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Biomedical subjects

D H Johnson

Publications and source records attributed to D H Johnson.

At least 55 records · Page 3Linked to original sources
PubMed2000

Schlemm's canal becomes smaller after successful filtration surgery.

OBJECTIVE: To determine whether filtration surgery causes secondary changes in the trabecular meshwork and Schlemm's canal. Successful filtration surgery allows most aqueous outflow to enter the filtration bleb, bypassing the meshwork and canal, and may result in underperfusion of these structures. METHODS: Eyes with primary open-angle glaucoma (POAG) that had undergone filtration surgery were studied and compared with eyes with POAG that had not undergone surgery. In addition, normal eyes and eyes with pseudoexfoliative glaucoma were studied for comparison. The trabecular meshwork and Schlemm's canal were examined by light and electron microscopy. RESULTS: Schlemm's canal was significantly smaller in eyes with POAG after filtration surgery than in normal eyes (canal width, 178 +/- 71 microm vs 276 +/- 52 microm; P<.001) or in eyes with medically treated POAG of similar clinical severity (261 +/- 60 microm, P =. 03). The decrease in canal size seemed to be related to the success of the filtration procedure, since eyes with blebs and low pressures had the smallest canals. Eyes with medically treated POAG at earlier clinical stages of glaucoma did not have a significant decrease in canal size when compared with normal eyes. Eyes with advanced pseudoexfoliative glaucoma had canal widths 20% smaller than those in normal eyes (P =.08). CONCLUSIONS: Filtration surgery was associated with a decrease in the size of Schlemm's canal, most likely due to underperfusion of the meshwork. A significant decrease in canal size is otherwise not a finding in POAG. In contrast, the canal tended to become smaller in advanced cases of pseudoexfoliative glaucoma. CLINICAL RELEVANCE: The decrease in size of Schlemm's canal after successful filtration surgery could make glaucoma more difficult to control if the filter ultimately fails. Arch Ophthalmol. 2000;118:1251-1256

Aged↗
PubMed2000

Mediastinal lymph node dissection improves survival in patients with stages II and IIIa non-small cell lung cancer. Eastern Cooperative Oncology Group.

BACKGROUND: Mediastinal lymph node dissection (MLND) is an integral part of surgery for non-small cell lung cancer (NSCLC). To compare the impact of systematic sampling (SS) and complete MLND on the identification of mediastinal lymph node metastases and patient survival, the Eastern Cooperative Oncology Group (ECOG) stratified patients by type of MLND before participation in ECOG 3590 (a randomized prospective trial of adjuvant therapy in patients with completely resected stages II and IIIa NSCLC). METHODS: Eligibility requirements for study entry included a thorough investigation of the mediastinal lymph nodes with either SS or complete MLND. The former was defined as removal of at least one lymph node at levels 4, 7, and 10 during a right thoracotomy and at levels 5 and/or 6 and 7 during a left thoracotomy, while the latter required complete removal of all lymph nodes at those levels. RESULTS: Three hundred seventy-three eligible patients were accrued to the study. Among the 187 patients who underwent SS, N1 disease was identified in 40% and N2 disease in 60%. This was not significantly different than the 41% of N1 disease and 59% of N2 disease found among the 186 patients who underwent complete MLND. Among the 222 patients with N2 metastases, multiple levels of N2 disease were documented in 30% of patients who underwent complete MLND and in 12% of patients who had SS (p = 0.001). Median survival was 57.5 months for those patients who had undergone complete MLND and 29.2 months for those patients who had SS (p = 0.004). However, the survival advantage was limited to patients with right lung tumors (66.4 months vs 24.5 months, p<0.001). CONCLUSIONS: In this nonrandomized comparison, SS was as efficacious as complete MLND in staging patients with NSCLC. However, complete MLND identified significantly more levels of N2 disease. Furthermore, complete MLND was associated with improved survival with right NSCLC when compared with SS.

Carcinoma, Non-Small-Cell Lung↗
PubMed2000

Induction chemotherapy before surgery for early-stage lung cancer: A novel approach. Bimodality Lung Oncology Team.

OBJECTIVE: This phase II trial assessed the feasibility, as measured by response rate, toxicity, resectability rate, and surgical morbidity and mortality rates, of perioperative paclitaxel and carboplatin chemotherapy in patients with early-stage non-small cell lung carcinoma. METHODS: All patients required negative mediastinoscopy results and adequate medical parameters to undergo induction chemotherapy and an operation. Superior sulcus patients were excluded. Chemotherapy consisted of paclitaxel 225 mg/m(2) over 3 hours and carboplatin (area under the curve = 6) every 21 days for 2 cycles preoperatively. Three postoperative cycles of chemotherapy were planned for patients undergoing complete resection. RESULTS: Between June 1996 and July 1998, 94 patients were entered into the study. Sixty-five (69%) were men, and the median age was 64 years (range, 34-79 years). After induction chemotherapy, 53 of 94 (56%; 95% confidence interval, 46%-67%) had a major objective response, 88 (94%) underwent surgical exploration, and 81 (86%; 95% confidence interval, 78%-92%) underwent complete resection. Reasons for not undergoing an operation included disease progression (n = 3), clinically unresectable status (n = 1), death (n = 1), and patient lost to follow-up (n = 1). Two postoperative deaths occurred. Six (6%; 95% confidence interval, 0%-13%) pathologic complete responses were observed. Ninety (96%) patients received the planned preoperative chemotherapy versus 45% receiving postoperative chemotherapy. No unexpected chemotherapy or surgical morbidity occurred. The 1-year survival is currently estimated at 85%, and the median survival has not yet been reached. CONCLUSIONS: Induction chemotherapy with paclitaxel and carboplatin is feasible and produces a high response rate with acceptable morbidity and mortality rates in early-stage non-small cell lung carcinoma. A prospective randomized trial comparing 3 cycles of induction chemotherapy and surgery with surgery alone in early-stage non-small cell lung carcinoma is planned.

Adult↗
PubMed2000

Locally advanced, unresectable non-small cell lung cancer: new treatment strategies.

Approximately 40% of non-small cell lung cancer (NSCLC) patients present with locally advanced, unresectable lesions. Treatment with thoracic radiotherapy yields survivals averaging just 9 to 10 months, and long-term survival at 5 years is poor. Recent studies indicate that chemotherapy followed by thoracic radiotherapy improves 5-year survival by three- to fourfold. Nevertheless, most patients do ultimately die of the underlying disease. New strategies designed to enhance local tumor control-use of radiation-sensitizing drugs, three-dimensional treatment planning techniques, or altered radiation fractionation schedules-may further improve survival outcome. In addition, newer cisplatin-based regimens containing either paclitaxel or vinorelbine improve survival over that achieved with older vinca alkaloid or podophyllotoxin combination regimens. Accordingly, the newer drug regimens combined with radiotherapy can be expected to further improve survival in this subset of NSCLC patients. Prospective studies are underway to test this conjecture.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2000

Evolution of cisplatin-based chemotherapy in non-small cell lung cancer: a historical perspective and the eastern cooperative oncology group experience.

Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related death in most industrialized nations, including the United States. Frequently, patients with unresectable disease are treated with symptomatic care alone or, in the case of locally advanced, unresectable lesions, with radiotherapy alone. In general, chemotherapy is viewed as ineffective, and therefore rarely recommended except by medical oncologists. Over the past 2 decades, however, it has become clear that chemotherapy, and in particular cisplatin-based chemotherapy, provides a modest survival advantage. In addition, recent studies indicate that chemotherapy can improve tumor-related symptoms and quality of life. With modern chemotherapy, median survival averages around 9 to 10 months in advanced NSCLC, a figure comparable to that achieved with treatment of extensive-stage small cell lung cancer, a malignancy generally viewed as chemotherapy sensitive. Importantly, existing data indicate that chemotherapy is also cost-effective. Given these observations, it is appropriate today for patients with advanced NSCLC to receive chemotherapy.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2000

Impact of cancer-related fatigue on the lives of patients: new findings from the Fatigue Coalition.

PURPOSE: This survey was designed to confirm the prevalence and duration of fatigue in the cancer population and to assess its physical, mental, social, and economic impacts on the lives of patients and caregivers. Patients and Methods. A 25-minute telephone interview was completed with 379 cancer patients having a prior history of chemotherapy. Patients were recruited from a sample of 6, 125 households in the United States identified as having a member with cancer. The median patient age was 62 years, and 79% of respondents were women. Patients reporting fatigue at least a few times a month were asked a series of questions to better describe their fatigue and its impact on quality of life. RESULTS: Seventy-six percent of patients experienced fatigue at least a few days each month during their most recent chemotherapy; 30% experienced fatigue on a daily basis. Ninety-one percent of those who experienced fatigue reported that it prevented a "normal" life, and 88% indicated that fatigue caused an alteration in their daily routine. Fatigue made it more difficult to participate in social activities and perform typical cognitive tasks. Of the 177 patients who were employed, 75% changed their employment status as a result of fatigue. Furthermore, 65% of patients indicated that their fatigue resulted in their caregivers taking at least one day (mean, 4.5 days) off work in a typical month. Physicians were the health care professionals most commonly consulted (79%) to discuss fatigue. Bed rest/ relaxation was the most common treatment recommendation (37%); 40% of patients were not offered any recommendations. CONCLUSIONS: Cancer-related fatigue is common among cancer patients who have received chemotherapy and results in substantial adverse physical, psychosocial, and economic consequences for both patients and caregivers. Given the impact of fatigue, treatment options should be routinely considered in the care of patients with cancer.

Adult↗
PubMed2000

Treatment and outcomes for elderly patients with small cell lung cancer.

It is estimated that approximately half of the 500 000 people diagnosed with lung cancer worldwide every year are aged >70 years. Thus, this disease represents a major problem in the elderly and one that will indeed increase as the median age of the population increases. For small cell lung cancer (SCLC), which accounts for approximately 20% of cases of lung cancer, the primary treatment is chemotherapy and in the majority of cases the primary aim is to control the disease which generally would have spread beyond the lungs at the time of presentation. A small number of 'standard' chemotherapy regimens (combined with radiotherapy for patients with limited disease) have been shown to improve survival and quality of life and are widely used. Much of the work investigating the relationship between age and treatment outcomes has been based on clinical trial data and may itself be inherently biased due to trial eligibility criteria excluding elderly patients. However, there is no good evidence that elderly patients fare worse with treatment than their younger counterparts in terms of response rates and survival. Nevertheless with increasing age comes increasing concomitant illnesses which may account for the widely observed increases in drug toxicity, and this may be the primary consideration in selecting the treatment option. Thus for many elderly patients, carboplatin/ etoposide may be the treatment of choice because it is perhaps the least toxic of the standard regimens. Whatever regimen is chosen, the key to treatment effectiveness seems to be to deliver the first 3 or 4 cycles without delay or dosage reduction. Although palliation of symptoms remains a major goal in the treatment of all patients with SCLC there is a dearth of data on whether elderly patients are equally well palliated as their younger counterparts. There is no good evidence that age per se should be a factor in deciding whether patients should receive standard treatment rather than a more gentle approach, and more elderly patients should be included in clinical trials. The key areas where more information is required regarding the treatment and outcomes of elderly patients with SCLC are the assessment of palliation, and comprehensive reviews of all patients diagnosed with the disease, not just those included in trials.

Aged↗
PubMed2000

Paclitaxel, 5-fluorouracil, and leucovorin (TFL) in the treatment of metastatic breast cancer.

To assess the activity of paclitaxel in combination with 5-fluorouracil (5-FU) and leucovorin in breast cancer, a phase II trial was conducted in women with metastatic disease. Toxicity, response rate, median survival, median duration of response, and median time to disease progression were measured. Between January 1994 and May 1996, 47 patients with metastatic breast cancer and an Eastern Cooperative Oncology Group (ECOG) performance status (PS) < or = 2 who had previously been treated with chemotherapy received 175 mg/m2 paclitaxel over 3 hours on day 1. After paclitaxel administration, 300 mg intravenous (i.v.) leucovorin over 30 minutes was administered followed by 350 mg/m2 i.v. push 5-FU. Both 5-FU and leucovorin were given on days 1-3. Treatment was repeated every 28 days for a minimum of 6 cycles per patient. Two (4%) patients had a complete response and 21 (45%) patients had a partial response for an overall response rate of 49% (95% confidence interval: 35%-63%). The median survival was 17.7 months, median duration of response was 8.6 months, and median time to disease progression was 6.3 months. There was no statistical difference in survival or time to progression between anthracycline-naive, anthracycline-sensitive, and anthracycline-resistant patients. Nine (19%) patients had grade 3 or 4 neutropenia, and no patient required blood or platelet transfusion. The most frequently observed nonhematologic toxicities were arthralgia and myalgia. Pharmacokinetic data were obtained on 19 patients. Responders had higher peak plasma concentrations of paclitaxel than nonresponders (4.46 vs. 2.9 micrograms/mL; P = 0.02). Paclitaxel/5-fluorouracil/leucovorin is an active, well-tolerated regimen for patients with metastatic breast cancer.

Adult↗
PubMed2000

A phase I trial of outpatient weekly docetaxel and concurrent radiation therapy for stage III unresectable non small-cell lung cancer: a Vanderbilt Cancer Center Affiliate Network (VCCAN) Trial.

Docetaxel has demonstrated activity as a radiosensitizer in numerous preclinical studies, probably due to its role as a cell cycle synchronizer for the G2/M radiosensitive phase of the cell cycle. We conducted a phase I trial to determine the maximum-tolerated dose (MTD) and dose-limiting toxicities (DLT) of docetaxel with concurrent thoracic radiation therapy (TRT) to patients with unresectable stage III non small-cell lung cancer (NSCLC). Fifteen patients were entered into this study. Docetaxel was administered as a 1-hour intravenous (I.V.) infusion, repeated every week for 6 weeks with starting dose of 20 mg/m2. Doses were escalated in 10 mg/m2 increments in successive cohorts of three new patients, if tolerated. Unacceptable toxicity was defined as grade = 3 nonhematologic or hematologic toxicity according to Eastern Cooperative Oncology Group (ECOG) toxicity criteria. TRT was administered to the primary tumor and regional lymph nodes (40 Gy) followed by a boost to the tumor (20 Gy). At the first dose level (20 mg/m2/week), one patient developed grade 4 hyperglycemia and accrual was expanded to five patients. At the second level (30 mg/m2/week), two out of six patients developed grade 3 esophagitis. At the third level (40 mg/m2/week), two out of four patients developed grade 3 esophagitis and one patient developed grade 3 pulmonary toxicity. The weekly docetaxel MTD with concurrent radiation therapy (RT) was found to be 30 mg/m2. The DLT was esophagitis and pulmonary toxicity. Other toxicities encountered included skin reaction, nausea and vomiting, as well as diarrhea. Additionally, there were no treatment-related mortalities or late-occurring toxicities. Esophagitis was the principal DLT of concurrent weekly docetaxel and thoracic radiation in the outpatient setting. The MTD of concurrent weekly docetaxel with TRT is 30 mg/m2 weekly for 6 weeks. This study is still open to accrual with weekly docetaxel and TRT in locally advanced NSCLC patients.

Journal Article↗
PubMed2000

mRNA in situ hybridization of TIGR/MYOC in human trabecular meshwork.

PURPOSE: To determine the distribution of mRNA expression of the trabecular meshwork-induced glucocorticoid response protein/myocilin (TIGR/MYOC) in human trabecular meshwork. METHODS: In situ hybridization using a 1.25-kb probe obtained from reverse transcription-polymerase chain reaction of TIGR/MYOC cDNA was performed to determine the location of cell labeling within the different regions of the meshwork. The effect of dexamethasone on the pattern of labeling was studied in organ cultured meshwork. Trabecular meshwork from three sources was studied: enucleated eyes obtained at autopsy, trabeculectomy specimens obtained during filtration surgery, and meshworks from anterior segments in perfusion organ culture. Hybridization was performed on frozen sections, paraffin sections, and sections from JB-4 plastic-embedded tissue. RESULTS: Labeling for TIGR/MYOC mRNA was present in most trabecular cells of the uveal, corneoscleral, and juxtacanalicular regions but only variably present in the endothelial cells of Schlemm's canal. A similar pattern was found in the trabeculectomy specimens from eyes with primary open-angle or pseudoexfoliative glaucoma. Dexamethasone treatment increased the labeling intensity and number of labeled cells in meshwork, and also the number of labeled endothelial cells of Schlemm's canal. Fresh tissue processed within 12 hours postmortem gave more consistent labeling than older tissue, although some label was found up to 48 hours postmortem. Labeling was found in tissue from all three sources, and with all three embedding techniques; JB-4 sections provided the best morphologic resolution. CONCLUSIONS: In situ hybridization reveals that mRNA expression for TIGR/MYOC is present in most cells in all regions of the meshwork but only variably present in the endothelial cells of Schlemm's canal. Dexamethasone treatment increased the number and intensity of labeled cells, and also increased the number of labeled cells in the endothelial lining of Schlemm's canal.

Aged↗
PubMed2000

Myocilin and glaucoma: A TIGR by the tail?

In 1997, Stone and 14 colleagues from 7 laboratories reported the identification of a gene (TIGR) associated with juvenile open-angle glaucoma (JOAG). Screening of adults with primary open-angle glaucoma (POAG) revealed that about 4% also carried a mutation of the coding region of this gene. The mutations were found through genetic linkage analysis of families with JOAG. Juvenile open-angle glaucoma was a logical starting point in the search for genetic causes of open-angle glaucoma: it shows a strong autosomal-dominant inheritance pattern, occurs at an early age, demonstrates obvious phenotypic signs (dramatic elevation of intraocular pressure and subsequent optic nerve damage), and is likely to be found in multiple generations as parents of affected children are still living. These factors, however, also serve to distinguish it from adult-onset POAG, which generally has a lower intraocular pressure and a less severe course. The discovery of the actual gene represented a true advance over previous studies that had mapped the gene to a segment of a chromosome but did not identify the specific gene. How the mutant gene causes glaucoma is unknown and is the subject of intense research. To date, 26 mutations in the TIGR gene sequence (the term TIGR has been replaced by the term myocilin, abbreviated MYOC) have been described, all associated with either JOAG or adult-onset POAG. A correlation between specific mutations in MYOC and the clinical course of glaucoma has been found. Not all cases of JOAG or POAG have mutations in the MYOC gene, however, indicating that more discoveries of other genes are yet to come. Arch Ophthalmol. 2000;118:974-978

Adult↗
PubMed2000

Giant vacuoles are found preferentially near collector channels.

PURPOSE: To determine whether giant vacuoles form preferentially near collector channels or over regions of optically empty space within the juxtacanalicular tissue (JCT). METHODS: To assess the relationship between giant vacuoles and collector channels, six eyes were perfused with phosphate-buffered saline (PBS) at 20 mm Hg and then fixed by perfusion. Serial sections were cut in the frontal plane and light microscopy used to count the number of giant vacuoles per length of Schlemm's canal. The number of giant vacuoles between two adjacent collector channels was determined. To assess the relationship between giant vacuoles and the ultrastructure of the JCT, an additional seven eyes were perfused with PBS at 10 mm Hg, fixed by perfusion, and examined by transmission electron microscopy. The ultrastructural components of the JCT were quantitated with an image analysis system. RESULTS: Twice as many giant vacuoles were present in regions underlying collector channels as in regions between channels (giant vacuoles per histologic section: 14.0 +/- 1.7 versus 7.3 +/- 0.8, P: = 0.01). Giant vacuoles occurred on both the inner and outer walls of the canal but were more numerous on the inner wall (9.1 +/- 1.0 versus 2.6 +/- 0.4, P: < 0.001). No significant increase in optically empty space was found in the JCT regions underlying giant vacuoles compared with regions with no vacuoles (50.7% +/- 2.3% versus 47.3% +/- 2.5%, P: = 0.09). Examination of the amount of optically empty space immediately adjacent (within 1 microm) to the inner wall endothelial cells of the canal did not reveal a significant difference between regions under vacuoles and regions without giant vacuoles. CONCLUSIONS: Giant vacuoles are found preferentially near collector channels, indicating that aqueous flow across the inner wall is sensitive to downstream pressure. The variability in giant vacuole distribution noted in previous studies is in part due to the distance of the vacuoles from the collector channels. No distinct findings in the JCT were associated with the presence of giant vacuoles.

Aged↗
PubMed2000

Weekly irinotecan and concurrent radiation therapy for stage III unresectable NSCLC.

In preclinical studies, the topoisomerase I inhibitor irinotecan (Camptosar, CPT-11) has demonstrated activity as a radiosensitizer, probably due to its ability to inhibit potentially lethal radiation damage repair. We conducted a phase I trial to determine the maximum-tolerated dose (MTD) and dose-limiting toxicities (DLT) of weekly irinotecan with concurrent thoracic radiation therapy for patients with unresectable stage III non-small-cell lung cancer. For this study, 13 patients received three dose escalations (from 30 to 40 to 50 mg/m2/wk). At the first dose level, one patient developed grade 5 esophagitis. Accrual was expanded to seven patients. None of the remaining six patients developed esophagitis. At the second dose level (40 mg/m2/wk), the worst toxicity, which developed in one patient, was grade 2 esophagitis. At the third dose level (50 mg/m2/wk), two of three patients developed grade 4 nausea and vomiting; grade 3 or 4 esophagitis also occurred in two patients. Of the 12 evaluable patients, seven achieved a partial response, for an overall response rate of 58%. In conclusion, nausea, vomiting, and esophagitis appear to be the principal DLTs of concurrent weekly irinotecan and thoracic radiation in the outpatient setting. The MTD of concurrent weekly irinotecan with thoracic radiation therapy appears to be 40 mg/m2 weekly for 6 weeks. To confirm the MTD of this combination, this study is still open to accrual at the second dose level (40 mg/m2) in combination with carboplatin.

Antineoplastic Agents, Phytogenic↗
PubMed2000

Inhaler technique of outpatients in the home.

OBJECTIVE: Assess the role of evaluation, instruction, and use of spacers by patients using metered dose inhalers (MDIs) in the home. PATIENTS AND SETTING: Patients (age 64 +/- 15 y [mean +/- standard deviation]) receiving home visits by respiratory care practitioners for oxygen therapy had their inhaler technique checked. INTERVENTIONS AND MEASUREMENTS: A detailed acceptable/unacceptable check-off list was used with 172 patients to evaluate inhaler technique. Patients with poor technique were given instruction and their technique was reassessed. A subgroup of 43 patients was reevaluated on up to 3 visits. RESULTS: Only 18% of patients using MDIs without spacers were rated acceptable with the detailed check list. Instruction improved inhaler technique, but few patients with initially poor technique without spacers developed fully acceptable technique. Improvements made immediately following instruction were lost when patients were reevaluated months later. Few patients received spacers after they were recommended. Technique was markedly better with spacers. Most patients (76%) had initially proper technique with spacers, and most who had poor technique could learn and retain proper technique. CONCLUSIONS: Improper inhaler technique without spacers is very common among patients evaluated at home, and the majority of patients were unable to learn and retain proper technique. Most patients would benefit from using spacers with their inhalers. = 33 for first and second. = 26 for third. FRC = functional residual capacity. RV = residual volume. TLC = total lung capacity.¿., Fig. 3¿/PICK;0404f3;;;page;;;;yes;1¿ ¿/GRAPH;rk1000404003;comptd;;center;stack¿ ¿/CAPT;;;center;stack;2112n¿

Adult↗