Biomedical subjects

D H Johnson

Publications and source records attributed to D H Johnson.

At least 19 recordsLinked to original sources

PubMed2006

Impact of hemoglobin levels on outcomes of adjuvant chemotherapy in resected non-small cell lung cancer: the JBR.10 trial experience.

BACKGROUND: Cisplatin-induced anemia may correlate with adverse events, poor quality of life (QoL), decreased adjuvant chemotherapy (ACT) dose intensity, shorter relapse-free survival (RFS) or overall survival (OS). METHODS: The JBR.10 trial demonstrated significantly longer survival with adjuvant cisplatin and vinorelbine (n=242) compared to observation (n=240) in patients with resected NSCLC [Winton T, Livingston R, Johnson D, Rigas J, Johnston M, Butts C, et al. Vinorelbine plus cisplatin vs. observation in resected non-small-cell lung cancer. N Engl J Med 2005;352(25):2640-2]. This exploratory analysis evaluates the predictive value of baseline (in all patients) and during-treatment (in ACT arm only) hemoglobin (Hb) levels on OS and RFS when adjusted for prognostic factors. Baseline (in all patients) and during treatment (in ACT arm only) Hb levels were also correlated with adverse events, QoL, morbidity and ACT dose intensity. RESULTS: Baseline Hb did not predict RFS or OS. However, there was a trend to shorter OS (p=0.1) when baseline Hb was <120g/L. Lower baseline Hb predicted increased hospitalization (p=0.04) and worse QoL (SOB item, p=0.03) but had no impact on adverse events or dose intensity. There was a trend to longer RFS (p=0.08) in patients with lower nadir during-treatment Hb and to longer OS (p=0.06) and RFS (p=0.08) in patients with maximum during-treatment Hb drop >30% that was not maintained when ACT dose intensity was included in the model. Maximum during-treatment Hb drop >30% correlated with increased lethargy (p=0.003) and worse QoL (fatigue item, p=0.07). CONCLUSIONS: Lower baseline and during-treatment Hb levels seem associated with poorer QoL, fatigue and increased hospitalization. There is a trend for shorter OS in patients with lower baseline Hb levels.

Anemia↗

PubMed2004

Docetaxel combined with trastuzumab is an active regimen in HER-2 3+ overexpressing and fluorescent in situ hybridization-positive metastatic breast cancer: a multi-institutional phase II trial.

PURPOSE: To determine the efficacy and safety of weekly docetaxel and trastuzumab as first- or second-line therapy in women with HER-2-overexpressing metastatic breast cancer and to correlate the efficacy of trastuzumab with HER-2 status as determined by immunohistochemistry assay and fluorescent in situ hybridization (FISH). PATIENTS AND METHODS: Twenty-six women with HER-2-positive (HercepTest [Dako Corp, Carpenteria, CA]2 to 3+) metastatic breast cancer were enrolled onto this study of trastuzumab (4 mg/kg load; 2 mg/kg/wk administered intravenously) and docetaxel (35 mg/m2/wk for 6 weeks). RESULTS: Using an intent-to-treat analysis, the overall response rate was 50% (13 of 26 patients). Eight patients (31%) had a period of stable disease posttherapy. Among HER-2 3+ patients, the overall response rate was 63% (12 of 19 patients) compared with a 14% response rate (one of seven patients) for HER-2 2+ patients (P=.07). Patients with FISH-positive tumors experienced an overall response rate of 64%. Median time to progression was 12.4 months for the entire cohort (HER-2 3+ tumors, 12.3 months; HER-2 2+ lesions, 9.5 months) and median survival was 22.1 months. All HER-2 3+ patients were FISH-positive; the only HER-2 2+ patient responding to treatment was also FISH-positive. Grade 4 toxicities occurred in four patients; most toxicities were mild. CONCLUSION: Trastuzumab plus docetaxel is an active and well-tolerated regimen in women with HER-2 3+ overexpressing or FISH-positive metastatic breast cancer.

Adult↗

PubMed2004

Phase II study of the farnesyl transferase inhibitor R115777 in patients with sensitive relapse small-cell lung cancer.

BACKGROUND: R115777 (tipifarnib, Zarnestra) is a farnesyl transferase inhibitor that blocks the farnesylation of proteins involved in signal transduction pathways critical for cell proliferation and survival. This multicenter phase II study was conducted to determine the efficacy, tolerability and pharmacokinetics of R115777 in patients with relapsed small-cell lung cancer (SCLC). PATIENTS AND METHODS: Patients who had a partial or complete response to their initial chemotherapy regimen, followed by at least 3 months off treatment before relapse (sensitive relapse) were eligible. R115777 was administered in 3-week cycles at a dose of 400 mg orally twice daily for 14 consecutive days followed by 7 days off treatment. RESULTS: Twenty-two patients were enrolled. The median progression-free survival was 1.4 months and median overall survival was 6.8 months. Non-hematological toxicities were predominantly grade 1-2 and included nausea (64%) and fatigue (60%). Grade 3-4 granulocytopenia and thrombocytopenia occurred in 27% and 23% of patients, respectively. Febrile neutropenia was not observed. Pharmacokinetic studies demonstrated peak plasma concentrations of R115777 2.6-4.5 h after oral dosing and no significant drug accumulation. The trial was terminated because no objective responses were observed in 20 patients evaluable for response. CONCLUSIONS: R115777 showed no significant antitumor activity as a single agent in sensitive-relapse SCLC.

Adult↗

PubMed2003

Variation in management of community-acquired pneumonia requiring admission to Alberta, Canada hospitals.

Previous studies have shown small area variation in the rate of admission to hospital for patients with community-acquired pneumonia. We determined the rates of admission and length of stay for patients with community-acquired pneumonia in Alberta and the factors influencing admission rates and length of stay. Using hospital abstracts, hospital admissions for community-acquired pneumonia from 1 April 1994 to 31 March 1999 were compared. We classified Alberta hospitals according to geographical regions, by the number of beds, and by number of community-acquired pneumonia cases. There were 12,000 annual hospital discharges for community-acquired pneumonia costing over $40 million per year. The overall in-hospital mortality rate was 12% and the 1 year mortality rate was 26%. Compared with rural hospitals, regional and metropolitan hospitals admitted patients with greater severity of illness as demonstrated by greater in-hospital mortality, cost per case and comorbidity. Age-sex adjusted hospital discharge rates were significantly below the provincial average in both urban regions. Hospital discharge rates for residents in all rural regions and 4 of 5 regions with a regional hospital were significantly higher than the provincial average. After adjusting for comorbidity, the relative risk for a longer length of stay was 22% greater in regional hospitals and about 30% greater in urban hospitals compared to rural hospitals. Seasonal variation in the admission rate was evident, with higher rates in the winter of each year. We conclude that rural hospitals would be likely to benefit from a protocol to help with the admission decision and urban hospitals from a programme to reduce length of stay.

Adolescent↗

PubMed2003

Mortality during hospitalisation for pneumonia in Alberta, Canada, is associated with physician volume.

The association of mortality with patient factors (severity of illness, comorbidity), physician factors (specialty training, prehospitalisation visit, in-hospital consultation, volume of patients seen per physician) and healthcare organisation factors (patient-travel distances, regional beds per capita, admitting hospital-bed occupancy, admitting hospital-bed turnover, hospital location, volume of pneumonia cases per hospital) after hospital admission with community-acquired pneumonia was investigated using administrative data from Alberta, Canada from April 1, 1994-March 31, 1999. During the 5-yr study period there were 43,642 pneumonia hospitalisations, with an 11% in-hospital and 26% 1-yr mortality. Patient severity of illness and comorbidity were the strongest predictors of increased mortality. Physicians with the highest in-hospital pneumonia patient volume (>27 patients x yr(-1)) cared for patients with greater severity/comorbidity, but with decreased odds of in-hospital mortality, compared with the lowest volume physicians (less than seven patients per year). The effects of internal medicine specialist or subspecialist care were mixed, with a reduction in deaths for the first 72 h and an increase in in-hospital deaths. Prehospitalisation visit by a physician was associated with decreased mortality. Healthcare organisation factors were the least strong predictor of mortality, demonstrating an effect only for 1-yr mortality in those discharged alive from hospital. Admissions to larger volume or metropolitan hospitals were associated with a decrease in mortality. Severity of illness and comorbidity had the strongest association with mortality. The first association of high-volume physician and pre-hospital care with decreased in-hospital mortality for community-acquired pneumonia is reported.

Adolescent↗

PubMed2003

[Physiology of aqueous humor outflow resistance: its relation to giant vacuoles].

About 2% of the French population over the age of 40 suffers from open angle glaucoma, a disorder for which ocular hypertension is the main risk factor. Improving our understanding of primary open-angle glaucoma physiopathology has been an area of intense research for nearly a century. The main aqueous outflow system in the human eye includes the trabecular meshwork, Schlemm's canal, aqueous veins, and the episcleral veins. Schlemm's canal is bordered by endothelium cells, many of which contain giant vacuoles, structures that are sensitive to intraocular pressure and that therefore can act as markers of active outflow. Giant vacuoles are most often found near collector channels in normal eyes, probably in areas of low downstream pressure. In the glaucoma eye, determining where giant vacuoles form could help localize the site of pathological outflow resistance.

Aqueous Humor↗

PubMed2002

The influence of gender on survival and tumor recurrence following adjuvant therapy of completely resected stages II and IIIa non-small cell lung cancer.

This study evaluates the influence of gender on survival and tumor recurrence following adjuvant therapy of completely resected stages II and IIIa non-small cell lung cancer (NSCLC). The Eastern Cooperative Oncology Group conducted a randomized prospective trial of adjuvant therapy in patients with completely resected stages II and IIIa NSCLC. A laboratory correlative study assessed the prevalence and prognostic significance of p53 and K-ras mutations. Patients were randomized to receive either radiotherapy (RT) alone or four cycles of cisplatin and VP-16 administered concurrently with radiotherapy (CRT). Median survival was 35 months for the 285 men and 41 months for the 203 women enrolled in the study (P = 0.12). The relative risk (RR) of death for men vs women was 1.19 (95% confidence interval [CI], 0.95-1.49). Median survival of the 147 men and 95 women randomized to the RT arm was 39 months each (P = 0.35). Median survival of the 138 men and 108 women randomized to the CRT arm was 30 and 42 months, respectively (P = 0.18). Disease recurrence patterns were similar between the genders. Univariate and multivariate analyses demonstrated improved survival for women with tumors of non-squamous histology (P < 0.01). The distribution of p53 and K-ras mutations was similar between the genders and had no influence on survival. Gender does not influence survival following adjuvant RT or CRT administered to patients with completely resected stages II and IIIa NSCLC. However, women with non-squamous histology have increased survival when compared to men.

Adult↗

PubMed2001

Genetic modification of human trabecular meshwork with lentiviral vectors.

Glaucoma, a group of optic neuropathies, is the leading cause of irreversible blindness. Neuronal apoptosis in glaucoma is primarily associated with high intraocular pressure caused by chronically impaired outflow of aqueous humor through the trabecular meshwork, a reticulum of mitotically inactive endothelial-like cells located in the angle of the anterior chamber. Anatomic, genetic, and expression profiling data suggest the possibility of using gene transfer to treat glaucomatous intraocular pressure dysregulation, but this approach will require stable genetic modification of the differentiated aqueous outflow tract. We injected transducing unit-normalized preparations of either of two lentiviral vectors or an oncoretroviral vector as a single bolus into the aqueous circulation of cultured human donor eyes, under perfusion conditions that mimicked natural anterior chamber flow and maintained viability ex vivo. Reporter gene expression was assessed in trabecular meshwork from 3 to 16 days after infusion of 1.0 x 10(8) transducing units of each vector. The oncoretroviral vector failed to transduce the trabecular meshwork. In contrast, feline immunodeficiency virus and human immunodeficiency virus vectors produced efficient, localized transduction of the trabecular meshwork in situ. The results demonstrate that lentiviral vectors permit efficient genetic modification of the human trabecular meshwork when delivered via the afferent aqueous circulation, a clinically accessible route. In addition, controlled comparisons in this study establish that feline and human immunodeficiency virus vectors are equivalently efficacious in delivering genes to this terminally differentiated human tissue.

Aged↗

PubMed2001

Outcome of patients with a performance status of 2 in Eastern Cooperative Oncology Group Study E1594: a Phase II trial in patients with metastatic nonsmall cell lung carcinoma .

BACKGROUND: Eastern Cooperative Oncology Group (ECOG) Study E1594 compared paclitaxel and cisplatin with three newer chemotherapy doublets in the treatment of patients with advanced nonsmall cell lung carcinoma (NSCLC). The accrual of patients with an ECOG performance status (PS) of 2 was discontinued due to a perceived rate of unacceptable toxicity. METHODS: Patients were stratified by PS and randomized to one of the following treatments: 1) paclitaxel (135 mg/m2) over 24 hours with cisplatin (75 mg/m2) on a 21-day cycle; 2) cisplatin (100 mg/m2) with gemcitabine (1 g/m2) on Days 1, 8, and 15 on a 28-day cycle; 3) cisplatin (75 mg/m2) with docetaxel (75 mg/m2) on a 21-day cycle; and 4) paclitaxel (225 mg/m2) over 3 hours with carboplatin (area under the curve, 6). All tests of statistical significance were two-sided. RESULTS: Sixty-eight patients with an ECOG PS of 2 were enrolled, and 64 patients were evaluable for toxicity and response. Fifty-six percent of 64 evaluable patients were male, and 81% had Stage IV disease. Grade 3-4 hematologic toxicities occurred in > 50% of the patients in each treatment group. Nonhematologic Grade 3-4 toxicities occurred significantly less often in the paclitaxel and carboplatin arm (P = 0.0032). The overall rate of toxicity did not differ significantly from the rate of toxicity in the PS-0 or PS-1 cohorts. There were 5 deaths (7.35%) among 68 patients with a PS of 2 during therapy; however, only 2 of those deaths were attributed to therapy. The overall response rate for the 64 evaluable patients was 14%. The overall median survival of all 68 patients with a PS of 2, as determined by an intent-to-treat analysis, was 4.1 months. CONCLUSIONS: Patients with advanced NSCLC and a PS of 2 experienced a large number of adverse reactions and overall poor survival. A comparison with patients with a PS of 0-1 suggests that these events and the shorter survival were related to disease process rather than treatment. Alternative strategies need to be explored with therapy specifically tailored for this group of patients.

Aged↗

PubMed2001

Combined etoposide, ifosfamide, and cisplatin in the treatment of patients with advanced thymoma and thymic carcinoma: an intergroup trial.

BACKGROUND: Patients with thymic tumors (thymoma and thymic carcinoma) are known to respond to a variety of chemotherapeutic agents, including single-agent ifosfamide and cisplatin with etoposide. The purpose of this trial was to evaluate the response rate, progression free survival, overall survival, and toxicity of combined etoposide, ifosfamide, and cisplatin (VIP) in patients with advanced thymoma and thymic carcinoma. METHODS: From July 1995 through February 1997, 34 patients with advanced thymoma or thymic carcinoma were entered on trial to receive etoposide (75 mg/m2 on Days 1-4) ifosfamide (1.2 g/m2 on Days 1-4), and cisplatin (20 mg/m2 on Days 1-4). Cycles were repeated every 3 weeks for four total cycles. RESULTS: Among 28 evaluable patients (pathology review excluded 6 patients), there were no complete responses and 9 partial responses (complete and partial responses combined, 32%; 95% confidence interval, 16-52%). The median follow-up was 43 months (range, 12.8-52.3 months), the median duration of response was 11.9 months (range, < 1-26 months), and the median overall survival was 31.6 months. Based on Kaplan-Meier estimates, the 1-year and 2-year survival rates were 89% and 70%, respectively. The toxicity was predominantly myelosuppression. CONCLUSIONS: The VIP regimen has moderate activity in patients with advanced thymic malignancies. However, with limited follow-up, the results of this trial appear to be inferior to other chemotherapy regimens reported in large Phase II trials performed in patients with this disease.

Adult↗

PubMed2001

Topotecan versus observation after cisplatin plus etoposide in extensive-stage small-cell lung cancer: E7593--a phase III trial of the Eastern Cooperative Oncology Group.

PURPOSE: To determine the efficacy of topotecan in combination with standard chemotherapy in previously untreated patients with extensive-stage small-cell lung cancer (SCLC), the Eastern Cooperative Oncology Group (ECOG) conducted a phase III trial. PATIENTS AND METHODS: Eligible patients had measurable or assessable disease and an ECOG performance status of 0 to 2; stable brain metastases were allowed. All patients received four cycles of cisplatin and etoposide every 3 weeks (step 1; PE). Patients with stable or responding disease were then randomized to observation or four cycles of topotecan (1.5 mg/m(2)/d for 5 days, every 3 weeks; step 2). A total of 402 eligible patients were registered to step 1, and 223 eligible patients were registered to step 2 (observation, n = 111; topotecan, n = 112). RESULTS: Complete and partial response rates to induction PE were 3% and 32%, respectively. A 7% response rate was observed with topotecan (complete response, 2%; partial response, 5%). The median survival time for all 402 eligible patients was 9.6 months. Progression-free survival (PFS) from date of randomization on step 2 was significantly better with topotecan compared with observation (3.6 months v 2.3 months; P <.001). However, overall survival from date of randomization on step 2 was not significantly different between the observation and topotecan arms (8.9 months v 9.3 months; P =.43). Grade 4 neutropenia and thrombocytopenia occurred in 50% and 3%, respectively, of PE patients in step 1 and 60% and 13% of topotecan patients in step 2. Grade 4/5 infection was observed in 4.6% of PE patients and 1.8% of topotecan patients. Grade 3/4 anemia developed in 22% of patients who received topotecan. No difference in quality of life between topotecan and observation was observed at any assessment time or for any of the subscale scores. CONCLUSION: Four cycles of PE induction therapy followed by four cycles of topotecan improved PFS but failed to improve overall survival or quality of life in extensive-stage SCLC. Four cycles of standard PE remains an appropriate first-line treatment for extensive-stage SCLC patients with good performance status.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2001

Twenty-two years of phase III trials for patients with advanced non-small-cell lung cancer: sobering results.

PURPOSE: To determine the changes in clinical trials and outcomes of patients with advanced-stage non-small-cell lung cancer (NSCLC) treated on phase III randomized trials initiated in North America from 1973 to 1994. PATIENTS AND METHODS: Phase III trials for patients with advanced-stage NSCLC were identified through a search of the National Cancer Institute's Cancer Therapy Evaluation Program database from 1973 to 1994, contact with Cooperative Groups, and by literature search of MEDLINE. Patients with advanced NSCLC treated during a similar time interval were also examined in the SEER database. Trends were tested in the number of trials, in the number and sex of patients entered on the trials, and in survival over time. RESULTS: Thirty-three phase III trials were initiated between 1973 and 1994. Twenty-four trials (73%) were initiated within the first half of this period (1973 to 1983) and accounted for 5,359 (64%) of the 8,434 eligible patients. The median number of patients treated per arm of the trials rose from 77 (1973 to 1983) to 121 (1984 to 1994) (P <.001). Five trials (15%) showed a statistically significant difference in survival between treatment arms, with a median prolongation of the median survival of 2 months (range, 0.7 to 2.7 months). CONCLUSION: Analysis of past trials in North America shows that the prolongation in median survival between two arms of a randomized study was rarely in excess of 2 months. Techniques for improved use of patient resources and appropriate trial design for phase III randomized therapeutic trials with patients with advanced NSCLC need to be developed.

Adult↗

PubMed2001

A randomized Phase II trial in patients with carcinoma of an unknown primary site.

BACKGROUND: Current therapy for patients with carcinoma of an unknown primary site (CUP) is inadequate. To develop less toxic and more effective therapies for patients with CUP, a multicenter, randomized, Phase II study was conducted. Patients with CUP received either carboplatin and etoposide (CE) or a combination of paclitaxel, 5-fluorouracil, and leucovorin (TFL). METHODS: Patients randomized to Arm A received paclitaxel, 175 mg/m(2), intravenously over 3 hours on Day 1 followed by leucovorin, 300 mg, over 30-60 minutes and 5-fluorouracil, 350 mg/m(2), both intravenously on Days 1-3. Patients randomized to Arm B received etoposide, 100 mg/m(2), intravenously on Days 1-3 and carboplatin at an area under the curve of 6 on Day 1 only. The cycles in both treatment arms were repeated every 28 days. Patients were followed for tumor response, survival, and toxicity. RESULTS: Thirty-four patients were enrolled, 32 of whom were evaluable for response. An identical overall response rate of 19% (95% confidence interval, 4-45%) was noted in each treatment arm. The median survival for the entire study population was 194 days. The median survivals observed in Arm A and Arm B were 251 days and 194 days, respectively (P = 0.91 [difference not significant]). Hematologic toxicity on Arm B was considerable with 29% of the patients developing neutropenia and fever. Toxicity on Arm A was modest. CONCLUSIONS: In this randomized Phase II trial, CE and TFL appeared to have modest activity in CUP patients, with response rates similar to those reported with previously described chemotherapy regimens. Toxicity with CE was more severe than expected, although TFL was found to be well tolerated.

Adult↗

PubMed2001

Lack of prognostic significance of p53 and K-ras mutations in primary resected non-small-cell lung cancer on E4592: a Laboratory Ancillary Study on an Eastern Cooperative Oncology Group Prospective Randomized Trial of Postoperative Adjuvant Therapy.

PURPOSE: To determine the prognostic and predictive significance of p53 and K-ras mutations in patients with completely resected non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Patients were randomized preoperatively to receive adjuvant postoperative radiotherapy (Arm A) or radiotherapy plus concurrent chemotherapy (Arm B). p53 protein expression was studied by immunohistochemistry (IHC) and p53 mutations in exons 5 to 8 were evaluated by single-strand conformational analysis. K-ras mutations in codons 12, 13, and 61 were determined using engineered restriction fragment length polymorphisms. RESULTS: Four hundred eighty-eight patients were entered onto E3590; 197 tumors were assessable for analysis. Neither presence nor absence of p53 mutations, p53 protein expression, or K-ras mutations correlated with survival or progression-free survival. There was a trend toward improved survival for patients with wildtype K-ras (median, 42 months) compared with survival of patients with mutant K-ras who were randomized to chemotherapy plus radiotherapy (median, 25 months; P = .09). Multivariate analysis revealed only age and tumor stage to be significant prognostic factors, although there was a trend bordering on statistical significance for K-ras (P = .066). Analysis of survival difference by p53 by single-stranded conformational polymorphism and IHC, interaction of p53 and K-ras, interaction of p53 and treatment arm, nodal station, extent of surgery, weight loss, and histology did not reach statistical significance. CONCLUSION: p53 mutations and protein overexpression are not significant prognostic or predictive factors in resected stage II or IIIA NSCLC. K-ras mutations may be a weak prognostic marker. p53 or K-ras should not be routinely used in the clinical management of these patients.

Carcinoma, Non-Small-Cell Lung↗

PubMed2001

Beta-adrenergic blocker therapy and the trabecular meshwork.

PURPOSE: To determine whether beta-adrenergic blocker (beta-blocker) therapy for glaucoma causes changes in the trabecular meshwork due to underperfusion. METHODS: Thirty-five eyes from 19 donors with primary open-angle glaucoma (POAG) were divided into three groups: eyes receiving beta-blocker therapy along with standard medications, eyes receiving standard medications but no beta-blockers, and eyes with elevated intraocular pressure but receiving no therapy. Transmission electron microscopy was used to assess the extracellular material of the cribriform region, the structure of the trabecular lamellae, and pigmentation of the trabecular cells. Six eyes from four normal donors were used as controls. RESULTS: No specific changes in the trabecular meshwork were found in eyes receiving beta-blocker therapy. The amount and composition of the extracellular matrix of the cribriform region and the morphology of the lamellae were similar among the three groups of eyes with POAG. Pigmentation of trabecular cells appeared to be a marker for aqueous flow, as significantly more cells contained pigment in regions of the meshwork with thin or normal lamellae than in regions with thickened and fused lamellae. These regions were variable around the circumference of the eye, and were similar between eyes with and without beta-Blocker therapy. CONCLUSION: beta-Blocker therapy could not be proven to cause underperfusion changes in the trabecular meshwork or other discernible effects. Preferential pathways for aqueous flow probably exist within regions of the trabecular meshwork, as evidenced by lamellar appearance and pigmentation of the adjacent trabecular cells.

Acetazolamide↗

PubMed2001

The long-term outcome of glaucoma filtration surgery.

PURPOSE: To determine the long-term outcome of glaucoma filtration surgery in preserving vision. Visual loss from progressive glaucomatous damage and from complications of surgery, both short and long term, were included. METHODS: A retrospective, community-based, longitudinal study of residents of Olmsted County, Minnesota, who were newly diagnosed with open-angle glaucoma between 1965 and 1980 and underwent filtration surgery in these or subsequent years through 1998. Intraocular pressure (IOP), visual acuity, visual fields, and progression to legal blindness were monitored. Kaplan-Meier analysis was used to determine the cumulative probabilities of changes in these parameters. RESULTS: 73 eyes of 49 patients underwent conventional filtration surgery. Analysis of the first eye having surgery revealed a mean preoperative IOP of 27.6 +/- 8.5 mm dropping to 16.7 +/- 5.6 mm at year one, and remaining in this range throughout follow-up (14.7 +/- 3.0 mm at 10 years; with or without use of medications). The probability of progression to blindness was 46% at 10 years after surgery, as calculated by Kaplan-Meier analysis. Eyes going blind had a postoperative IOP equal to or lower than those not becoming blind (14.0 +/- 4.4 vs. 15.4 +/- 3.0 at postoperative year 10). Eyes going blind had more advanced field loss at the time of surgery, with scotomas above and below the horizontal axis, than eyes not going blind, which had scotomas in only one hemifield. Three patients developed late bleb leaks; two patients developed endophthalmitis. The probability of undergoing cataract surgery was 37% by 10 years postoperatively, which did not differ significantly from the cohort of patients not undergoing surgery at a comparable time point. CONCLUSIONS: Filtration surgery was associated with a 54% probability of preservation of vision from progression to legal blindness at 10 years after surgery. Patients becoming blind had more advanced field loss at the time of surgery; IOP was similar between those going blind and those retaining vision.

Aged↗

PubMed2001

Estimated incidence of open-angle glaucoma in Olmsted County, Minnesota.

PURPOSE: To determine the incidence rates of open-angle glaucoma (OAG) in Olmsted County, MINNESOTA: DESIGN: Retrospective population-based estimate of incidence. PARTICIPANTS: From the medical histories of 60,666 residents of Olmsted County, Minnesota, who had ocular diagnoses during the study period, 114 subjects with newly diagnosed OAG were identified. METHODS: The database of the Rochester Epidemiology Project was used to identify all Olmsted County residents with a coded diagnosis of OAG, glaucoma suspect, or ocular hypertension during the period 1965 to 1980. Subjects newly diagnosed with and treated for OAG who also had documented clinical evidence of elevated intraocular pressure, optic nerve damage, and/or visual field loss consistent with glaucoma were included as incident cases. Population data for Olmsted County were drawn from United States Census data. Crude incidence data were adjusted to the age and gender distribution of the 1990 United States white population. MAIN OUTCOME MEASURES: Estimated incidence rates of OAG. RESULTS: The overall age- and gender-adjusted annual incidence rate of OAG in a predominantly Caucasian population is conservatively estimated to be 14.5 per 100,000 population. The rates increased with age from 1.6 in the fourth decade of life to 94.3 in the eighth decade. There was no significant difference in incidence by gender. The average annual rate of OAG in the last 2 years of the study was 27.7 compared with 12.3 before 1979. This difference is suggestive of the effect of the introduction of a new medical therapy (timolol) for OAG during the last 2 years. CONCLUSIONS: The incidence rates of OAG increase markedly with advancing age, and screening efforts should be targeted at both men and women in the older age groups. The advent of new diagnostic and therapeutic modalities can have an effect on incidence rates.

Adolescent↗

PubMed2001

Phase I trial of outpatient weekly docetaxel, carboplatin and concurrent thoracic radiation therapy for stage III unresectable non-small-cell lung cancer: a Vanderbilt cancer center affiliate network (VCCAN) trial.

PURPOSE: Docetaxel, an active agent for non-small cell lung cancer (NSCLC), has demonstrated activity as a radiosensitizer in numerous pre-clinical studies. We conducted a phase I trial to determine the maximum-tolerated dose (MTD) and dose-limiting toxicities (DLT) of weekly Docetaxel, Carboplatin with concurrent thoracic radiation therapy (TRT) in patients with unresectable stage III NSCLC. PATIENTS AND METHODS: In this phase I clinical trial, Docetaxel was administered weekly as a 1-h intravenous infusion for 6 weeks with a starting dose of 20 mg/m(2). Docetaxel doses were escalated by 10 mg/m(2) increments in successive cohorts of three patients. DLT was defined as grade >or=3 nonhematologic and hematologic toxicity according to RTOG toxicity criteria. Once the DLT of Docetaxel alone was reached, weekly Carboplatin (AUC 2) was added at a DLT-2 dose of Docetaxel (two dose levels below that of dose limiting toxicity). Docetaxel doses were again escalated at 10 mg/m(2) increments in successive cohorts of three new patients to define further DLT and MTD of Docetaxel/Carboplatin with TRT. TRT was administered to the primary tumor and regional lymph nodes (40 Gy) followed by a boost to the tumor (20 Gy). RESULTS: Fifteen patients were entered onto this study with Docetaxel alone through three dose escalations (from 20 to 40 mg/m(2) weekly). The DLT of weekly Docetaxel/TRT was esophagitis and the MTD was 30 mg/m(2) per week for 6 weeks. Nine more patients were added with the Docetaxel/Carboplatin/TRT regimen. The DLT of weekly Docetaxel/Carboplatin with TRT was esophagitis and the MTD of Docetaxel was 20 mg/m(2) per week with weekly Carboplatin (AUC 2). There were 2 complete responses and 13 partial responses in 25 evaluable patients (RR 60%). CONCLUSIONS: This combination regimen has activity with manageable toxicity in patients with stage III NSCLC. A phase II study is planned to define activity.

Aged↗