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D H Johnson

Publications and source records attributed to D H Johnson.

At least 91 records · Page 5Linked to original sources
PubMed1998

Comparison of protein mixtures in aqueous humor by membrane preconcentration - capillary electrophoresis - mass spectrometry.

The significance of proteomic research is coupled with the recent exponential growth of these investigations. Currently, the most popular techniques used for these studies include the coupling of 1- and 2-dimensional electrophoresis with mass spectrometric analysis of the extracted and digested proteins. However, detection limits of gel staining methods have led to a search for complimentary techniques that afford the detection of lower concentrations of biologically relevant proteins. In the present studies, we have evaluated the applicability of on-line capillary electrophoresis - mass spectrometry (CE-MS) for this application. Specifically, we used membrane preconcentration-CE-MS (mPC-CE-MS) to analyze 13 samples of human aqueous humor (AH) from patients with various ocular pathologies (cataract, cataract plus glaucoma, and cataract plus pseudoexfoliation syndrome). This approach enabled rapid analysis of a relatively large volume (1 microL of each specimen, and a protein map for each was created. Measured average molecular weights (Mr) were used to tentatively identify proteins after search of the SWISS-PROT database using TagIdent from ExPaSy. Among those proteins tentatively identified are beta-2 microglobulin (Mr 11731.2), apolipoprotein A1 (Mr 28078.6) and serum albumin (Mr 66400). Proteins with Mr of 4349 (unidentified), 11731.2 (beta-2 microglobulin), 13400-14100 (immunoglobulin fragments), 28078.2 (apolipoprotein A1) and approximately 68000 (serum albumin) were observed in the majority of specimens. Generally no significant differences were noted in the protein composition of aqueous humor samples from different pathologies. However, the absence of an Mr 13345 protein and its oxidized form (Mr 13361) in samples from patients with pseudoexfoliation syndrome was noted. Occasionally the alpha-and beta-chains of hemoglobin, a contaminant in aqueous humor introduced during sampling, were also detected. We conclude from these studies that mPC-CE-MS is an attractive complimentary technique for proteome research, as this approach enables direct mapping and characterization of low concentrations of proteins that are present in complex physiologically derived fluids.

Apolipoprotein A-I↗
PubMed1998

The probability of blindness from open-angle glaucoma.

OBJECTIVE: This study aimed to determine the probability of a patient developing legal blindness in either one or both eyes from newly diagnosed and treated open-angle glaucoma (OAG) after starting medical or surgical therapy or both. DESIGN: The study design was a retrospective, community-based descriptive study. PARTICIPANTS: Two hundred ninety-five residents of Olmsted County, Minnesota, newly diagnosed with, and treated for, OAG between 1965 and 1980 with a mean follow-up of 15 years (standard deviation +/- 8 years) participated. INTERVENTION: Kaplan-Meier cumulative probability of blindness was estimated for patients treated and followed for OAG. MAIN OUTCOME MEASURES: Legal blindness, defined as a corrected visual acuity of 20/200 or worse, and/or visual field constricted to 20 degrees or less in its widest diameter with the Goldmann 1114e test object or its equivalent on automated perimetry, secondary to glaucomatous loss, was measured. RESULTS: At 20-years' follow-up, the Kaplan-Meier cumulative probability of glaucoma-related blindness in at least one eye was estimated to be 27% (95% confidence interval, 20%-33%), and for both eyes, it was estimated to be 9% (95% confidence interval, 5%-14%). At the time of diagnosis, 15 patients were blind in at least 1 eye from OAG. CONCLUSION: A retrospective study of a white population determined that the risk of blindness from newly diagnosed and treated OAG may be considerable.

Aged↗
PubMed1998

Single-neuron modeling of LSO unit responses.

We investigated, using a computational model, the biophysical correlates of measured discharge patterns of lateral superior olive (LSO) neuron responses to monaural and binaural stimuli. The model's geometry was based on morphological data, and static electric properties of the model agree with available intracellular responses to hyperpolarizing current pulses. Inhibitory synapses were located on the soma and excitatory ones on the dendrites, which were modeled as passive cables. The active properties of the model were adjusted to agree with statistical measures derived from extracellular recordings. Calcium-dependent potassium channels supplemented the usual Hodgkin-Huxley characterization for the soma to produce observed serial interspike interval dependence characteristics. Intracellular calcium concentration is controlled by voltage- and calcium-dependent potassium channels and by calcium diffusion and homeostatic mechanisms. By adjusting the density of the calcium-dependent potassium channels, we could span the observed range of transient response patterns found in different LSO neurons. Inputs from the two ears were modeled as Poisson processes to describe the responses to tone-burst stimuli. Transient and sustained responses to monaural and binaural tone-burst stimuli over a wide range of stimulus conditions could be well described by varying only the model's inputs. As found in recordings, model responses having similar discharge rates but different binaural stimulus combinations exhibited differences in interval statistics.

Acoustic Stimulation↗
PubMed1998

Pharmacokinetics of an intravenous-oral versus intravenous-mesna regimen in lung cancer patients receiving ifosfamide.

PURPOSE: To compare the pharmacokinetics of the approved I.V. (intravenous) mesna regimen and an investigational I.V.-oral regimen that could be used in outpatients who receive ifosfamide. PATIENTS AND METHODS: The I.V. regimen consisted of three I.V. mesna doses given at 0, 4, and 8 hours after ifosfamide administration. The investigational regimen included an I.V. mesna dose given concurrently with ifosfamide, followed 2 and 8 hours later by oral administration of mesna tablets. I.V. and oral mesna doses equaled 20% and 40%, respectively, of the ifosfamide dose. The study subjects were 12 lung cancer patients who received ifosfamide 1.2 g/m2 daily for 5 days. The patients were randomized to receive either the I.V.-oral or I.V. mesna regimen on day 1, followed by crossover to the other regimen on days 2 through 5 of ifosfamide treatment. The urinary profiles of mesna and dimesna excretion were determined on days 1, 2, and 5; pharmacokinetic parameters for blood samples were determined only on day 5. RESULTS: During the first 12 hours after ifosfamide administration, the amount of mesna excreted and the profile of urinary mesna excretion was similar for both regimens; however, the I.V.-oral regimen showed less fluctuation in the excretion rate and higher trough values. During hours 12 to 24, about eightfold more mesna was excreted by patients given the I.V.-oral than the I.V. regimen. CONCLUSION: These pharmacokinetic data show that the I.V.-oral regimen should be at least as uroprotective as the I.V. mesna regimen. Patients may also benefit from the I.V.-oral regimen because of the higher trough values during hours 0 through 12 and the sustained urinary mesna excretion during hours 12 through 24.

Administration, Oral↗
PubMed1998

Gene therapy for breast and ovarian cancer with BRCA1.

As an initial step toward gene therapy for ovarian cancer, we conducted a Phase 1 trial to assess the pharmacokinetics and toxicity of intraperitoneal BRCA1sv retroviral vector therapy. Gene transfer and expression were documented by PCR, southern blot, RT-PCR and nuclease protection assays. Pharmacokinetics were assessed by PCR and southern blots detecting vector DNA, and toxicity was evaluated by clinical exam and fluid analysis. Three of twelve patients developed an acute sterile peritonitis which spontaneously resolved within 48 hours. Plasma and peritoneal antibodies to the retroviral envelope protein were detected only in patients treated with the highest dose levels but not in others, despite repeat dosing for an interval of up to four months. Eight patients showed stable disease for 4 to 16 weeks. Three patients showed tumor reduction with diminished miliary tumor implants at reoperation (two patients) and radiographic shrinkage of measurable disease (one patient). Ovarian cancer may provide an imporant model for retroviral gene therapy studies due to vector stability, minimal antibody response, and access to tumor by intraperitoneal therapy.

Journal Article↗
PubMed1998

Localization of the stress proteins alpha B-crystallin and trabecular meshwork inducible glucocorticoid response protein in normal and glaucomatous trabecular meshwork.

PURPOSE: To examine the differential staining of two potential stress-response markers, alpha B-crystallin and the trabecular meshwork inducible glucocorticoid response protein (TIGR), in meshwork from normal and glaucomatous human eyes. METHODS: Trabecular meshwork from 35 eyes from 23 donors with either primary open-angle glaucoma, pseudoexfoliative glaucoma, or low-tension glaucoma, and from age-matched normal eyes, was examined. Sagittal and tangential frozen sections were stained with polyclonal antibodies to alpha B-crystallin or TIGR and then by a fluorescent secondary antibody. RESULTS: In normal eyes, labeling for alpha B-crystallin occurred in the subendothelial region of Schlemm's canal and outer corneoscleral regions, whereas TIGR labeling was found in the inner uveal meshwork region and the anterior portion of the meshwork. In contrast, in many glaucomatous eyes, labeling for alpha B-crystallin and TIGR occurred in more regions of the meshwork and appeared more intense than in normal eyes, regardless of the type or clinical severity of glaucoma. CONCLUSIONS: The differences in localization of alpha B-crystallin and TIGR may relate to functional specialization within meshwork tissues. The increase in the staining for these proteins in glaucomatous eyes could involve environmental and genetic factors in the disease processes.

Aged↗
PubMed1998

Recent advances with chemotherapy for NSCLC: the ECOG experience. Eastern Cooperative Oncology Group.

Management of disseminated non-small-cell lung cancer has changed over the past 10 years. Newer agents, such as vinorelbine (Navelbine) and paclitaxel (Taxol), have been shown to modestly improve survival in patients with advanced disease when administered in conjunction with cisplatin (Platinol). Compared with older regimens consisting of cisplatin and a Vinca alkaloid or a podophyllotoxin, the newer regimens yield a 10- to 15-week improvement in median survival and an additional 10% to 15% in 1-year survival. Based on these results derived from randomized trials, it appears that metastatic non-small-cell lung cancer patients with good performance status should be treated with regimens containing either vinorelbine or paclitaxel in conjunction with cisplatin.

Antineoplastic Agents, Phytogenic↗
PubMed1998

Gene transfer to the human trabecular meshwork by anterior segment perfusion.

PURPOSE: To determine whether adenovirus vectors are capable of transferring a foreign active protein to the perfused anterior segment of the human eye. METHODS: Primary cultures from the human trabecular meshwork tissue were exposed to replication-deficient adenovirus Av1LacZ4 carrying the reporter beta-galactosidase gene driven by the Rous Sarcoma Virus promoter. Anterior segments of six pairs of human eyes from normal donors were placed in organ culture and were perfused with culture medium at 2.5 microl/min constant flow. After 24 hours, one eye was injected once with 8 X 10(8) plaque-forming units (20 microl) of the viral vector, while the paired eye was injected with vehicle. Forty-eight hours (four pairs) and 7 days (two pairs) after injection, tissues were fixed, were assayed histochemically for transferred enzyme activity, and were analyzed morphologically. RESULTS: In monolayers, gene transfer occurs very efficiently in all distinct types of human outflow pathway cells. All human anterior segments injected with the adenovirus vector showed active gene transfer in cells of the outflow pathway: trabecular, juxtacanalicular, and inner wall of Schlemm's canal. Expression of the reporter enzyme was still present at 7 days after treatment. No activity was observed in any of the paired, vehicle-injected controls. Cell morphology and tissue architecture appeared normal in treated and control tissues, although some trabecular cell loss was observed in the corneoscleral and uveal regions of the perfused treated eyes. CONCLUSIONS: Adenoviral vectors were able to transfer active foreign genes into perfused, intact human trabecular meshwork.

Adenoviridae↗
PubMed1997

Second primary cancers related to smoking and treatment of small-cell lung cancer. Lung Cancer Working Cadre.

BACKGROUND: An increased risk of second primary cancers has been reported in patients who survive small-cell carcinoma of the lung. The treatment's contribution to the development of second cancers is difficult to assess, in part because the number of long-term survivors seen at any one institution is small. We designed a multi-institution study to investigate the risk among survivors of developing second primary cancers other than small-cell lung carcinoma. METHODS: Demographic, smoking, and treatment information were obtained from the medical records of 611 patients who had been cancer free for more than 2 years after therapy for histologically proven small-cell lung cancer, and person-years of follow-up were cumulated. Population-based rates of cancer incidence and mortality were used to estimate the expected number of cancers or deaths. The actuarial risk of second cancers was estimated by the Kaplan-Meier method. RESULTS: Relative to the general population, the risk of all second cancers among these patients (mostly non-small-cell cancers of the lung) was increased 3.5-fold. Second lung cancer risk was increased 13-fold among those who received chest irradiation in comparison to a sevenfold increase among nonirradiated patients. It was higher in those who continued smoking, with evidence of an interaction between chest irradiation and continued smoking (relative risk = 21). Patients treated with various forms of combination chemotherapy had comparable increases in risk (9.4- to 13-fold, overall), except for a 19-fold risk increase among those treated with alkylating agents who continued smoking. IMPLICATIONS: Because of their substantially increased risk, survivors should stop smoking and may consider entering trials of secondary chemoprevention.

Actuarial Analysis↗
PubMed1997

Induction cisplatin/vinblastine and irradiation vs. irradiation in unresectable squamous cell lung cancer: failure patterns by cell type in RTOG 88-08/ECOG 4588. Radiation Therapy Oncology Group. Eastern Cooperative Oncology Group.

PURPOSE: To analyze disease failure patterns by pretreatment characteristics and treatment groups in a prospective randomized trial. METHODS AND MATERIALS: Patients with medically inoperable Stage II, unresectable IIIA and IIIB nonsmall cell lung cancer with KPS > or =70 and weight loss < or =5% were randomized to one of three treatment groups: standard radiation therapy with 60 Gy at 2.0 Gy per day (STD RT), induction chemotherapy with cisplatin 100 mg/m2 days 1 and 29 with vinblastine 5 mg/m2 weekly for 5 weeks followed by 60 Gy at 2.0 Gy per day (CT + RT), or hyperfractionated radiation therapy with 69.6 Gy at 1.2 Gy b.i.d. (HFX RT). Of 490 patients enrolled, 458 were evaluable. Minimum and median periods of observation for this analysis were 4 years and 6 years, respectively. RESULTS: Pretreatment characteristics were equally distributed. Toxicities were previously reported. Median survival rates were 11.4, 13.6, and 12.3 months for STD RT, CT + RT, and HFX RT, respectively (log rank p = 0.05, Wilcoxon p = 0.04). Survivals were 20, 31, and 24% at 2 years, and 4, 11, and 9% at 4 years in the STD RT, CT + RT, and HFX RT groups, respectively. There were no differences in local tumor control rates among the treatments. Patterns of first failure showed less distant metastasis (DM) (other than brain) for CT + RT compared to the RT alone arms (p = 0.04). Within squamous cell carcinoma (SCC), DM (other than brain) rates were 43%, 16%, and 38% in SCC for STD RT, CT + RT, and HFX RT, respectively (p = 0.0015). Patients with peripheral/chest wall lesions were significantly more likely to fail first in the thorax when treated on STD RT compared to CT + RT and HFX RT (p = 0.009). Survival rates were similar among the treatment arms for patients with squamous cell carcinoma. Among patients with nonsquamous cell carcinoma, failure patterns did not differ by treatment group, but survival was significantly better in those who were treated by induction chemotherapy (p = 0.04). CONCLUSION: Patients with squamous cell carcinoma treated on the CT + RT arm had a significant reduction of first DM other than brain, but there was difference in survival. Survival favored CT + RT in nonsquamous carcinoma despite similar failure patterns. Reasons for improved survival with CT + RT in NSCLC are not yet available.

Adenocarcinoma↗
PubMed1997

Three-dimensional reconstruction of aqueous channels in human trabecular meshwork using light microscopy and confocal microscopy.

Conventional two-dimensional imaging of the trabecular meshwork (TM) provides limited information about the size, shape, and interconnection of the aqueous channels within the meshwork. Understanding the three-dimensional (3-D) relationships of the channels within this tissue may give insight into its normal function and possible changes present in the eye disease glaucoma. The purpose of our study was to compare laser scanning confocal microscopy with standard 1 micron Araldite-embedded histologic sections for 3-D analysis of the trabecular meshwork. In addition, the study was done to determine whether computerized 3-D reconstruction could isolate the fluid spaces of the trabecular meshwork and determine the size of interconnections between the fluid spaces. Confocal microscopy appears comparable to 1 micron Araldite-embedded tissue sections and has the advantage of inherent registration of the serial tissue sections. Three-dimensional reconstruction allowed the isolation of the fluid spaces within the trabecular meshwork and revealed the presence of numerous interconnections between larger fluid spaces. The distribution of these interconnections was randomly arranged, with no predilection for specific regions within the trabecular meshwork. This distribution of constrictions and "expansion chambers" may provide a clue to the mechanism by which subtle histologic changes are associated with increased ocular pressure in glaucoma.

Aqueous Humor↗
PubMed1997

Soluble E-selectin in cancer patients as a marker of the therapeutic efficacy of CM101, a tumor-inhibiting anti-neovascularization agent, evaluated in phase I clinical trail.

A polysaccharide toxin, GBS toxin, is produced by group B Streptococcus (GBS) isolates from neonates who died of "early-onset disease". GBS toxin, named CM101 in the clinic, was hypothesized, on the basis of our previous in vivo studies, to induce inflammation in pulmonary neovasculature in neonates by cross-linking of embryonic receptors still expressed after birth and in tumor neovasculature in adults. Immunohisto chemical in vitro analysis of human biopsies showed that tumor neovasculature is indeed a binding site for CM101. In vivo studies in mice have demonstrated that CM101 induced inflammatory responses in neoplastic tumor neovasculature causing inhibition of tumor growth and tumor cell necrosis. These experimental observations warranted a phase I clinical trial for CM101 as an anti-neovascularization agent in human cancer therapy. Cancer patients received one cycle of therapy consisting of three treatments during 1 week. CM101 was administered over 15 min by i.v. infusion. Dosages of 7.5 micrograms/kg (1 U/kg), n = 3; 15 micrograms/kg (2 U/kg), n = 6; 24.75 micrograms/kg (3.3 U/kg), n = 3; and 37.5 micrograms/kg (5 U/kg), n = 3 were used. Enzyme-linked immunosorbent sandwich assays (ELISA) of the patients sera showed a marked elevation of soluble E-selectin with a peak concentration observed at 8-12 h after each CM101 infusion. The average baseline value for soluble E-selectin prior to the first treatment was 97.3 +/- 23.4 ng/ml (mean +/- SEM, n = 15) and the average peak level at 8 h was 441.6 +/- 62.4 (mean +/- SEM, n = 15; P < 0.001). Subsequent treatments gave average maximum soluble E-selectin levels again at 8 h of 466.9 +/- 87.6 and 412.0 +/- 67.8 ng/ml, for treatments 2 and 3 respectively. Baseline values for treatments 2 and 3 were 192.3 +/- 26.4 and 226.4 +/- 26.1 ng/ml respectively (p < 0.01 versus treatment 1). Out of 15 patients, 5 showed tumor reduction or stabilization and were given additional cycles of therapy. CM101 induced an increase in soluble E-selectin levels, which remained elevated over baseline at the start of the following treatment cycles. The baseline remained elevated for several weeks after the final treatment, i.e., P < 0.01 for levels before treatment 1 compared to those at week 4 after treatment. Elevated soluble E-selectin is considered proof of endothelial engagement in an inflammatory process. Our data support the contention that the inflammatory response observed in these cancer patients is targeting the tumor neovasculature and that measurement of soluble E-selectin levels in patients treated with CM101 can provide important information on the magnitude of CM101-mediated neovascular endothelial activation and tumor cell damage in cancer of endothelial origin, or cancer with a major neo-angiogenic component.

Adult↗
PubMed1997

Trabecular meshwork phagocytosis in glaucomatous eyes.

Trabecular meshwork cells are actively phagocytic and may function to keep the drainage pathways free of cellular debris, pigment and other material. A decrease in phagocytic capacity has been proposed in the pathogenesis of glaucoma. This study was performed to compare the phagocytic capability of the human trabecular meshwork in glaucomatous and normal human eyes. The anterior segments of 6 donors with glaucoma (primary open-angle glaucoma, POAG: 5 donors; pseudoexfoliative glaucoma, PEX: 1 donor) and 6 normal donors were placed in perfusion organ culture. During the final 24 h of culture, latex microspheres, labeled with FITC and coated with antibodies, were perfused into the anterior segments. Eyes were then fixed, the trabecular meshworks were treated with a rhodamine-labeled secondary antibody, sectioned and the number of ingested beads determined with the laser scanning confocal microscope. Nuclei were quantitated and used to calculate the phagocytic index of each eye (number of ingested beads/number of nuclei). Anterior segments of glaucomatous donors were cultured for 1-3 days, as a preliminary culture study had revealed that culture of glaucomatous anterior segments is successful in only 50% when cultured for 21 days. Specimens of normal donors were cultured for 21 days. Ingested beads appeared green and could be differentiated from noningested beads, which appeared red, using appropriate wavelengths of the laser. Bead ingestion was confirmed with electron microscopy and the use of a secondary antibody labeled with horseradish peroxidase. Ingestion rates appeared similar among all three groups of eyes: POAG, 3.8 beads/cell; PEX, 3.3 beads/cell; normal, 3.5 beads/ cell. No evidence of significant migration or loss of trabecular cells was noted. Cell counts were not significantly different: POAG, 127 +/- 40 cells/section; normals, 136 +/- 49 cells/section. In conclusion, the phagocytic ability of the trabecular meshwork appears similar between eyes with POAG and normal eyes in perfusion organ culture. Cell loss after phagocytosis was not observed in these single-exposure experiments.

Aged↗
PubMed1997

Paclitaxel, 5-fluorouracil, and folinic acid in metastatic breast cancer: BRE-26, a phase II trial.

5-Fluorouracil plus folinic acid and paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) are effective salvage therapies for metastatic breast cancer patients. Paclitaxel and 5-fluorouracil have additive cytotoxicity in MCF-7 cell lines. We performed a phase II trial of paclitaxel 175 mg/m2 over 3 hours on day I followed by folinic acid 300 mg over 1 hour before 5-fluorouracil 350 mg/m2 on days 1 to 3 every 28 days (TFL) in women with metastatic breast cancer. Analysis is reported on 37 patients with a minimum of 6 months follow-up who received a total of 192 cycles of TFL: nine cycles (5%) were associated with grade 3/4 neutropenia requiring hospitalization; seven (4%) cycles in two patients required granulocyte colony-stimulating factor due to neutropenia; no patient required platelet transfusions. Grade 3/4 nonhematologic toxicities were uncommon. Among the 34 patients evaluable for response, there were three complete responses (9%) and 18 partial responses (53%) for an overall response rate of 62%. Of the 19 evaluable patients with prior doxorubicin exposure, 11 (58%) responded compared with nine of 15 (60%) without prior doxorubicin. Plasma paclitaxel concentrations were measured at the completion of paclitaxel infusion and at 24 hours in 19 patients. TFL is an active, well-tolerated regimen in metastatic breast cancer.

Adult↗
PubMed1997

Rhodococcus equi pneumonia.

Corynebacterium equi is a pleomorphic gram-positive rod that was first isolated in 1923 by Magnusson, and is the cause of suppurative broncho-pneumonia in foals. The organism, now know as Rhodococcus equi, is ubiquitous in nature and is increasingly recognized as pathogenic, particularly in the immunocompromised population. Cavitary pneumonia clinically resembling Mycobacterium tuberculosis is the most common manifestation of R equi disease, but extrapulmonary infections are seen as well. Long term treatment with intracellularly active antimicrobial agents is required.

Actinomycetales Infections↗
PubMed1997

Severity of optic nerve damage in eyes with POAG is correlated with changes in the trabecular meshwork.

PURPOSE: We wished to determine whether eyes with primary open-angle glaucoma (POAG) and differing severity of optic nerve damage also have differences in severity of trabecular meshwork changes. METHODS: The trabecular meshwork and optic nerve from 26 eyes (14 donors) with the clinical diagnosis of POAG were studied. Severity of disease ranged from increased intraocular pressure (IOP) without damage to eyes with severe visual field loss. Optic nerve cross-sections were examined with light microscopy, and axonal counts were determined. We studied the trabecular meshwork around the circumference of each eye, examining sections from each quadrant with light and transmission electron microscopy. Morphometric measurements were made of the components of the cribriform region and statistically correlated with the axonal counts by the Pearson correlation coefficient. RESULTS: In eyes with advanced POAG, as determined by visual field loss, measurements of structures in the cribriform region of the trabecular meshwork and axon counts were in the same range as those reported previously in POAG. Axon counts showed a significant negative correlation with the amount of sheath-derived (SD) plaque material in the cribriform region: eyes with lower axon counts had larger amounts of SD plaques. Six eyes from four donors with increased pressure but no clinical signs of optic nerve damage showed no changes in axon counts and no increase in plaque material. CONCLUSIONS: Increasing severity of optic nerve damage in POAG is accompanied by an increase in the amount of SD plaque material in the trabecular meshwork.

Aged↗
PubMed1997

Treatment of small cell lung cancer.

Small cell lung cancer is an extremely virulent disease that tends to present at an advanced stage and may secrete multiple hormones and neural markers. In addition to the usual symptoms of advanced lung cancer, it may also present with a paraneoplastic syndrome. Unlike non-small cell lung cancer, small cell lung cancer is nearly always considered a systemic disease at the time of its discovery and, as a result, chemotherapy remains the cornerstone of treatment. Radiation is also used in most cases in which the disease is limited to the chest. Surgery is reserved for the very small subgroup of patients who present with an isolated mass and no evidence of distant or nodal spread. However, for the vast majority of patients who present with advanced disease, death may come as early as several weeks if they are not treated. With appropriate therapy the majority of these patients can expect to achieve remission and a significant prolongation of life. Long-term cures remain rare.

Antineoplastic Agents↗