm, was harvested from the dorsal fascia and was carefully wrapped around a silicone rod of 1.5 mm in diameter. Then, the fascia-wrapped silicone rod was implanted into a subcutaneous pocket on the medial thigh. Four weeks later, the fascia-wrapped silicone rod was removed from the subcutaneous pocket. The rod was removed from the material, and the fascia-wrapped fibrocollagen tube was treated to make it antithrombogenic. Subsequently, the 1.5 x 10-mm fascia-wrapped tube was prepared as an arterial conduit. Using microvascular techniques, the tube was interposed into the divided femoral artery. Eleven of 15 grafts maintained patency over the follow-up period and no aneurysmal formation was found at any graft site. Microscopically, there was an ingrowth of endothelium with fibroblast proliferation from each end of the recipient vessel at 2 weeks after interposition; however, no neointima was found to line the center of the conduit. At 5 weeks after interposition, the neointimal growth rate was 70 percent. There was an ingrowth of endothelium with fibroblast proliferation from each end onto the entire internal surface of the conduit at 8 weeks after interposition. Further study is required before any long-term conclusions can be drawn.