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L R Kaiser

Publications and source records attributed to L R Kaiser.

At least 73 records · Page 4Linked to original sources
PubMed1998

Gene therapy for malignant pleural mesothelioma.

Malignant mesothelioma (MM) is a fatal malignancy refractory to all forms of standard anticancer therapy. This article reports the results of a phase I clinical trial assessing the safety of intrapleural delivery and efficacy of intratumoral gene transfer of recombinant adenovirus (rAd) containing herpes simplex virus thymidine kinase (HSVtk) gene into the pleural space of patients with MM, followed by systematic treatment with the antiviral drug ganciclovir (GCV) for 14 days. AD.RSVtk/GCV gene therapy proved to be well tolerated, with evidence of significant gene transfer particularly at high vector doses and with elimination of preliminary biopsy. Ongoing gene therapy trials for mesothelioma at two other centers, focusing on immunostimulation and using suicide gene therapy as a tumor vaccine, are also reviewed in this article.

Cancer Vaccines↗
PubMed1998

Comparison of short-term functional outcomes following unilateral and bilateral lung volume reduction surgery.

STUDY OBJECTIVES: To compare short-term functional outcomes following unilateral and bilateral lung volume reduction surgery (LVRS) performed in patients with advanced emphysema. METHODS: LVRS was performed unilaterally in 32 patients and bilaterally in 119 patients. Pulmonary function testing and 6-min walk test (6MWT) were performed preoperatively and repeated at 3 to 6 months postoperatively. RESULTS: Bilateral LVRS was associated with increased in-hospital mortality (10% vs 0%, p<0.05) and a higher incidence of postoperative respiratory failure (12.6% vs 0%; p<0.05) compared with unilateral LVRS. There was no significant difference in duration of air leaks between unilateral and bilateral groups, but the mean hospital stay was significantly longer following bilateral LVRS (21.1+/-32.0 days vs 14.2+/-14.0 days; p<0.05). Preoperatively, there was no significant difference between the unilateral and bilateral groups with respect to FEV1, FVC, residual volume, or 6MWT distance. However, for all of these parameters, the magnitude of improvement was significantly greater following bilateral LVRS. Notably, the magnitude of improvement in each parameter following unilateral LVRS exceeded half that following bilateral LVRS, suggesting that functional outcomes after the unilateral procedure were disproportionate to the amount of tissue resected. Serial functional assessment of seven patients undergoing staged unilateral procedures (two unilateral procedures separated in time by at least 3 months) demonstrated somewhat unpredictable responses; failure to achieve a favorable response to the initial procedure did not necessarily portend a similar outcome with the contralateral side, and vise versa. CONCLUSIONS: Bilateral LVRS produces a greater magnitude of short-term functional improvement than does the unilateral procedure and should be considered the procedure of choice for most patients. Unilateral LVRS should be reserved for patients in whom factors contraindicating entrance into one hemithorax exist.

Endoscopy↗
PubMed1998

Primary graft failure following lung transplantation.

STUDY OBJECTIVES: To determine the incidence of primary graft failure (PGF) following lung transplantation, assess possible risk factors, and characterize its effect on outcomes. METHODS: Retrospective review of 100 consecutive patients undergoing lung transplantation at the University of Pennsylvania Medical Center. Fifteen patients meeting diagnostic criteria for PGF (PGF+ group) were compared with 85 patients without this complication (PGF- group). RESULTS: The incidence of PGF was 15%. There was no significant difference in age, sex, underlying pulmonary disease, preoperative pulmonary artery systolic pressure, type of transplant, allograft ischemic times, use of cardiopulmonary bypass, or use of postoperative prostaglandin E1 infusion between the PGF+ and PGF- groups. Induction therapy with antilymphocyte globulin was used less frequently in the PGF+ group (p<0.005). Duration of mechanical ventilatory support was 36+/-43 days vs 4+/-6 days for the PGF+ and PGF- groups, respectively (p<0.0001). Hospital stay was significantly longer in the PGF+ group, averaging 75+/-105 days, compared with 27+/-38 days in the PGF group (p<0.005). One-year actuarial survival for the PGF+ group was only 40% compared with 69% for the PGF- group (p<0.005). Five of the six PGF+ survivors were ambulatory by 1 year; three were completely independent while two continued to require assistance with activities of daily living. Six-minute walk test distance among the ambulatory patients averaged 883+/-463 feet (range, 200 to 1,223 feet) compared with 1513+/-424 feet for the PGF- group (p<0.005). Among the subset of survivors who underwent single lung transplantation for COPD, the mean percent predicted FEV1 at 1 year was 43% for the PGF+ group and 55% for the PGF- groups, but this difference was not statistically significant. CONCLUSIONS: PGF is a devastating postoperative complication, occurring in 15% of patients in the current series, and it is associated with a high mortality rate, lengthy hospitalization, and protracted and often compromised recovery among survivors.

Activities of Daily Living↗
PubMed1998

Mediastinoscopic subtotal removal of mediastinal cysts.

STUDY OBJECTIVE: Evaluate the use of mediastinoscopy in the surgical diagnosis and treatment of mediastinal cystic masses in adults. DESIGN: Case reports and literature review. SETTING: Academic department of surgery. PATIENTS: Three consecutive adults with mediastinal masses identified on plain radiographs and CT. INTERVENTIONS: Operative mediastinoscopy. MEASUREMENTS AND RESULTS: All patients were successfully treated with removal of cyst wall, establishment of diagnosis, and same-day hospital discharge. CONCLUSIONS: Simple mediastinoscopic removal of mediastinal cysts offers the same potential for diagnosis and treatment as more conventional methods, with a potential for less morbid and more cost-effective care.

Adult↗
PubMed1998

Metabolic imaging of malignant pleural mesothelioma with fluorodeoxyglucose positron emission tomography.

BACKGROUND: The diagnosis of malignant mesothelioma is a challenging medical problem. CT often cannot differentiate between benign diffuse pleural thickening and malignant mesothelioma, while thoracentesis and CT-guided biopsies are insensitive. We have assessed the value of positron emission tomography (PET) with 2-fluoro-2-deoxy-D-glucose (FDG) in the evaluation of malignant mesothelioma. METHODS: Twenty-eight consecutive patients referred for the evaluation of suspected malignant mesothelioma were evaluated by FDG-PET imaging. Measured attenuation correction was performed in 26 of 28 cases for quantitation with the standardized uptake value (SUV) method. The results of PET imaging were compared with those of video-assisted thoracoscopy or surgical biopsies. RESULTS: Surgical biopsy specimens confirmed the presence of malignant disease in 24 patients and demonstrated benign processes in the remaining four. The uptake of FDG was significantly higher in malignant than in benign lesions (SUV=4.9+/-2.9 and SUV=1.4+/-0.6, respectively; p<0.0001). With a SUV cutoff of 2.0 to differentiate between malignant and benign disease, a sensitivity of 91% and a specificity of 100% could be achieved, although the activity in some epithelial mesotheliomas tended to be close to this threshold. FDG-PET images provided excellent delineation of the active tumor sites. Hypermetabolic lymph node involvement was noted on FDG-PET images in 12 patients, 9 of which appeared normal on CT scans. Histologic examination in six patients confirmed malignant nodal disease in five cases and indicated granulomatous lymphadenitis in one. CONCLUSION: In this highly selected population, FDG-PET imaging was a sensitive method to identify malignant mesothelioma and determine the extent of the disease process.

Biopsy↗
PubMed1998

Tithing: why now?

Explore the source record for details and available documents.

Charities↗
PubMed1998

Cancer chemotherapy using suicide genes.

Suicide gene therapy is a unique form of drug delivery system that allows for negative selection of malignant cells using a prodrug approach. Malignant cells are transduced with a gene encoding an enzyme that can metabolize an otherwise nontoxic prodrug into a toxic metabolite. The prototype of this system is the herpes simplex virus thymidine kinase gene (HSV-tk). Suicide genes may be introduced into tumor cells either by viral vectors or nonviral methods. Current work is underway to fine tune both the delivery systems and optimize the efficacy of the production of the toxic metabolites. Suicide gene therapy is an exciting strategy currently in clinical trial in the treatment of a number of tumors.

Antineoplastic Agents↗
PubMed1997

Use of a "replication-restricted" herpes virus to treat experimental human malignant mesothelioma.

Modified, nonneurovirulent herpes simplex viruses (HSVs) have shown promise in the treatment of brain tumors. However, HSV-1 can infect and lyse a wide range of cell types. In this report, we show that HSV-1716, a mutant lacking both copies of the gene coding ICP-34.5, can effectively treat a localized i.p. malignancy. Human malignant mesothelioma cells supported the growth of HSV-1716 and were efficiently lysed in vitro. i.p. injection of HSV-1716 into animals with established tumor nodules reduced tumor burden and significantly prolonged survival in an animal model of non-central nervous system-localized human malignancy without dissemination or persistence after i.p. injection into SCID mice bearing human tumors. These findings suggest that this virus may be efficacious and safe for use in localized human malignancies of nonneuronal origin such as malignant mesothelioma.

Animals↗
PubMed1997

Loss of alpha-v integrin expression and recurrence in node-negative lung carcinoma.

BACKGROUND: Despite "curative" resection, metastases develop in many patients with node-negative (N0) non-small cell lung carcinoma. Alternative biologic markers for this tumor would be useful. Integrins are cell adhesion molecules that are thought to be important in tumor progression, and expression of these molecules previously has been shown to be altered in non-small cell lung carcinoma. We evaluated alterations in integrin expression and clinical outcome. METHODS: Immunohistochemical staining of tumor specimens was performed, and clinical data were reviewed retrospectively. RESULTS: Data were complete for 42 patients. Half of all patients (21/42) and 9 of 26 patients with negative nodes experienced tumor recurrence during follow-up. Neither histologic type nor tumor differentiation status correlated with recurrence. However, loss of the alpha v integrin subunit was associated significantly with recurrence in the N0 group. Seventy-five percent of patients with negative nodes who exhibited recurrence lost alpha v expression, compared with only 10% of patients with negative nodes who did not exhibit recurrence (p = 0.012). Alterations of other integrin subunits did not correlate significantly with prognostic follow-up variables. CONCLUSIONS: Loss of alpha v expression may serve as a marker for patients with node-negative non-small cell lung carcinoma who are at high risk for recurrence, potentially directing additional therapies.

Antibodies, Monoclonal↗
PubMed1997

Fatal hyperammonemia following orthotopic lung transplantation.

There have been anecdotes of unexplained coma and death in patients after otherwise successful orthotopic lung transplantation. A patient with primary pulmonary hypertension who underwent a technically uncomplicated single orthotopic lung transplantation is described. The patient developed intractable status epilepticus 4 days after surgery in association with the presence of a markedly elevated plasma ammonium level. Despite multiple therapeutic interventions, the hyperammonemia ultimately resulted in the patient's death. Both metabolic and enzymatic studies showed that the unique physiological disturbance in this disorder results at least in part from defective in vivo conversion of waste nitrogen to urea and increased production of waste nitrogen. Although the rate of hepatic ureagenesis was therefore insufficient to prevent accumulation of ammonium, the cause was not severe liver disease. Liver histology showed widespread, microvesicular steatosis on light-microscopic examination, but only electron-microscopic examination showed severe microvesicular steatosis with severe mitochondrial injury. As in Reye's syndrome, it was unclear whether the hepatic mitochondrial injury played a role in development or if it was the result of hyperammonemia. We recommended that any patient with an unexplained alteration of mental status after solid organ transplantation be evaluated for hyperammonemia.

Ammonia↗
PubMed1997

Bilateral versus single lung transplantation for chronic obstructive pulmonary disease.

OBJECTIVE: Traditionally, despite ventilation/perfusion mismatch, single lung transplantation has been the mainstay for end-stage chronic obstructive pulmonary disease. We tested the hypothesis that bilateral sequential lung transplantation has better short- and intermediate-term results than single lung transplantation for chronic obstructive pulmonary disease. METHODS: One hundred twenty-six consecutive lung transplants have been performed from November 1991 to March 1996. Seventy-six have been for chronic obstructive pulmonary disease. The diagnosis of this disease includes emphysema (80.3%), alpha 1-antitrypsin deficiency (9.2%), lymphangioleiomyomatosis (7.9%), and obliterative bronchiolitis (2.6%). Twenty-nine transplants have been bilateral and 47 have been single. Mean age was 55.3 for patients having single lung transplantation and 48.8 for those having bilateral lung transplantation (p = 0.001). The distribution of the diagnoses was similar between the two groups. At 6 months, there were 29 survivors of single lung transplantation and 20 survivors of bilateral lung transplantation, with complete data for evaluation. Pulmonary function tests and 6-minute walk tests were evaluated at a mean of 15.4 and 12.8 months after transplantation, respectively. RESULTS: Sixty-day mortality was 21.3% for single lung transplantation versus only 3.45% for bilateral lung transplantation (p = 0.03). Additionally, Kaplan-Meier analysis revealed 1- and 2-year survivals of 71.1% and 63.3% for single lung transplantation versus 90% and 90% for bilateral lung transplantation, respectively. Multiple major morbidities were analyzed. Primary graft failure was significantly reduced in the bilateral group (p = 0.049). Both 6-minute walk tests and forced expiratory volume in 1 second were improved from baseline by both single and bilateral lung transplantation (p = 0.001). CONCLUSIONS: Bilateral lung transplantation improves forced expiratory volume in 1 second and 6-minute walk tests significantly over single lung transplantation (p < 0.0001). Both perioperative mortality and Kaplan-Meier survival (to 3 years) are significantly improved when bilateral rather than single lung transplantation is used for chronic obstructive pulmonary disease in our series (p < 0.05). This is probably the result of significantly reduced primary graft failure.

Aged↗
PubMed1997

Retinoids augment the bystander effect in vitro and in vivo in herpes simplex virus thymidine kinase/ganciclovir-mediated gene therapy.

Metabolic cooperation via gap junctional intercellular communication (GJIC) is an important mechanism of the bystander effect in gene therapy using the herpes simplex virus thymidine kinase/ganciclovir (HSVtk/GCV) 'prodrug' system. Since retinoids have been reported to increase GJIC by induction of connexin expression, we hypothesized that these compounds could be used to augment the HSVtk/GCV bystander effect. Addition of all-trans retinoic acid increased GJIC in tumor cell lines, augmented expression of connexin 43, and was associated with more efficient GCV-induced in vitro bystander killing in cells transduced with HSVtk via either retrovirus or adenovirus vectors. This augmentation of bystander effect could also be seen in vivo. HSVtk-transduced tumors in mice treated with the combination of GCV and retinoids were significantly smaller than those treated with GCV or retinoids alone. These results provide evidence that retinoids can augment the efficiency of cell killing with the HSVtk/GCV system by enhancing bystander effects and may thus be a promising new approach to improve responses in gene therapy utilizing the HSVtk/GCV system to treat tumors or vascular restenosis.

Animals↗
PubMed1997

Thoracoscopic management of descending necrotizing mediastinitis.

Descending necrotizing mediastinitis (DNM) is a lethal process originating from odontogenic, pharyngeal, or cervical infectious sources that descends along fascial planes into the mediastinum. Despite earlier use of antibiotics and surgical drainage, the mortality (>50%) has changed little since the first large series reported in the preantibiotic era. The surgical management remains controversial, with support ranging from cervical drainage alone to cervical drainage and routine thoracotomy. We report a case of thoracoscopic drainage and debridement of a mediastinal abscess resulting from descending necrotizing mediastinitis. The decreased morbidity of this approach compared with posterolateral thoracotomy and the improved drainage of the mediastinum compared with cervical drainage support this method as an attractive management of patients with DNM.

Abscess↗
PubMed1997

Bilateral sequential lung transplantation for pulmonary alveolar microlithiasis.

Pulmonary alveolar microlithiasis (PAM) is characterized by deposition of calcium phosphate within the alveolar airspaces. There is currently no effective medical therapy and affected individuals may progress to end-stage lung disease requiring transplantation. Two patients with PAM underwent bilateral sequential lung transplantation. This study reviews the clinical manifestations of PAM and discusses the particular difficulties that may be encountered in the use of lung transplantation as treatment for this uncommon disease. Also addressed is the question of recurrence in the allograft.

Adult↗
PubMed1997

Epidemiology of lung cancer.

Lung cancer is the leading cause of cancer deaths for men and women in the United States, accounting for more cancer deaths since 1930 than all other cancer deaths combined. Whereas primary lung cancer was a relatively rare malignancy in the early 1900s, in 1994 there were approximately 170,000 new cases of lung cancer in the United States, of which roughly 100,000 were in men and 70,000 were in women. Despite numerous medical and surgical advances in the past several decades, there has not been a dramatic increase in the percentage of patients being cured of this lethal disease. Smoking is the primary factor responsible for the lung cancer epidemic, but there are numerous other environmental and genetic factors that have been implicated in the pathogenesis of the disease. Recently, it has become evident that passive smoking may also play a significant role in the development of lung cancer. Although screening has not been proven effective in the past, it may be time to reevaluate this technique because early detection of lung cancer affords the best chance for cure.

Female↗
PubMed1997

The role of surgery in the multimodality management of non-small cell lung cancer.

The majority of patients with lung cancer have disseminated disease at the time of presentation. For the minority of patients with disease localized to the chest, the concept of staging becomes particularly important because it has a major impact on the treatment plan. Guided by findings on the computed tomographic scan, mediastinoscopy remains the definitive invasive staging procedure to document unequivocally the involvement of the mediastinal lymph nodes. Equally as important is the documentation of absence of disease in contralateral lymph nodes. Patients with locally advanced non-small cell lung cancer, especially those with involvement of mediastinal lymph nodes (N2), are candidates for a multimodality approach to treatment involving either chemotherapy alone or in combination with radiation therapy. Surgical excision may be important in the management of these patients after an induction regimen. If surgical excision is performed, complete excision is the single most important factor. Postoperative adjuvant therapy may reduce the incidence of local recurrence but has not been shown to improve survival.

Carcinoma, Non-Small-Cell Lung↗