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Biomedical subjects

J A Kern

Publications and source records attributed to J A Kern.

At least 73 records · Page 4Linked to original sources
PubMed1995

Anesthetic techniques for pediatric thoracoscopy.

BACKGROUND: Since 1981, we have performed 68 thoracoscopic procedures in 62 patients aged 7 months to 21 years. METHODS: We reviewed the anesthetic and ventilation strategy used for each procedure to determine which anesthetic strategies are safe and effective for particular children and conditions. RESULTS: Regional anesthesia with sedation was used for six procedures in 5 patients with a mean age of 16 years (range, 9 to 21 years). One patient required conversion to general anesthesia. General anesthesia with one-lung ventilation was attempted for 18 procedures in 17 patients with a mean age of 12 years (range, 7 months to 18 years). Two patients required conversion to two-lung anesthesia secondary to pulmonary intolerance. One of these patients and 2 others required thoracotomy. General anesthesia with two-lung ventilation was used for 44 procedures in 41 patients with a mean age of 9 years (range, 1 to 17 years). There were no anesthesia-related difficulties. CONCLUSIONS: Regional anesthesia should be limited to the older, more cooperative patient. General anesthesia with one-lung ventilation is useful in adolescents, as they tolerate collapse of one lung well, and it is particularly desirable for procedures requiring exposure of the mediastinum and for talc pleurodesis. General anesthesia with two-lung ventilation can be used in any age group but is generally necessary for infants and small children, as they often will not tolerate the collapse of one lung, and in the larger child or adolescent with severe pulmonary compromise.

Adolescent↗
PubMed1995

Endogenous human renin expression and promoter activity in CALU-6, a pulmonary carcinoma cell line.

We have previously reported that transgenic mice containing the human renin gene express high levels of human renin mRNA in the lung. We show in this report that human renin expression in two lines of transgenic mice is developmentally regulated. Human renin expression is not evident in the transgenic mouse lung at 15.5 days of gestation, is detectable at 17.5 days of gestation, peaks around birth, and remains elevated into adulthood. In situ hybridization of mouse fetal lung samples at 18.5 days of gestation revealed that human renin was exclusively expressed in pulmonary type II epithelial cells. A survey of the medical literature revealed a number of clinical cases in which hypertension was caused by renin-secreting pulmonary tumors and a fairly widespread occurrence of immunoreactive renin in banked pulmonary tumors of diverse origin. This prompted us to examine a number of pulmonary tumor cell lines to determine whether they express human renin mRNA. One pulmonary carcinoma cell line, CALU-6, expressed human renin mRNA endogenously. Human renin expression in these cells was induced approximately 100-fold after treatment with forskolin, 8-bromoadenosine 3':5'-cyclic monophosphate, or N6,2'-O-dibutyryladenosine 3':5'-cyclic monophosphate. Transfection analysis of human renin promoter-luciferase fusion constructs revealed the presence of cell-specific positive and negative regulatory elements in the human renin 5'-flanking DNA. This cell line is the only immortalized human cell line that expresses high levels of endogenous human renin mRNA and should provide an excellent tool for studying the regulation of human renin expression in vitro.

Animals↗
PubMed1995

Predicting postoperative pulmonary function in patients undergoing lung resection.

OBJECTIVE: Our aim was to determine the effect of lung resection on spirometric lung function and to evaluate the accuracy of simple calculation in predicting postoperative pulmonary function in patients undergoing lung resection. DESIGN: We reviewed preoperative and postoperative pulmonary function test results on patients who were followed in the multidisciplinary lung cancer clinic between July 1991 and March 1994 and who underwent lung resection. The predicted postoperative FEV1 and FVC were calculated based on the number of segments resected and were compared with the actual postoperative FEV1 and FVC. SETTING: This study was conducted at a university, tertiary referral hospital. PATIENTS: All patients were evaluated at a multidisciplinary lung cancer clinic and underwent lung resection by one surgeon (L.A.L.). MEASUREMENTS AND MAIN RESULTS: Sixty patients undergoing 62 pulmonary resections were reviewed. The predicted postoperative FEV1 and FVC were calculated using the following formula: predicted postoperative FEV1 (or FVC) = preoperative FEV1 (or FVC) x (1-(S x 0.0526)); where S = number of segments resected. The actual postoperative FEV1 and FVC correlated well with the predicted postoperative FEV1 and FVC for patients undergoing lobectomy (r = 0.867 and r = 0.832, respectively); however, the predicted postoperative FEV1 consistently underestimated the actual postoperative FEV1 by approximately 250 mL. For patients undergoing pneumonectomy, the actual postoperative FEV1 and FVC did not correlate as well with the predicted postoperative FEV1 and FVC (r = 0.677 and r = 0.741, respectively). Although there was considerable variability, the predicted postoperative FEV1 consistently underestimated the actual postoperative FEV1 by nearly 500 mL. Of the patients undergoing lobectomy, eight also received postoperative radiation therapy. When analyzed separately, patients receiving combined therapy lost an average of 5.47% of FEV1 per segment resected. This contrasts with a 2.84% per segment reduction in FEV1 for patients who did not receive radiation therapy. CONCLUSIONS: This simple calculation of predicted postoperative FEV1 and FVC correlates well with the actual postoperative FEV1 and FVC in patients undergoing lobectomy. The predicted postoperative FEV1 consistently underestimated the actual postoperative FEV1 by approximately 250 mL. The postoperative FEV1 and FVC for patients undergoing pneumonectomy is not accurately predicted using this equation. The predicted postoperative FEV1 for patients undergoing pneumonectomy was underestimated by an average of 500 mL and by greater than 250 mL in 12 of our 13 patients. Thus, by adding 250 mL to the above calculation of predicted postoperative FEV1, we improve our ability to we identify a minimal postoperative FEV1 for patients undergoing pneumonectomy. Finally, combined modality treatment with surgery followed by radiation therapy may result in additive lung function loss.

Adult↗
PubMed1994

Analysis of airway function of immature whole lung transplants versus mature lobar transplants.

For the pediatric patient with end-stage lung disease in need of transplantation, two potential donor options currently exist: size-matched immature whole lungs or reduced-size mature lobes. To determine which of these options provides superior long-term function, we studied airway mechanics in a chronic porcine model of pediatric lung transplantation. Three groups of animals were studied: the first group underwent left upper lobectomy at 9 +/- 1 weeks of age (innervated left lower lobes). These animals served as controls. A second group of 9-week-old animals received an immature whole left lung allograft from age-matched donors. The third group received a reduced-size mature left lower lobe from 6-month-old donors. Measurements of dynamic airway resistance, pulmonary compliance, and functional residual capacity of the isolated lobes or lungs, and of the nonoperated right lungs, were recorded 12 +/- 1 weeks later, and mean values were calculated for each group. Results showed that transplantation of an immature whole lung resulted in abnormal dynamic airway resistance to airflow, which was not seen in the mature lobar transplants. In addition, compliance was impaired most significantly in the immature whole lung transplants. We conclude that in this experimental model of pediatric lung transplantation, transplantation of a mature lobar segment results in superior long-term airway function when compared with immature whole lung transplants.

Age Factors↗
PubMed1994

C-erbB-2 expression and codon 12 K-ras mutations both predict shortened survival for patients with pulmonary adenocarcinomas.

We evaluated the prognostic significance of p185c-erbB-2 expression and ras gene mutations in all patients diagnosed with a pulmonary adenocarcinoma between 1982 and 1985 at the University of Iowa. p185c-erbB-2 expression was detected in 15 cases (34%). A ras gene mutation was found in 16 cases (36%) and all were in codon-12 of K-ras. No N-ras mutations were identified. Both p185c-erbB-2 expression and a K-ras mutation were found only in codon-12 and present in six cases (14%). By univariate analysis p185c-erbB-2 expression was associated with shortened survival (P = 0.02) while the presence of a K-ras mutation was not (P = 0.16). Multivariate analysis by the Cox proportional hazards model, controlling for patient age and tumor stage, also continued to identify p185c-erbB-2 expression as an independent unfavorable prognostic factor (P = 0.01). In this model a K-ras mutation also approached significance as a poor prognostic indicator (P = 0.06). The impact of both p185c-erbB-2 expression and a K-ras mutation on survival was additive and highly significant (P = 0.004). This additive nature suggests that together these two markers identify a high-risk population of lung adenocarcinoma patients that may benefit from aggressive therapy.

Actuarial Analysis↗
PubMed1993

Impairment of vascular endothelial function by high-potassium storage solutions.

High-potassium cold storage solutions are currently used to preserve myocardial function during heart transplantation. However, the effects of high potassium concentration on vascular endothelial function are not well known. We therefore tested vascular rings for endothelial-dependent and endothelial-independent relaxation during storage in normokalemic, normothermic buffers and then in buffers supplemented with 10 to 110 mmol/L KCl. Maximal endothelial-dependent relaxation was significantly reduced at all high potassium concentrations. Endothelial-independent relaxation was impaired only with 80 and 110 mmol/L KCl buffers. Both endothelial-dependent relaxation and endothelial-independent relaxation returned to normal values after washout of excess potassium. Similarly, endothelial-dependent relaxation and endothelial-independent relaxation were assessed in rings after 24 hours of hypothermic storage in normokalemic Krebs buffer, and in buffers containing 20 and 110 mmol/L KCl. Maximal endothelial-dependent relaxation was significantly reduced after preservation in the high-potassium solutions, whereas endothelial-independent relaxation was not impaired. We conclude that there is significant impairment of endothelial function after cold storage in a high-potassium buffer. Inadequate washout of potassium during normothermic conditions may lead to further functional impairment of vascular responsiveness. A low-potassium storage medium is recommended for improved vascular protection.

Animals↗
PubMed1993

Thoracoscopic diagnosis and treatment of mediastinal masses.

Evaluation of mediastinal masses often involves an array of imaging procedures and percutaneous biopsy techniques. Despite this, surgical intervention with an open biopsy is often required, especially to diagnose mediastinal malignancies. We report 22 patients with mediastinal masses who were managed with thoracoscopic biopsy, as opposed to open biopsy. All of these patients either had unsuccessful fine-needle aspiration or were unacceptable candidates for percutaneous aspiration. The patients ranged in age from 11 months to 67 years with a mean age of 17.2 +/- 3.6 years. Thoracoscopy provided an accurate tissue diagnosis in 19 of the 22 patients (86%) without need for an open diagnostic procedure. In 1 patient, histoplasmosis was suspected from the thoracoscopic biopsy, but open thoracotomy was needed for confirmation. Of the 19 patients with a positive tissue diagnosis, 3 patients had bronchogenic cysts that were completely resected by thoracoscopy. The mean duration of chest tube drainage was 2.3 +/- 0.2 days, and there were no complications or procedure-related deaths. The average length of hospitalization was 6.0 +/- 0.8 days. We believe that thoracoscopy is a safe, rapid, and effective modality for the diagnosis of mediastinal masses. Accurate tissue diagnoses are obtained in most patients without the need for additional procedures. In addition, we have demonstrated that complete excision of certain benign lesions during thoracoscopy is possible.

Adolescent↗
PubMed1993

Thoracoscopy in the management of empyema in children.

Many pediatric surgeons advocate early open drainage or decortication for children with acute empyema. Unfortunately, such procedures can be associated with significant morbidity. Since 1981, we have used early thoracoscopic adhesiolysis and pleural debridement as an alternative to open thoracotomy in 9 children with acute empyema. The average age was 7.8 +/- 1.8 years (range, 2 to 16). All patients had failed initial treatment, which included antibiotics and chest tube drainage. All procedures were performed under general anesthesia. Following thoracoscopy, 8 of the 9 patients were managed with a single drainage tube and the average duration of tube drainage was 8.4 +/- 1.4 days. One patient died of underlying leukemia. Of the 8 patients who recovered, the average postoperative hospital stay was 13.4 +/- 2.9 days. No complications resulted from the thoracoscopies and there was no need for further surgical intervention in any of these patients. We conclude that thoracoscopy allows for minimally invasive, yet effective treatment of acute empyema with loculated collections. Thoracoscopic visualization of the pleural cavity permits efficient debridement, thorough adhesiolysis, and optimal placement of drainage tubes. Since we have begun using early thoracoscopy in the treatment of pediatric empyema, open drainage or decortication has not been required in any of these patients. Thoracoscopy is a useful adjunct in the treatment of empyema in children and its early application may eliminate the need for decortication.

Chest Tubes↗
PubMed1993

Successful transplantation of marginally acceptable thoracic organs.

OBJECTIVE: This study evaluates the efficacy of personally inspecting marginal thoracic organ donors to expand the donor pool. SUMMARY BACKGROUND DATA: The present donor criteria for heart and lung transplantation are very strict and result in exclusion of many potential thoracic organ donors. Due to a limited donor pool, 20-30% of patients die waiting for transplantation. METHODS: The authors have performed a prospective study of personally inspecting marginal donor organs that previously would have been rejected by standard donor criteria. RESULTS: Fourteen marginal hearts and eleven marginal lungs were inspected. All 14 marginal hearts and 10 of the marginal lungs were transplanted. All cardiac transplant patients did well. The mean ejection fraction of the donor hearts preoperatively was 39 +/- 11% (range 15-50%). Postoperatively, the ejection fraction of the donor hearts improved significantly to 55 +/- 3% (p < 0.002). Nine of the ten lung transplant patients did well and were operative survivors. Our donor pool expanded by 36% over the study period. CONCLUSIONS: The present donor criteria for heart and lung transplantation are too strict. Personal inspection of marginal thoracic donor organs will help to maximize donor utilization.

Heart↗
PubMed1993

Thoracoscopic surgery for diseases of the lung and pleura. Effectiveness, changing indications, and limitations.

OBJECTIVE: This study compared the results of video-assisted thoracic surgery (VATS) with thoracoscopic surgery (TS) for diseases of the lung and pleura. SUMMARY BACKGROUND DATA: No studies exist that compare the capabilities of VATS with advanced video systems and instrumentation to that of TS which has been done for 80 years. METHODS: A retrospective study was done comparing the effectiveness, indications, complications, and limitations of TS and VATS done for four categories of pleural disease: 1) pleural fluid problems, 2) diffuse lung disease, 3) lung masses, and 4) pneumothorax. The TS period was 1981-1990. The VATS period was 1991-1992. RESULTS: Eighty-nine consecutive TS cases and 64 consecutive VATS cases were reviewed. TS for resolution of pleural fluid problem was successful in 29 of 34 patients (85%), and VATS was successful in 18 of 20 (90%). Diffuse lung disease was diagnosed by TS using a cup biopsy on end-stage patients in respiratory failure. Since 1991 the diagnosis has been made with VATS using stapled wedge excisions on ambulatory patients. Surgical mortality decreased from 33% (10 of 30) to 9% (1 of 11) and the postoperative stay from 16.6 +/- 2.4 days to 8.2 +/- 2.2 days. Lung masses were diagnosed entirely by incisional biopsies using TS. Diagnosis was made in 83% and postoperative stay was 5.3 +/- 1.0 day. VATS allowed excisional biopsies permitting diagnosis in 100% with a postoperative stay of 3.0 +/- 0.2 days (p = 0.05). However, 20% required conversion to thoracotomy to locate the subpleural mass. TS was performed for spontaneous pneumothorax in only 26% (5 of 19) of the total pneumothorax cases, whereas, VATS was used for spontaneous pneumothorax in 67% (12 of 18). CONCLUSION: VATS has continued the effectiveness of TS for treating pleural fluid problems, has resulted in earlier surgical diagnostic intervention in diffuse lung disease and earlier therapeutic intervention in primary pneumothorax states, and has markedly expanded the safety, efficacy and indications for lung mass biopsy.

Adolescent↗
PubMed1993

Heat stress regulates the human 70-kDa heat-shock gene through the 3'-untranslated region.

Cells respond to a variety of stresses by synthesizing a family of proteins termed heat-shock proteins (HSP). Recently, the 3'-untranslated regions (UTRs) of some mRNAs have been shown to be important in the posttranscriptional regulation of protein production. Therefore, we hypothesized that heat could regulate HSP70 production through the HSP70 3'-UTR, in addition to its known effects on transcription. To test this hypothesis, cells were transfected with either a plasmid containing sequences encoding the human HSP70 or beta-globin 3'-untranslated region placed downstream of a chloramphenicol acetyltransferase (CAT) reporter gene. In both plasmids, the CAT gene was driven by an SV40 promoter. Following heat stress, cells transfected with the CAT construct containing the HSP70 3'-UTR showed increased CAT activity relative to the beta-globin 3'-UTR construct. This effect paralleled increases in HSP70 mRNA and levels of the inducible HSP70 protein by Western blot. These studies identify a heat-induced mechanism of posttranscriptional control of HSP70 synthesis utilizing the HSP70 3'-UTR, which may be important in the cells ability to regulate the heat-shock response.

Base Sequence↗
PubMed1993

Inhibition of human lung cancer cell line growth by an anti-p185HER2 antibody.

p185HER2, the product of the c-erbB-2 or HER2 gene, is a membrane-bound tyrosine kinase that has structural similarity to the epidermal growth factor receptor. Functionally, interaction of HER2 with its ligand or p185HER2 antibodies affects the growth and differentiation of HER2-expressing breast cancer cell lines. As p185HER2 is also expressed in human lung cancers and human lung cancer cell lines, we hypothesized that these cell lines would also respond to p185HER2 antibodies. To test this hypothesis, we cultured human non-small cell lung cancer cell lines in the presence of a p185HER2 monoclonal antibody called 4D5. 4D5 inhibited the growth of p185HER2-expressing cell lines in a dose-dependent fashion. In addition, BEAS.2B, a p185HER2-nonexpressing bronchial epithelial cell line, was transfected with the HER2 cDNA, resulting in high-level p185HER2 expression, and growth of BEAS.HER2 was now inhibited by 4D5 exposure. Mechanistically, 4D5 appeared to have a weak agonist effect on the tyrosine kinase function of p185HER2, as exposure of p185HER2-expressing cell lines to 4D5 resulted in increased p185HER2 phosphorylation. Furthermore, inhibition of tyrosine kinase function with Genistein reversed the 4D5-induced growth inhibition. Therefore, 4D5 can regulate the growth of p185HER2-expressing lung cancer cell lines through agonist effects on p185HER2.

Adenocarcinoma↗
PubMed1993

Oncogenes and growth factors in human lung cancer.

We are only beginning to understand the importance of lung cancer tumor biology in relation to prognosis and response to therapy. Many of the biologic and genetic changes we have described are preliminary observations and require further confirmation before clinical use. However, information concerning three oncogenes may soon prove to be helpful in the clinical arena: the myc genes in SCLC, and the ras genes and c-erbB-2 in NSCLC. In general their presence identifies poor patient response to therapy and poor survival. These markers are currently being used in a clinical setting at some research centers, but are not recommended for general diagnostic or prognostic use without further confirmation of their utility. Incorporation of this information with that learned by standard staging procedures may result in improved understanding of patient prognosis and challenge current concepts of lung cancer treatment. For example, surgically resected stage I NSCLC patients may benefit from adjuvant therapy if found to have these adverse biologic factors, and require more stringent follow-up after therapy. Finally the understanding of the pathogenesis of lung cancer may enable the development of novel therapy directed against these growth pathways. Our ultimate goal is to derive a therapeutic and prognostic paradigm involving both molecular-genetic and clinical factors to arrive at an optimal staging model and treatment plan.

Female↗
PubMed1992

Effect of amplification of dhfr and lac Z genes on growth and beta-galactosidase expression in suspension cultures of recombinant CHO cells.

Studies were conducted to characterize the effect of gene amplification and foreign gene expression on recombinant CHO cell growth. Chinese hamster ovary (CHO) cells were transfected with an expression vector containing the gene for dihydrofolate reductase (dhfr) and the gene for human beta-interferon (beta-IFN) or the lac Z gene which codes for beta-galactosidase (beta-gal). The recombinant genes in these CHO cells were amplified stepwise by growth in 0, 10(-7), and 10(-6) M methotrexate (MTX), and the beta-gal expressing cells were adapted to suspension culture. Flow cytometric methods (FCM) were used to measure the distribution of amplified dhfr gene content and foreign beta-gal gene expression in the cell populations. A biochemical assay for beta-gal was also used. Beta-gal expression was found to increase with increasing gene amplification. The growth rate of recombinant CHO cells at 10(-7) M MTX was found to be 20% lower than that of recombinant CHO cells in MTX-free medium, and the cell growth rate at 10(-6) M MTX was 20% lower than that of recombinant CHO cells at 10(-7) M MTX. There was no effect of 10(-5) M MTX on the growth of CHO-DG44 (dhfr-) cells. The reduction of growth rate in recombinant CHO cells is therefore thought to be mainly due to the effect of dhfr and foreign gene amplification and increased beta-galactosidase expression.

Animals↗
PubMed1992

Reduced-size porcine lung transplantation: long-term studies of pulmonary vascular resistance.

The use of isolated adult lobes for pediatric lung transplantation has recently been reported and could potentially help alleviate the profound pediatric donor lung shortage. However, the effect of chronic denervation on pulmonary vasculature of isolated mature lobar transplants is not well understood. Previously, we reported that chronic denervation of the immature porcine lobe results in abnormal pulmonary vascular compliance. We now present studies of long-term pulmonary hemodynamics in young pigs 12 weeks after transplantation of a reduced-size mature left lower lobe. Resting pulmonary vascular resistance of the transplanted mature lobes was similar to that of innervated lobes of age-matched controls. In addition, pulmonary vascular resistance of the transplanted mature lobes did not rise abnormally in response to increased flow caused by clamping the contralateral pulmonary artery. We conclude that denervation of the mature porcine lobe does not result in abnormal pulmonary vascular resistance. In addition, vascular compliance of reduced-size mature porcine lobar transplants is superior to that of denervated reimplanted immature lobes. These findings suggest a deleterious effect of denervation on pulmonary vascular development of the growing porcine lung.

Animals↗
PubMed1992

Does a posterior aneurysm increase the risk of endocardial resection?

The bias has been that the ideal anatomic circumstance for endocardial resection is the anterior left ventricular location. Posterior left ventricular aneurysms have been thought to be problematic to map and more difficult to close, and possibly to have a different substrate for ventricular tachycardia. To address this problem, we retrospectively reviewed the cases of 110 consecutive patients who underwent sequential endocardial resection for ventricular tachycardia between 1983 and 1991. Ninety-six patients had an anterior aneurysm, and 14 patients had a posterior aneurysm or infarct. Operative survival and 5-year survival were very similar between the two groups (p = not significant). A positive postoperative electrophysiological study was present in 11% of the anterior group versus 14% of the posterior group (p = not significant). There was a significantly greater incidence of mitral valve replacement in the posterior group, and we believe this was most likely due to frequent localization of the arrhythmia to the papillary muscle. Otherwise, patients with a posterior aneurysm or infarct had surgical results equivalent to those in patients with an anterior location. As long as there is a discrete aneurysm or infarct, endocardial resection is a safe and effective therapeutic procedure for ventricular tachycardia.

Endocardium↗
PubMed1992

Mechanisms of p185HER2 expression in human non-small cell lung cancer cell lines.

To identify mechanisms that allow p185HER2 expression in lung cancer, we performed Western, Southern, and Northern blot analyses of 14 cell lines derived from human non-small cell lung carcinomas and one cell line derived from a human mesothelioma. Human bronchiole epithelial cells and rat type II pneumocytes were found to express p185HER2 at low to undetectable levels by Western blot technique. In contrast, 13 lung cancer cell lines expressed p185HER2, and eight of these 13 expressed p185HER2 at levels at least 2-fold higher than that found in normal bronchiole epithelial cells or type II pneumocytes. Genomic Southern analysis showed that amplification of the HER2 gene was present in only one of the eight cell lines that expressed p185HER2 at these higher levels. Increased levels of steady-state HER2 mRNA occurred in the remaining seven cell lines. We conclude that in human non-small cell lung carcinoma cell lines the most common mechanism resulting in increased p185HER2 expression is due to mechanisms that increase HER2 mRNA levels, with HER2 gene amplification occurring less commonly.

Adenocarcinoma↗