Search PubMed⌕ Search

Biomedical subjects

Larry R Kaiser

Publications and source records attributed to Larry R Kaiser.

62 records · Page 4Linked to original sources
PubMed2002

Sarcomeres are added in series to emphysematous rat diaphragm after lung volume reduction surgery.

STUDY OBJECTIVES: The diaphragm adapts to its shortened state in experimental emphysema primarily by losing sarcomeres in series, thus reducing its optimal operating length. One would expect improved diaphragmatic function after lung volume reduction surgery (LVRS) only if the muscle can readapt to its elevated, lengthened postoperative position by either adding back sarcomeres or lengthening sarcomeres. We used a model of elastase-induced emphysema in rats to test the hypothesis that sarcomere addition occurs following LVRS. DESIGN: A cohort of emphysematous rats was created by the intratracheal instillation of elastase. Five months after the instillation, one group of rats underwent measurement of in situ costal diaphragm length via laparotomy, the determination of optimal muscle fiber operating length (Lo) on stimulated diaphragm strips in vitro, and the measurement of sarcomere length by electron microscopy on strips fixed at Lo. Another group of rats underwent LVRS or sham sternotomy 5 months after the instillation, and 5 months following the operation these animals underwent the same series of diaphragmatic studies. RESULTS: Lo was significantly greater in rats that underwent LVRS than those that underwent sternotomy (mean [+/- SE] Lo after LVRS, 2.50 +/- 0.08 cm; mean Lo after sternotomy, 2.27 +/- 0.06 cm; p = 0.013). There was no significant difference in sarcomere lengths between the two groups (2.95 +/- 0.04 vs 3.04 +/- 0.04 microm, respectively; p = 0.10). Using Lo as the length basis, the mean sarcomere number was calculated to be 8,712 +/- 192 in animals that had undergone LVRS and 7,144 +/- 249 in animals that had undergone sternotomy (p < 0.001). CONCLUSION: Sarcomere length is not significantly altered but sarcomeres are added in series following LVRS in this experimental model of emphysema/LVRS. It is likely that this sarcomere addition is a prerequisite to the improvement in inspiratory muscle function that has been observed following LVRS in humans.

Animals↗
PubMed2002

Suction vs water seal after pulmonary resection: a randomized prospective study.

STUDY OBJECTIVE: To evaluate whether suction or water seal is superior in the management of chest tubes after pulmonary resection. DESIGN: A prospective, randomized, controlled trial. After an initial, brief period of suction, patients were randomized to water seal or - 20 cm H(2)O suction. SETTING: University hospital. PATIENTS: Sixty-eight patients who underwent wedge resection, segmentectomy, or lobectomy were included in the study. Those patients who underwent reoperative surgery or lung volume reduction surgery were excluded. RESULTS: There were 34 patients in each group. The two groups were evenly matched for age, sex, operation performed, severity of lung disease, and nutritional status. Fifteen patients in each group (44%) had an air leak at the completion of surgery. The duration of the air leak was shorter in the water seal group than in the suction group (mean +/- SEM, 1.50 +/- 0.32 days vs 3.27 +/- 0.80 days, respectively; p = 0.05). The mean times to removal of chest tubes were 3.33 +/- 0.35 days in the water seal group and 5.47 +/- 0.98 days in the suction group (p = 0.06). The length of stapled parenchyma was measured for each patient and averaged 24.9 cm for the water seal group and 18.5 cm for the suction group (p = 0.18). When corrected for the length of staple lines, the duration of air leaks and days with chest tube were dramatically lower in the water seal group (p = 0.02 and p = 0.02, respectively). CONCLUSION: Placing chest tubes on water seal after a brief period of suction after pulmonary resection shortens the duration of the air leak and likely decreases the time that the chest tubes remain in place. Adoption of this practice may result in lower morbidity and lower hospital costs.

Aged↗
PubMedDate not supplied

Patterns and predictions of resident misbehavior--a 10-year retrospective look.

BACKGROUND: Surgical educators are charged with ensuring that their trainees conduct themselves in a professional manner. The authors retrospectively reviewed a 10-year experience of incident reports on surgical housestaff to determine patterns and predictors of behavior. METHODS: A retrospective review of all letters, e-mails, and incident reports was conducted for general surgery residents from 1995 to 2005. Descriptive variables were selected for binary categorization (not mutually exclusive): poor professional conduct, protocol violation, administrative deficiency, verbal mistreatment, physical boundary issues, mistreatment of superiors, and deficient medical student interaction. Resident status was defined as current, graduate, and attrition. RESULTS: Of 110 residents [90 [82%] categorical, 23 [21%] undesignated preliminary (3 overlapped both groups); 87 [79%] male, 23 [21%] female] who trained at the University of Pennsylvania during this period, 66 complaints were generated about 29 individuals. Overall, 50 of the 66 complaints (76%) were directed toward men and the remaining 16 (24%) toward women; 24% of all men and 35% of all women received 1 or more complaints. A total of 76% of complaints concerned categorical residents and 24% undesignated preliminary residents. And 26% of all categorical residents and 26% of all preliminary residents received at least 1 complaint. The most common complaints concerned professional conduct (83%), protocol violation (33%), verbal mistreatment (23%), deficiencies of administrative duties (8%), violations of physical boundaries (5%), deficient medical student interaction (5%), and mistreatment of attendings by residents (3%). Recipients of verbal mistreatment included staff nurses (27%), radiology technicians (13%), medical students (13%), environmental services employees (7%), security guards (7%), patients (7%), surgery attendings (7%), anesthesia attendings (7%), internal medicine chief residents (7%), and pharmacists (7%). A total of 31% of the complaints were regarding residents who involuntarily departed and 7% regarding residents who left voluntarily before completion. The mean PGY level at first complaint was 2.2 years. Of the 29 residents receiving complaints, 16 had recurrent offenses (range 2 to 7 total complaints, positive predictive value [PPV] 53%). CONCLUSION: Resident misbehavior manifests early and recurs often. Furthermore, it is frequently directed toward perceived subordinates. Nondesignated preliminary status, premature departure from the program, and the eventual selection of specific subspecialty fellowships seems to increase the risk for resident misbehavior. Identified residents require close surveillance and remediation.

Adult↗
PubMedDate not supplied

Pathological response to preoperative chemoradiation worsens with anemia in non-small cell lung cancer patients.

PURPOSE: Positive links between hemoglobin level and therapeutic tumor response are well documented in carcinoma of the cervix and the head and neck, but little evidence of such a link exists for lung cancer. We analyzed our series of patients treated with preoperative chemoradiation for stage IIIA non-small cell lung carcinoma. PATIENTS AND METHODS: Between June 1992 and February 2000, 41 consecutive patients with clinical stage IIIA (N2, documented by mediastinoscopy or another invasive procedure) non-small cell lung carcinoma received preoperative-intent chemoradiation. The median preoperative radiation dose was 48.6 Gy, and all patients received cisplatin- or paclitaxel-based chemotherapy. Response was graded on a four point scale: (1) progressive disease before surgery and/or technically inoperable; (2) stable disease with resection performed, but specimen containing > 50% viable tumor; (3) partial response with specimen containing < 50% tumor; and (4) complete response or near-complete response: RO resection with no residual carcinoma or pT1NO with only microscopic residual foci. Pretreatment hemoglobin values were correlated with pathological outcome using ANOVA and the non-parametric test for trend across ordered groups. RESULTS: The mean hemoglobin level for groups 1 through 4 was 11.8, 12.1, 12.5, and 13.2 respectively, and the association was statistically significant. If the analysis was limited to patients actually undergoing surgery (eliminating group 1), the association remained significant. The nonparametric test for trend across ordered groups was also significant with and without group 1. DISCUSSION: Our analysis supports the hypothesis that response to chemoradiation of non-small cell lung carcinoma improves with increasing hemoglobin levels.

Adult↗
PubMedDate not supplied

Alterations in cell cycle genes in early stage lung adenocarcinoma identified by expression profiling.

In normal lung epithelial cells, cellular division is an ordered, tightly regulated process involving multiple checkpoints that assess extracellular growth signals, cell size, and DNA integrity. In contrast, neoplastic lung cells develop the ability to bypass several of these checkpoints, particularly at the G1/S and G2/M boundaries. We used genomic profiling to compare gene expression levels in early stage lung adenocarcinomas and non-neoplastic pulmonary tissue in order to comprehensively identify alterations in the process of cell cycling. RNA extracted from node negative, poorly differentiated lung adenocarcinomas (15 patients) and non-neoplastic pulmonary tissue (5 patients) was hybridized to oligonu-cleotide microarray filters containing 44,363 genes. Ontological classification was used to extract genes involved with cell cycle progression. Further analysis discovered a subset of differentially expressed genes for further study. Of the 624 cell cycle genes on the microarray filters, 40 genes were predicted to be differentially expressed in lung adeno-carcinomas. Alterations in several genes (i.e., cyclin B1, cyclin D1, p21, MDM2) are consistent with published data in the literature. We also identified 19 novel genes that have neither been described in non-small cell lung cancer (i.e., cdc2, cullin 4A, ZAC, p57, DP-1, GADD45, PISSLRE, cdc20) nor in any other tumors (i.e., cyclin F, cullin 5, p34). These results identified several potential cell cycle genes altered in lung cancer.

Adenocarcinoma↗
PubMedDate not supplied

Microarray data simulator for improved selection of differentially expressed genes.

The development of microarray technology has allowed researchers to measure expression levels of thousands of genes simultaneously. Analysis of these data requires the best normalization and statistical approaches to account for the biological and technical variability inherent in the technique. To approach this problem we have developed a publicly available simulator of microarray hybridization experiments that can be used to help assess the accuracy of bioinformatic tools in discovering significant genes. After analyzing microarray hybridization experiments from over 50 samples, an estimate of various degrees of technical and biological variability was obtained. This information was used to develop a simulator of microarray hybridization data which modeled "normal tissue samples" and "diseased tissue samples" with known, defined, changes in gene expression (a "gold standard"). The data derived from the simulator were then used to evaluate the true positive and false negative rates of several normalization procedures and gene selection techniques. We found that the type of normalization approach used was an important aspect of data analysis. Global normalization was the least accurate approach. Evaluation of gene selection techniques showed that "Significance analysis of microarrays" (SAM) and "Patterns of Gene Expression" (PaGE) were more accurate than simple t-test analysis. We provide access to the microarray hybridization simulator as a public resource for biologists to further test new emerging genomic bioinfomatic tools.

Computer Simulation↗
PubMedDate not supplied

Differentially expressed apoptotic genes in early stage lung adenocarcinoma predicted by expression profiling.

OBJECTIVE: In undiseased lung epithelial cells, apoptosis is an evolutionarily conserved and genetically regulated form of cell suicide which plays an important role in development and in the maintenance of tissue homeostasis. Neoplastic lung cells develop the ability to deregulate growth by alterations in these genes which control apoptosis. Genomic profiling was used to compare gene expression levels in early stage lung adenocarcinomas and nonneoplastic pulmonary tissue in order to comprehensively identify alterations in the process of apoptosis. METHODS: RNA extracted from node negative, poorly differentiated lung adenocarcinomas (15 patients) and nonneoplastic pulmonary tissue (5 patients) was hybridized to oligonucleotide microarray filters containing 44,363 genes. Ontological classification was used to extract genes involved with apoptosis. Further analysis discovered a subset of differentially expressed genes for further study. RESULTS: Of the 308 apoptotic genes on the microarray filters, 24 genes were predicted to be differentially expressed in lung adenocarcinomas. Alterations in several genes (i.e., Akt, BcL-xL, PTEN, FAS) are consistent with the literature. We also identified 10 novel genes that have not been described in nonsmall cell lung cancer (i.e., RIP, Caspase 1, PDK-1). CONCLUSIONS: These results identified several potential apoptotic genes altered in lung cancer.

Adenocarcinoma↗