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Biomedical subjects

W S Payne

Publications and source records attributed to W S Payne.

At least 19 recordsLinked to original sources

Adaptation of chimeric retroviruses in vitro and in vivo: isolation of avian retroviral vectors with extended host range.

We have designed and characterized two new replication-competent avian sarcoma/leukosis virus-based retroviral vectors with amphotropic and ecotropic host ranges. The amphotropic vector RCASBP-M2C(797-8), was obtained by passaging the chimeric retroviral vector RCASBP-M2C(4070A) (6) in chicken embryos. The ecotropic vector, RCASBP(Eco), was created by replacing the env-coding region in the retroviral vector RCASBP(A) with the env region from an ecotropic murine leukemia virus. It replicates efficiently in avian DFJ8 cells that express murine ecotropic receptor. For both vectors, permanent cell lines that produce viral stocks with titers of about 5 x 10(6) CFU/ml on mammalian cells can be easily established by passaging transfected avian cells. Some chimeric viruses, for example, RCASBP(Eco), replicate efficiently without modifications. For those chimeric viruses that do require modification, adaptation by passage in vitro or in vivo is a general strategy. This strategy has been used to prepare vectors with altered host range and could potentially be used to develop vectors that would be useful for targeted gene delivery.

Animals↗

Soluble forms of the subgroup A avian leukosis virus [ALV(A)] receptor Tva significantly inhibit ALV(A) infection in vitro and in vivo.

The interactions between the subgroup A avian leukosis virus [ALV(A)] envelope glycoproteins and soluble forms of the ALV(A) receptor Tva were analyzed both in vitro and in vivo by quantitating the ability of the soluble Tva proteins to inhibit ALV(A) entry into susceptible cells. Two soluble Tva proteins were tested: the 83-amino-acid Tva extracellular region fused to two epitope tags (sTva) or fused to the constant region of the mouse immunoglobulin G heavy chain (sTva-mIgG). Replication-competent ALV-based retroviral vectors with subgroup B or C env were used to deliver and express the two soluble tv-a (stva) genes in avian cells. In vitro, chicken embryo fibroblasts or DF-1 cells expressing sTva or sTva-mIgG proteins were much more resistant to infection by ALV(A) ( approximately 200-fold) than were control cells infected by only the vector. The antiviral effect was specific for ALV(A), which is consistent with a receptor interference mechanism. The antiviral effect of sTva-mIgG was positively correlated with the amount of sTva-mIgG protein. In vivo, the stva genes were delivered and expressed in line 0 chicken embryos by the ALV(B)-based vector RCASBP(B). Viremic chickens expressed relatively high levels of stva and stva-mIgG RNA in a broad range of tissues. High levels of sTva-mIgG protein were detected in the sera of chickens infected with RCASBP(B)stva-mIgG. Viremic chickens infected with RCASBP(B) alone, RCASBP(B)stva, or RCASBP(B)stva-mIgG were challenged separately with ALV(A) and ALV(C). Both sTva and sTva-mIgG significantly inhibited infection by ALV(A) (95 and 100% respectively) but had no measurable effect on ALV(C) infection. The results of this study indicate that a soluble receptor can effectively block infection of at least some retroviruses and demonstrates the utility of the ALV experimental system in characterizing the mechanism(s) of viral entry.

Animals↗

Surgery in the management of mediastinal carcinoid.

Primary carcinoid tumors of the mediastinum were described for the first time in 1972 as thymic carcinoids. Our experience with 16 patients who underwent diagnostic and surgical procedures at the Mayo Clinic is presented. All of these patients had mediastinal carcinoid. The surgical procedures included node biopsy, anterior mediastinotomy (Chamberlain), median sternotomy and posterior lateral thoracotomy. Complete resection was possible in 9 (56.3%) patients, 3 (18.7%) had partial removal (debulking), and 4 (25%) had diagnostic biopsies only. The operative morbidity was 25%. There were no postoperative deaths. In resectable patients, the average disease free interval was 45.7 months. Five year and ten year survival was 47% and 22%, respectively. Local or distant metastatic spread developed in all patients (100%). Mediastinal carcinoids are a separate entity from other thymic and mediastinal neoplasms. (We suggest that) Surgical excision may be possible earlier in the disease and radiation and chemotherapy are of doubtful value.

Adult↗

The treatment of pharyngoesophageal diverticulum: the simple and complex.

Over 900 patients have been treated at the Mayo Clinic for Zenker's diverticulum since 1944 using a one-stage transcervical diverticulectomy under general anesthesia. Overall results have been very good, but not entirely free of morbidity or mortality. An attempt is made to define those circumstances in which the procedures used have either been judgmentally or technically difficult or in which morbidity or mortality has occurred. These include patients with concomitant medical or surgical problems, or complexity related to the diverticulum itself. Among the latter are huge or giant sacs, patients with severe nutritional and respiratory symptoms related to aspiration, the perforated diverticulum, reoperation for recurrent diverticulum and cancer in a diverticulum.

Carcinoma, Squamous Cell↗

Screening for lung cancer. A critique of the Mayo Lung Project.

The National Cancer Institute of the United States recently sponsored three large-scale, randomized controlled trials of screening for early lung cancer. The trials were conducted at the Johns Hopkins Medical Institutions, the Memorial Sloan-Kettering Cancer Center, and the Mayo Clinic. Participants were middle-aged and older men who were chronic heavy cigarette smokers and thus at high risk of developing lung cancer. Screening procedures were chest radiography and sputum cytology, the only screening tests of established value for detecting early stage, asymptomatic lung cancer. In the Hopkins and Memorial trials the study population was offered yearly chest radiography plus sputum cytology every 4 months. The control population was offered yearly chest radiography only. In these trials the addition of sputum cytology appeared to confer no lung cancer mortality rate advantage. The Mayo Clinic trial compared offering chest radiography and sputum cytology every 4 months to offering advice that the two tests be obtained once a year. This trial demonstrated significantly increased lung cancer detection, resectability, and survivorship in the group offered screening every 4 months compared with the control group. However, there was no significant difference in lung cancer mortality rate between the two groups. The statistical power of these trials was somewhat limited. Nevertheless, results do not justify recommending large-scale radiologic or cytologic screening for early lung cancer at this time.

Clinical Trials as Topic↗

An integrated approach to evaluation of the solitary pulmonary nodule.

In this article, we describe an integrated approach for detection and evaluation of solitary pulmonary nodules. Initial evaluation of the solitary pulmonary nodule includes tomography, fluoroscopy, and comparison with previously obtained roentgenograms. Subsequently, thin-section computed tomography and phantom densitometry can be used for analysis, if indicated. The rationale for the use of computed tomography in the radiologic staging of bronchogenic carcinoma is to expedite and assist in the identification of the subset of patients with resectable tumors. For nonsurgical tissue diagnosis, fiberoptic bronchoscopy is generally the initial procedure for lesions 2.0 cm or larger in diameter, and transthoracic needle biopsy is used for those smaller than 2.0 cm.

Biopsy, Needle↗

Primary pulmonary artery sarcoma. A method of resection.

Primary pulmonary artery sarcoma classically presents with symptoms and findings suggestive of acute pulmonary artery occlusion. An angiocentric mass or the finding of spindling neoplasm on needle biopsy should suggest this neoplasm. The rare unilateral location in the present case permitted resection by pneumonectomy. An endarterectomy technique was used to extract loosely adherent tumor-thrombus from the more proximal portions of the left pulmonary artery.

Female↗

Multiple primary lung cancers. Results of surgical treatment.

During a 13-year period, multiple primary lung cancers were diagnosed in 80 consecutive patients. Forty-four patients had metachronous cancers. The initial pulmonary resection was lobectomy in 36 patients, bilobectomy in 3, pneumonectomy in 1, and wedge excision or segmentectomy in 4. The second pulmonary resection was lobectomy in 16 patients, bilobectomy in 2, completion pneumonectomy in 7, and wedge excision or segmentectomy in 19. There were two 30-day operative deaths (mortality rate, 4.5%). Actuarial 5- and 10-year survival rates after the first pulmonary resection for stage I disease were 55.2% and 27.0%, respectively. Five-year and 10-year survival rates for stage I disease after the second pulmonary resection were 41.0% and 31.5%, respectively. The remaining 36 patients had synchronous cancers. The pulmonary resection was lobectomy in 18 patients, bilobectomy in 3, pneumonectomy in 10, and wedge excision or segmentectomy in 8. There were two 30-day operative deaths (mortality rate, 5.6%). Actuarial overall 5- and 10-year survival rates after pulmonary resection were 15.7% and 13.8%, respectively. We conclude that an aggressive surgical approach is safe and warranted in most patients with multiple primary lung cancers and that the presence of synchronous primary cancers is ominous.

Adult↗

Cryopreservation of canine trachea: functional and histological changes.

The purpose of this study was to evaluate tracheal viability and to document histological changes in an autograft implanted in the abdominal wall after a 1-week period of cryopreservation. A 5-cm segment of cervical trachea was resected in 6 dogs. One-half of the segment was cryopreserved and stored in liquid nitrogen at -196 degrees C for 1 week. The other half was immediately implanted in an abdominal pouch fashioned from the rectus abdominis muscle (control). One week later, the cryopreserved segment was thawed and then implanted in a similar contralateral muscular pouch. Five weeks later, the control and cryopreserved autografts were removed and compared with the in situ trachea. Ciliary beat frequency was assessed by transmitted light technique. Histology was evaluated by light microscopy. Gross anatomy and mucus production were maintained after cryopreservation. Histologically the cryopreserved segment displayed both normal epithelium and smooth muscle cells, but the cartilage was abnormal as characterized by empty lacunae. Mean ciliary beat frequency of in situ, control, and cryopreserved segments was 13.3 +/- 1.8, 13.5 +/- 1.5, and 13.3 +/- 1.1 beats per second (+/- the standard deviation), respectively. We conclude that smooth muscle, epithelium with mucus production, and ciliary function were retained after cryopreservation and reimplantation. Histological changes, however, were suggestive of early cartilage ischemia. These findings support further evaluation of cryopreserved canine tracheal grafts.

Animals↗

The effectiveness of fibrin glue sealant for reducing experimental pulmonary ari leak.

The effectiveness of fibrin glue as a biological sealant for pulmonary air leaks was determined in 16 dogs. A standardized pleural defect was made in the left lower lobe, and the quantity of air passing through a chest tube was assessed with a Collins respirometer. For the 8 randomly assigned control animals, the air leak decreased over 90 minutes from a mean of 1.4 L/min to a mean of 1.1 L/min (mean decrease, 19.8%). In the 8 randomly assigned fibrin glue-treated animals, the air leak decreased from a mean of 2.1 L/min to a mean of 0.5 L/min (mean decrease, 80.8%) (p less than 0.0001). Postoperative evaluation of survivors disclosed no increased adhesions in the glue-treated animals and complete resorption of the glue at 3 months. We conclude that in this animal model, fibrin glue reduced the size of pulmonary air leaks in the early period after thoracotomy and did not lead to increased intrapleural adhesions.

Animals↗

An unusually intractable Schatzki ring.

Most patients with Schatzki's ring have dysphagia that can be relieved by esophageal dilation. We report an unusual case in which dysphagia caused by a Schatzki ring could not be managed conservatively. The obstructing ring was excised through a gastrotomy approached by a left-sided thoracotomy. An antireflux procedure was done after elimination of the ring. Five years later, the patient remained symptom free.

Aged↗

Completion pneumonectomy: indications, complications, and results.

From 1958 through 1985, a total of 113 consecutive patients had completion pneumonectomy (CP). Indications for pulmonary resection resulting in CP were lung cancer (LC) in 64 patients, pulmonary metastases (PM) in 20, and benign lung disease (BLD) in 29. Operative mortality was 12.4% (14 deaths) but varied according to the indication for CP. Mortality was 9.4% for LC, 0% for PM, and 27.6% for BLD. Forty-three patients (38.1%) had major complications (26 of 64 with LC, 40.6%; 1 of 20 with PM, 5.0%; and 16 of 29 with BLD, 55.2%). Five-year actuarial survival for patients with LC was 26.4% but varied according to stage. Five-year survival for patients with PM was 40.8% and with BLD was 27.2%. We conclude that CP for BLD carries marked operative mortality and morbidity, usually due to intense reaction around hilar structures and concurrent active infection or fistula. In contrast, CP for LC and PM can be performed with low mortality, acceptable morbidity, and gratifying long-term survival.

Actuarial Analysis↗

Ivor Lewis esophagogastrectomy for carcinoma of the esophagus: early and late functional results.

One hundred adult patients underwent Ivor Lewis esophagogastrectomy for documented carcinoma of the esophagus from 1980 through 1982. After operation, 7 patients were classified in Stage I, 11 in Stage II, and 82 in Stage III. Major postoperative complications occurred in 27 patients and included pulmonary problems in 11, suture line leak in 9, wound infection in 5, empyema in 4, renal failure in 4, abdominal abscess in 4, bleeding in 2, myocardial infarction in 2, and chylothorax in 1. There were 3 deaths within 30 days of operation. Five-year survival was 85.7% for patients with Stage I disease, 34.1% for patients with Stage II disease (p = .052), and 15.2% for patients with Stage III disease (p = .001). Late morbidity included weight loss in 60 patients, dysphagia in 40, gastroesophageal reflux in 14, and gastroduodenal dumping in 5. Thirty-one patients required postoperative esophageal dilations (mean, 3.4). Most patients, however, were eating without dysphagia at the time of last follow-up or death. We conclude that the Ivor Lewis esophagogastrectomy can be performed with low mortality, can provide adequate palliation, and does result in satisfactory long-term survival for those patients with more favorable postsurgical stages of cancer. These results support the continued use of the Ivor Lewis esophagogastrectomy for treatment of carcinoma of the esophagus.

Adenocarcinoma↗

Reflux esophagitis.

Reflux esophagitis and its complications are not only common clinical problems but also problems that can be accurately defined by careful history taking and a knowledge of the pathophysiology of the various manifestations. An element of objective assessment, however, is required to define and substantiate fully an individual patient's problem. Only when disabling subjective and intractable objective complications persist after good medical treatment should surgical intervention be considered. Various antireflux procedures are currently available and all can be effective. Surgeons should review their own experiences and make alterations that they perceive will correct the types of problems encountered. In our current technique for the surgical management of gastroesophageal reflux in the common clinical setting, normal esophageal peristalsis is present, the fundus is adequate for plication, and sufficient esophageal mobilization can be effected to permit reduction of the entire stomach and fundoplication below the diaphragm. In addition, the procedure should be restricted to patients who do not have stenosis or have stenosis that can be readily dilated to 50 French.

Esophageal Stenosis↗

Treatment of bronchogenic carcinoma with chest wall invasion.

En bloc resection of chest wall and lung for primary non-small cell bronchogenic carcinoma with chest wall invasion, although often associated with a significant operative mortality, can be performed with a reasonable expectation of long-term survival if lymph nodes are not metastatically involved. Older age appears to decrease long-term survival, but age alone should not abrogate surgical resection. Non-small cell carcinoma cell type, tumor size, depth of chest wall invasion, and extent of chest wall or lung resection do not significantly influence survival.

Adult↗