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D H Johnson

Publications and source records attributed to D H Johnson.

At least 73 records · Page 4Linked to original sources
PubMed2000

Recombinant TIGR/MYOC increases outflow resistance in the human anterior segment.

PURPOSE: To determine the effect of human recombinant TIGR/myocilin (MYOC) protein on outflow resistance in the human anterior segment. METHODS: A cDNA for MYOC was inserted into a bacterial expression system and purified with nickel ion affinity chromatography. The anterior segments of 12 pairs of human eyes were placed in perfusion organ culture. One eye received an anterior chamber exchange with partially purified recombinant MYOC (25 microgram), whereas the other eye received either heat-denatured recombinant MYOC (25 microgram), partially purified ss-galactosidase (25 or 250 microgram), or partially purified control proteins isolated from a null expression lysate (25 microgram). Eyes were fixed up to 72 hours after infusion, and immunohistochemistry was performed using anti-MYOC polyclonal antibody. RESULTS: Recombinant MYOC caused an increase in IOP over 12 hours, increasing outflow resistance 94%, whereas the fellow eye infused with null expression sample increased 12% (n = 7; P = 0.0005). When compared with recombinant MYOC, neither heat-denatured MYOC, recombinant ss-galactosidase, bovine serum albumin, nor fetal calf serum caused an increase in outflow resistance. MYOC IOP remained above baseline levels for 48 to 72 hours. Immunohistochemistry results confirmed the presence of recombinant MYOC in the trabecular meshwork. CONCLUSIONS: Recombinant MYOC increased outflow resistance in human anterior segments, whereas control proteins did not. MYOC may increase outflow resistance by specific interactions within the trabecular meshwork.

Aged↗
PubMed2000

Implications for improved high-dose methotrexate therapeutic effects in cultured human breast cancer and bone marrow cells.

The cytotoxicity of high-dose methotrexate (MTX), 10 and 100 microM, and 5-fluorouracil (5-FU) combinations is independent of sequence in human MDA-MB-436 breast carcinoma cells. The growth inhibitory effects of 10 and 100 microM MTX are 22.54+/-1.56% and 16.20+/-0.74%, respectively, of the control rate. When the MTX and 5-FU concentrations are 10 microM, antiproliferative effects of MTX 2 hr before 5-FU (MTX/5-FU) and 5-FU 2 h before MTX (5-FU/MTX) are 25.17+/-1.23% and 25.60+/-1.28% of the control rate, respectively. The percentage of control rates for 5-FU alone is 94.89+/-1.35%. The growth rates of MDA-MB-436 cells in 100 microM MTX and 10 microM 5-FU are 15.19+/-0.62% (MTX/5-FU) and 16.53+/-0.85% (5-FU/MTX) of the control rate. The growth of cancer cells in the presence of 5-FU alone is 93.82+/-1.69% of the control rate. A comparison of the cell-killing effects of MTX and the nonpolyglutamable antifolate trimetrexate (TMQ) alone and in combination with 5-FU was performed to indirectly explore the role of polyglutamylation in breast cancer and bone marrow cells. The comparisons were made in equitoxic concentrations (10 microM) of MTX and TMQ and the time of exposure was the same. The inhibitory effects of TMQ, TMQ/5-FU, and 5-FU/TMQ in breast cancer cells were identical, but significantly less than MTX, MTX/5-FU, and 5-FU/MTX. The interaction between TMQ and MTX, TMQ/5-FU and MTX/5-FU, and 5-FU/TMQ and 5-FU/MTX was quantitatively similar in bone marrow. (Significant protection occurred in bone marrow cells exposed to 5-FU/TMQ and 5-FU/MTX.) Because the effects of 5-FU/MTX and 5-FU/TMQ on bone marrow were the same, it is unlikely that polyglutamylation plays a significant role in the protective effects of 5-FU. However, the greater inhibitory effect of MTX or MTX and 5-FU combinations, when compared with TMQ or TMQ and 5-FU, suggests that polyglutamylation of MTX may contribute to the cytotoxicity of this antifolate to breast cancer cells. Hence, these studies suggest that a priming and nontoxic dose of 5-FU before high-dose MTX sustains MTX cytotoxicity in breast cancer and protects against MTX toxicity to bone marrow progenitor cells.

Antimetabolites, Antineoplastic↗
PubMed1999

National survey on prophylactic cranial irradiation: differences in practice patterns between medical and radiation oncologists.

PURPOSE: Prophylactic cranial irradiation (PCI) in the treatment of small cell lung cancer (SCLC) patients remains controversial in the oncology community because of its potential for long-term toxicity and unproven survival benefit in randomized trials. A national survey of 9176 oncologists was conducted to characterize the use of PCI with regard to physician demographics, patient characteristics, and oncologists' beliefs. METHODS: Data was collected via a questionnaire letter survey. Biographical data, treatment patterns, and clinical impressions were analyzed by the generalized linear model and generalized estimating equations method. RESULTS: There were 1231 responders overall (13.4% of those surveyed), including 628 (51%) radiation oncologists (RO), 587 (48%) medical oncologists (MO), 8 (0.6%) surgical oncologists, and 8 (0.6%) from other oncology subspecialties. Of respondents, 74% overall recommend PCI in limited-stage patients, including 65% of MO and 82% RO (p = 0.001). Of responders who recommend PCI in limited-stage patients, 67% do so only after complete response to initial therapy. Only 30% of respondents recommend PCI for extensive-stage SCLC patients (p = 0.001), and 94% of these recommend PCI only when those patients have a complete response after initial therapy. Interestingly, 38% of responding MO feel that PCI improves survival of limited-stage patients, but only 11% believe PCI improves quality of life. Of the RO, 48% believe PCI improves survival in limited-stage SCLC, and 36% feel PCI improves quality of life (p < 0.05 and p < 0.01, respectively). MO responders believe PCI causes late neurological sequelae more often than do RO responders (95% vs. 84%, p < 0.05), with impaired memory (37%), chronic fatigue (19%), and loss of motivation (13%) as most commonly seen side effects. Only 1.5% overall, however, routinely obtain neuropsychiatric testing in PCI patients, and 42% overall never obtain them. CONCLUSION: Results confirm that oncologic subspecialists have statistically significant differences in opinion regarding the use of PCI. However, these differences may not translate into large differences in clinical practice. Most oncologists continue to recommend PCI in limited-stage SCLC patients, despite many believing PCI may not provide a survival advantage nor improve quality of life.

Brain Neoplasms↗
PubMed1999

Twice-daily compared with once-daily thoracic radiotherapy in limited small-cell lung cancer treated concurrently with cisplatin and etoposide.

BACKGROUND: For small-cell lung cancer confined to one hemithorax (limited small-cell lung cancer), thoracic radiotherapy improves survival, but the best ways of integrating chemotherapy and thoracic radiotherapy remain unsettled. Twice-daily accelerated thoracic radiotherapy has potential advantages over once-daily radiotherapy. METHODS: We studied 417 patients with limited small-cell lung cancer. All the patients received four 21-day cycles of cisplatin plus etoposide. We randomly assigned these patients to receive a total of 45 Gy of concurrent thoracic radiotherapy, given either twice daily over a three-week period or once daily over a period of five weeks. RESULTS: Twice-daily treatment beginning with the first cycle of chemotherapy significantly improved survival as compared with concurrent once-daily radiotherapy (P=0.04 by the log-rank test). After a median follow-up of almost 8 years, the median survival was 19 months for the once-daily group and 23 months for the twice-daily group. The survival rates for patients receiving once-daily radiotherapy were 41 percent at two years and 16 percent at five years. For patients receiving twice-daily radiotherapy, the survival rates were 47 percent at two years and 26 percent at five years. Grade 3 esophagitis was significantly more frequent with twice-daily thoracic radiotherapy, occurring in 27 percent of patients, as compared with 11 percent in the once-daily group (P<0.001). CONCLUSIONS: Four cycles of cisplatin plus etoposide and a course of radiotherapy (45 Gy, given either once or twice daily) beginning with cycle 1 of the chemotherapy resulted in overall two- and five-year survival rates of 44 percent and 23 percent, a considerable improvement in survival rates over previous results in patients with limited small-cell lung cancer.

Adult↗
PubMed1999

Probability of filtration surgery in patients with open-angle glaucoma.

OBJECTIVE: To investigate the probability of undergoing filtration surgery in either 1 or both eyes in patients in whom open-angle glaucoma was newly diagnosed. METHODS AND DESIGN: A retrospective community-based study of 295 residents of Olmsted County, Minnesota, in whom open-angle glaucoma was newly diagnosed between January 1, 1965, and December 31, 1980, was performed. Kaplan-Meier methods were used to estimate the cumulative probability of undergoing filtration surgery during a 20-year period. RESULTS: At 20 years of follow-up, the Kaplan-Meier cumulative probability of undergoing filtration surgery in at least 1 eye was estimated to be 23% (95% confidence interval, 16%-30%), and in both eyes the estimate was 12% (95% confidence interval, 6%-17%). Patients with optic nerve damage at the time of diagnosis were more likely to undergo surgery than patients with elevated intraocular pressure but no damage (1 eye, 39% vs 15%; both eyes, 27% vs 5%). CONCLUSION: This retrospective study of a white population newly diagnosed as having and treated for open-angle glaucoma indicates that while most patients did not undergo filtration surgery in the course of glaucoma therapy, at least one third of those with glaucomatous damage at the time of diagnosis underwent filtration surgery.

Aged↗
PubMed1999

Systemic thermal injury in anesthetized rabbits causes early pulmonary vascular injury that is not ablated by lazaroids.

PURPOSE: To study the effects of a systemic thermal injury on the pulmonary vasculature with and without inhibitors of lipid peroxidation (U74389G). METHODS: In a prospective, placebo control, randomized, and blinded multi-group study, burn shock was induced by scalding thermal injury (65C) to 35% body surface area in rabbits (n = 28). Hemodynamics and gas exchange were followed for 240 min post burn in four groups: No Burn, Burn-Control, Burn-U74 (10 mg.Kg-1 U74389G), No Burn-U74 (10 mg.Kg-1 U74389G). RESULTS: Scald resulted in early pulmonary injury as measured by increased pulmonary vascular resistance in the pooled Burn group compared with the No Burn groups (942 +/- 358 vs 605 +/- 255 dynes.sec-1.cm-5 respectively, P < 0.05). These pulmonary changes were associated with alveolar sequestration of leukocytes (4.8 +/- 2.9 vs 17.7 +/- 6.0 cells x 10(9).L-1, P < 0.05) in the No Burn and Burn groups respectively. Histological evidence of decreased neutrophil sequestration after scald injury was present in U74 treated animals (3+ vs 2+, P < 0.05 in the Burn and No Burn groups respectively and 2+ vs 2+, P > 0.05 in the Burn-U74 and No Burn-U74 groups respectively) although bronchial alveolar lavage still demonstrated neutrophil sequestration (5.3 +/- 2.5 vs 12.2 +/- 3.3 cell 10(9).L-1, P < 0.05 in No Burn-U74 and Burn-U74 groups respectively). Similarly, circulating white blood cells were increased in the Burn group but not Burn-U74 group four hours post burn. The increase in pulmonary vascular resistance after burn was not altered by administration of U74. CONCLUSIONS: Systemic burn results in early pulmonary vascular changes associated with leukocyte sequestration. After scald injury administration of lazaroids (U744389G) did not lessen pulmonary vascular resistance changes but did reduce neutrophil sequestration.

Analysis of Variance↗
PubMed1999

Tourniquet inflation during arthroscopic knee ligament surgery does not increase postoperative pain.

PURPOSE: A double-blind clinical trial was conducted to determine the effect of inflation of a thigh tourniquet during anterior cruciate ligament repair on arthroscopic visibility, duration of procedure, postoperative pain and opioid consumption. METHODS: Thirty patients were randomly allocated into two groups; Group I had the thigh tourniquet inflated during surgery whereas the tourniquet was not inflated in Group II patients. All patients received standardized general anesthesia and postoperative pain management. Supplemental analgesia was provided with i.v. morphine via a patient-controlled analgesia (PCA) apparatus. Verbal pain rating scores (0-10) were obtained after surgery. RESULTS: Arthroscopic visibility was impaired in Group II patients (P < 0.0001), but this was ameliorated by increased irrigation flow or addition of epinephrine. Duration of surgery was similar in both groups. There was no difference between groups in postoperative morphine consumption (9.8 +/- 7.1 mg in Group I vs 11.4 +/- 10.2 mg in Group II) or in postoperative pain scores between groups. CONCLUSION: Inflation of a thigh tourniquet did not result in increased pain or opioid consumption after arthroscopic ACL surgery. Arthroscopic visibility was somewhat impaired in some patients without the use of tourniquet. Finally, the duration of the surgical procedure was not increased in patients where the tourniquet was not inflated during the ACL repair.

Adult↗
PubMed1999

Phase II study of irinotecan plus cisplatin in patients with advanced non-small-cell lung cancer.

PURPOSE: To evaluate the antitumor efficacy and safety of a combination of irinotecan (CPT-11) and cisplatin in patients with inoperable non-small-cell lung cancer (NSCLC). A secondary objective was to characterize the pharmacokinetics and pharmacodynamics of CPT-11 and its active metabolite, SN-38. PATIENTS AND METHODS: Patients with stage IIIB or IV NSCLC were treated with repeated 4-week courses comprising CPT-11 (60 mg/m(2)) administered on days 1, 8, and 15, and a single dose of cisplatin (80 mg/m(2)) after CPT-11 administration on day 1. RESULTS: Fifty-two patients were enrolled, including 33 men and 19 women. The median age was 61 years (range, 29 to 79 years). Southwest Oncology Group performance status was 0 in 12 patients, 1 in 32 patients, and 2 in eight patients. Eleven and 41 patients had stage IIIB and IV disease, respectively. Objective responses occurred in 28.8% of patients (15 of 52; 95% confidence interval, 16.5% to 41.2%). The median survival duration was 9.9 months (range, 1.6 to 30.8 months). The 1-year survival rate was 37%. Grade 3/4 adverse events consisted primarily of nausea (32. 7% ) or vomiting (13.5%), late-onset diarrhea (17.3%), and neutropenia (46.1%). The study design led to preferential modification of CPT-11 doses, resulting in CPT-11 dose attenuations to < or = 40 mg/m(2) in the majority of patients (31 of 52; 60%), whereas dose reductions of cisplatin were uncommon. CPT-11 pharmacokinetic parameters were comparable to those reported previously in single-agent studies. CONCLUSION: CPT-11/cisplatin is an active combination regimen with manageable toxicity in the therapy of stage IIIB/IV NSCLC. Future studies should be designed with schedules and dose modification provisions that avoid unnecessary CPT-11 dose reductions to exploit more directly the therapeutic synergy of these agents.

Adult↗
PubMed1999

Management of small cell lung cancer: current state of the art.

Small cell lung cancer (SCLC) is a common malignancy that is rapidly fatal if left untreated, with most patients surviving < 6 months. Currently, patients with SCLC are treated with chemotherapy with or without thoracic radiotherapy. Randomized trials have demonstrated the superiority of multiagent regimens over single-agent therapies, with the combination of cisplatin and etoposide being the initial regimen of choice for most patients, regardless of stage at presentation. Dose escalation, weekly chemotherapy, alternating noncross-resistant chemotherapy, and maintenance chemotherapy have been evaluated in SCLC, with no convincing data to date demonstrating an advantage for these strategies over conventional treatment strategies. Second-line therapy may be effective in selected patients, depending on the interval between primary treatment and recurrence, response to primary therapy, and the agents used for initial treatment. Radiotherapy is generally accepted as an essential component of optimal management of limited-stage disease, although sequencing, timing, fractionation, dose, and field size remain less than adequately defined. Finally, the routine use of prophylactic cranial irradiation remains controversial, and currently should be reserved for patients in complete remission.

Antineoplastic Agents↗
PubMed1999

Treatment strategies for metastatic non small-cell lung cancer.

This review article provides evidence to support the use of chemotherapy for non small-cell lung cancer (NSCLC). Chemotherapy plays an important role in the management of advanced NSCLC. Chemotherapy offers symptom palliation, modest but real survival benefits and improves quality of life. The survival benefits achieved with newer drug regimens offer chemotherapy as a strategy for the treatment of NSCLC patients with good performance, no medical or psychological contraindications.

Journal Article↗
PubMed1999

Docetaxel and cisplatin in patients with advanced non small-cell lung cancer (NSCLC): a multicenter phase II trial.

We examined the safety and efficacy of the docetaxel/cisplatin combination in patients with advanced, previously untreated NSCLC and evaluated changes in quality of life over time. Docetaxel was administered before cisplatin (both 75 mg/m2, 1-hour infusions) every 3 weeks to 47 patients with stage IIIB or stage IV NSCLC. Patients also received premedication of oral dexamethasone. The median age (range) of patients was 62 (45-78) years and 26 patients (55.3%) had adenocarcinoma. Of the 40 patients evaluable for response, one achieved a complete response and 14 had partial responses; the response rate was 37.5% (95% confidence intervals; 22.5, 52.5). In the intent-to-treat population the overall response rate was 31.9%. Time to response ranged from 3 to 20 weeks, and the median duration of response was 34.6 weeks. Median survival and median time to progression were 11.3 months and 18.9 weeks, respectively. One-year survival was 40%. Grade 3 or 4 neutropenia and febrile neutropenia were observed in 74.4% and 12.8% of patients, respectively. Severe asthenia was seen in 14.9% of patients. Other grade 3 or 4 toxicities included nausea (eight patients), vomiting (five), neurosensory effects (six), neuromotor effects (five), diarrhea (four), and infection (three). There was an improvement in emotional well-being; however, the overall quality of life score did not change with treatment. Docetaxel administered in combination with cisplatin is an active regimen in patients with NSCLC. This regimen of docetaxel (75 mg/m2) and cisplatin (75 mg/m2) repeated at 3-week intervals is being evaluated in an ongoing Eastern Cooperative Oncology Group (ECOG) randomized study in patients with advanced and metastatic NSCLC.

Journal Article↗
PubMed1999

Prevention of recurrent cerebral ischemic events in patients with patent foramen ovale and cryptogenic strokes or transient ischemic attacks.

BACKGROUND: Patent foramen ovale (PFO) is found in up to 50% of patients less than 55 years of age who have had a stroke. Therapeutic options include no therapy, antiplatelet therapy, warfarin and surgical closure of the PFO. OBJECTIVES: To determine the relative and attributable risks of PFO for recurrent cerebral ischemic events in young patients with stroke or transient ischemic attacks. The predictors of recurrent cerebral ischemic events and the effects of different therapies on recurrence rates were sought. DESIGN: Follow-up of a retrospective cohort of patients with cryptogenic stroke or transient ischemic attacks identified from an echocardiography database. SETTING: University-based regional neurology referral centre. PATIENTS: Consecutive group of 90 patients less than 60 years of age who underwent transesophageal echocardiography following a cryptogenic transient ischemic attack (TIA) or stroke (cerebrovascular accident [CVA]) between 1991 and 1997. INTERVENTIONS: Structured telephone interviews and chart reviews. RESULTS: Fifty-two patients had a PFO, and 38 patients did not have a PFO. During a mean follow-up of 46 months, 19 recurrent cerebral ischemic events (12 TIA and seven CVA) occurred in 14 patients with PFO, and eight recurrent events (three TIA and five CVA) occurred in six patients without PFO. The recurrence rates were 12% and 5%/patient/year in the PFO and control groups, respectively, for a crude recurrence rate ratio of 2.39 (95% CI 1.01 to 6.32, P < 0.03). The attributable risk of PFO in recurrent neurological events was 7%/patient/year. In a Cox regression model, predictors of recurrent neurological events were presence of PFO (hazard ratio 5.27, 95% CI 1.58 to 17.6, P < 0.007), history of migraine (hazard ratio 4.54, 95% CI 1.11 to 18.52, P < 0.035), hypertension requiring therapy (hazard ratio 3.5, 95% CI 1.33 to 9.01, P < 0.01), and antiplatelet or no therapy instead of warfarin therapy (hazard ratio 2.88, 95% CI 1.11 to 8.7, P < 0.04). Fourteen patients underwent surgical closure of PFO; there were no neurological recurrences during a mean follow-up of 43 months (crude incidence rate difference 12%/patient/year, 95% CI 6.6 to 17.9, P < 0.02). CONCLUSIONS: Patients with PFO had a significantly higher rate of recurrent cerebral ischemic events than those without PFO. Surgical PFO closure prevented any recurrences during a mean follow-up of 43 months. Warfarin was better than antiplatelet therapy or no therapy in preventing recurrences.

Adolescent↗
PubMed1999

Concurrent paclitaxel and thoracic irradiation for locally advanced esophageal cancer.

Esophageal cancer is a major cause of morbidity and mortality worldwide. Although patients often present with apparently resectable disease, systemic spread frequently occurs before the development of symptoms and detection of tumor. The use of combined chemoradiation therapy, particularly before resection, appears to prolong survival and increase cure rates in certain histologic subtypes. Four randomized phase III trials compared preoperative chemoradiotherapy plus surgery with surgery alone. In trials including only patients with squamous histology, no improvement in survival was observed with preoperative chemoradiation therapy; however, in a trial including only patients with adenocarcinoma histology, improved median and overall survival were observed. Paclitaxel has been evaluated as a single agent in a phase II trial in previously untreated patients with locally advanced unresectable or metastatic esophageal cancer; the overall response rate was 32% and median survival was 13.2 months. Paclitaxel-based combinations also have been evaluated in esophageal cancer; particularly encouraging preliminary results have been achieved with paclitaxel/cisplatin/5-fluorouracil. Because paclitaxel is a potent radiosensitizer, it also has been evaluated in combination with radiation therapy for esophageal and other thoracic cancers, alone and in combination with other chemotherapeutic agents. Preliminary results suggest that neoadjuvant therapy with paclitaxel-based combinations (including 5-fluorouracil and cisplatin) and radiation is highly active, with variable toxicity. A goal of future trials is to assess paclitaxel-based combined modality therapy in combination with other new chemotherapeutic agents.

Antineoplastic Agents, Phytogenic↗
PubMed1999

Modulation of myocilin/TIGR expression in human trabecular meshwork.

PURPOSE: To study factors that modulate myocilin/trabecular meshwork inducible glucocorticoid response protein (TIGR) mRNA expression in human trabecular meshwork (TM). METHODS: mRNA from fresh TM of four human donors, from perfused anterior segment organ cultured TM of three donors, and from four primary TM cell lines of different donors was isolated. The full length cDNA of myocilin/TIGR was cloned from TM mRNA using a polymerase chain reaction approach and used as probe for northern blot analysis hybridization. Trabecular meshwork cell cultures were treated with transforming growth factor (TGF)-beta1 (1 ng/ml), dexamethasone (10(-7) M), and mechanical stretch (10%). RESULTS: mRNA for myocilin/TIGR could be readily detected by northern blot analysis hybridization in 2 to 3 microg of total RNA from all fresh and all organ-cultured TM samples. In contrast, no mRNA for myocilin/TIGR could be detected in 20 microg of total RNA isolated from three different primary TM cell lines. Only one TM cell line had a baseline expression of myocilin/TIGR, which was 35- to 55-fold lower than that of fresh or organ-cultured TM samples. Treatment of TM cell cultures with dexamethasone for 1 day markedly increased expression of myocilin/TIGR mRNA, an effect that was even more pronounced after 3 days of treatment. Treatment with TGF-beta1 for 24 hours had no effect; however, after 3 and 12 days of treatment a 3.8- and 4-fold increase in myocilin/TIGR mRNA expression was observed. Expression of myocilin/TIGR mRNA was also increased after 10% mechanical stretch; however, in contrast to the effects of TGF-beta-1, this effect was observed much earlier (8-24 hours) after treatment. CONCLUSIONS: Dynamic mechanical stimuli maintain myocilin/TIGR expression in TM in situ and lack of these stimuli in monolayer cell cultures might be involved in downregulation of myocilin/TIGR expression.

Adult↗
PubMed1998

A phase II study of all-trans-retinoic acid plus cisplatin and etoposide in patients with extensive stage small cell lung carcinoma: an Eastern Cooperative Oncology Group Study.

BACKGROUND: The dysregulation of both myc gene expression and retinoid signaling pathways commonly occurs in small cell lung carcinoma (SCLC). Because preclinical data showed that all-trans-retinoic acid (RA) inhibited SCLC growth, altered myc expression, and blocked transition to a treatment-resistant phenotype, a Phase II trial was designed to determine the effects of the combination of RA, cisplatin, and etoposide in patients with SCLC. METHODS: Patients with untreated, extensive stage SCLC were treated with up to 8 cycles of cisplatin, 60 mg/m2, intravenously (i.v.) on Day 1 and etoposide, 120 mg/m2, i.v. on Days 1-3 in addition to up to 1 year of oral RA, 150 mg/m2/day. RESULTS: Of 22 assessable patients 1 had a complete response and 9 had a partial response, for an overall response rate of 45% (95% confidence interval, 24-68%). The median survival was 10.9 months and the 1-year survival was 41%. The median duration of chemotherapy was 6 cycles and the median duration of RA treatment was 2.8 months. Thirteen patients discontinued RA prematurely due to toxicity and only 4 responders were receiving RA at the time of recurrence. Toxicity-limiting RA treatment mainly was comprised of mucocutaneous changes and headaches. CONCLUSIONS: RA at a dose of 150 mg/m2/day was tolerated poorly in combination with cisplatin plus etoposide, leading to early discontinuation of RA in the majority of patients. The hematologic toxicity, response rate, and survival were similar to those associated with cisplatin and etoposide in prior trials. Further studies with more active and less toxic agents will be required to determine the role of retinoids in the treatment of SCLC.

Adult↗
PubMed1998

Protein analysis by membrane preconcentration-capillary electrophoresis: systematic evaluation of parameters affecting preconcentration and separation.

Fast and efficient analysis of proteins in physiological fluids is of great interest to researchers and clinicians alike. Capillary electrophoresis (CE) has proven to be a potentially valuable tool for the separation of proteins in specimens. However, a generally acknowledged drawback of this technique is the limited sample volumes which can be loaded onto the CE capillary which results in a poor concentration limit of detection. In addition, matrix components in samples may also interfere with separation and detection of analytes. Membrane preconcentration-CE (mPC-CE) has proved to be effective in overcoming these problems. In this report, we describe the systematic evaluation of parameters affecting on-line preconcentration/clean-up and separation of protein mixtures by mPC-CE. Method development was carried out with a standard mixture of proteins (lysozyme, myoglobin, carbonic anhydrase, and human serum albumin). First, using MALDI-TOF-MS, membrane materials with cation-exchange (R-SO3H) or hydrophobic (C2, C8, C18, SDB) characteristics were evaluated for their potential to retain proteins in mPC cartridges. Hydrophobic membranes were found most suitable for this application. Next, all mPC-CE analysis of protein samples were performed in polybrene coated capillaries and parameters affecting sample loading, washing and elution, such as the composition and volume of the elution solvent were investigated. Furthermore, to achieve optimal mPC-CE performance for the separation of protein mixtures parameters affecting postelution focusing and electrophoresis, including the composition of the background electrolyte and a trailing stacking buffer were varied. Optimal conditions for mPC-CE analysis of proteins using a C2 impregnated membrane preconcentration (mPC) cartridge were achieved with a background electrolyte of 5% acetic acid and 2 mM ammonium acetate, 60 nl of 80% acetonitrile in H2O as an elution solvent, and 60 nl of 0.5% ammonium hydroxide as a trailing stacking buffer. The developed method was used successfully to separate proteins in aqueous humor, which contains numerous proteins in a complex matrix of salts.

Aqueous Humor↗