Biomedical subjects

A Elias

Publications and source records attributed to A Elias.

At least 37 records · Page 2Linked to original sources

PubMed1999

Anti-Sa antibody is an accurate diagnostic and prognostic marker in adult rheumatoid arthritis.

OBJECTIVES: To evaluate in various groups of patients with chronic joint disease the sensitivity and specificity of anti-Sa antibody, recently described in sera from adults with rheumatoid arthritis (RA); and to determine the prognostic significance of anti-Sa in initial sera from patients with long standing RA with or without severe joint destruction. METHODS: Serum samples from 489 patients were included. Of these, 154 were collected from patients with RA attending 2 rheumatology units. Controls were 335 patients with a variety of inflammatory joint diseases other than RA. IgG anti-Sa was detected using an immunoblotting method with purified Sa antigen from human placenta extracts. All patients were tested for the following antibodies: rheumatoid factor (RF), anti-keratin antibody (AKA), antiperinuclear factor (APF), and anti-RA 33. HLA class II DRB alleles were also determined. RESULTS: Anti-Sa was detected in 39.8% of RA sera overall, 46.7% of sera from the long standing RA group, and 23.5% of sera from the recent onset RA group (p<0.01). In patients with long standing RA, statistically significant associations were found between the presence of anti-Sa and the following variables: RF (p<0.0001), AKA (p<0.0001), APF (p<0.00001), and HLA DRB1*04 or 01 (p<0.01). In contrast, no association was found with anti-RA33. Anti-Sa was positive in 11 adult controls (7.8%) and in 26 pediatric patients with juvenile chronic arthritis (22%). The specificity of anti-Sa for RA was 92.1% in adults with well characterized rheumatic diseases and 85.9% in adults and children together. Among patients with long standing RA, those with destructive disease were more likely to test positive for anti-Sa (66.6%) than those with nondestructive disease (22.2%) (p<0.0001). Comparisons with other serologic markers for RA demonstrated that anti-Sa was sensitive (68.4%) and was also the test with the highest specificity (79%), positive predictive value (75%), and negative predictive value (71%) for discriminating between patients who do and those that do not develop late severe radiographic damage. CONCLUSION: Immunoblot-detected IgG anti-Sa is a sensitive serologic marker for RA patients with severe radiographic damage.

Adult↗

PubMed1998

Genetic studies in Borrelia burgdorferi.

Borrelia burgdorferi, the agent of Lyme disease, has recently joined a growing number of micro-organisms for which the entire genomic sequence is known. Despite this wealth of information, little is known about the contribution of specific spirochetal components to the pathogenesis of Lyme disease or their function in the normal life cycle of the organism. This discrepancy is due in part to the lack of a well-developed genetic system in B. burgdorferi, which in turn can be attributed to its relatively recent isolation and the dissimilarity of Borrelia from other genetically tractable bacteria. We are interested in several plasmid-encoded gene products in B. burgdorferi that may play a role in sensing and adaptation to the different environments the spirochete encounters as it completes an infectious cycle between the tick vector and the mammalian host. We are developing genetic tools with which to test the roles of specific B. burgdorferi gene products in the transmission cycle in an animal model of Lyme disease. We have demonstrated targeted gene inactivation by allelic exchange, using the gyrBr gene encoding coumermycin-resistant topoisomerase as a selectable marker. Spirochetes are transformed by electroporation and coumermycin-resistant colonies are screened by PCR for allelic exchange at the targeted locus. We have successfully inactivated several genes of interest in the type strain B31. We are investigating the utility of additional antibiotic resistance genes as selectable markers in B. burgdorferi. Targeted gene inactivation is a powerful tool with which to investigate the role of particular proteins in the basic biology and virulence of a pathogenic microorganism. We have made significant advances in our ability to genetically manipulate B. burgdorferi in order to address these issues. However, the available methods are incomplete and far from routine. We are currently improving existing methods as well as developing additional genetic tools with which to augment genetic studies in B. burgdorferi.

Borrelia burgdorferi Group↗

PubMed1998

Growth of infectious and non-infectious B. burgdorferi at different salt concentrations.

Borrelia burgdorferi, the causative agent of Lyme disease, grows in vitro in modified Barbour-Stoenner-Kelly (BSK-H) medium. We have studied the effect of increased osmotic strength of culture media on growth of infectious and non-infectious B. burgdorferi strains B31 and N40. Relatively small increases in the NaCl concentration of the medium significantly inhibited growth in infectious as well as non-infectious strains. Growth of low passage, infectious clone B31-4a was more sensitive to increased NaCl concentrations than high passage, non-infectious clone B31-a. Growth of two infectious N40 strains, one low passage (N40-Lp) and one high passage (N40-P31) was more resistant to increased NaCl concentration than growth of infectious B31-4a. Osmotic strength is an important physical parameter for growth of B. burgdorferi in vitro and could influence its ability to adapt and to establish an infection within ticks and mammals.

Borrelia burgdorferi Group↗

PubMed1998

Neutropenic enterocolitis as a complication of high dose chemotherapy with stem cell rescue in patients with solid tumors: a case series with a review of the literature.

BACKGROUND: This case series with an accompanying review of the literature describes neutropenic enterocolitis as a complication of high dose chemotherapy with stem cell rescue in patients with solid tumors. METHODS: Neutropenic enterocolitis is documented in two patients undergoing autologous stem cell transplantation. A review of MEDLINE from 1970 to the present was performed to delineate the prior related disease settings in which this condition has been described. The nature of the clinical syndrome and controversies regarding management are discussed. RESULTS: The authors report two patients who each received autologous stem cell transplantation for the treatment of a solid tumor. Both patients presented with progressive abdominal pain, signs of peritoneal irritation on examination, and pneumatosis intestinalis. In the first case, the syndrome developed rapidly over several hours, requiring emergent surgical intervention during the period of postchemotherapy nadir. In the second case, the patient developed a slowly progressive clinical picture that was managed successfully with medical therapy alone. A review of the literature suggests that neutropenic enterocolitis arises due to drug-induced bowel wall mucosal injury followed by superinfection with colonic and opportunistic organisms. Surgical intervention potentially is beneficial in patients who develop an acute syndrome that is unresponsive to antibiotic and supportive therapy. Those patients who can be stabilized with medical management often will recover once reengraftment occurs. CONCLUSIONS: Neutropenic enterocolitis is described in two patients undergoing autologous stem cell transplantation for solid tumors. The management of this life-threatening complication is controversial and governed by the nature of the clinical presentation.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1998

Primary diffuse large B-cell lymphoma of the mediastinum: outcome following high-dose chemotherapy and autologous hematopoietic cell transplantation.

We performed a retrospective analysis of 35 patients with primary diffuse large B-cell lymphoma of the mediastinum treated with high-dose cyclophosphamide, carmustine, and etoposide (CBV) plus autologous hematopoietic cell transplantation to determine outcome and prognostic features for progression-free survival (PFS). Thirty-five patients with primary diffuse large B-cell lymphoma of the mediastinum in first response (complete remission [CR] or partial remission [PR]) with poor prognostic features, with primarily refractory disease, or with relapsed disease following conventional chemotherapy, were treated with CBV and autologous hematopoietic cell transplantation. PFS and overall survival were assessed by the Kaplan-Meier method. Patient characteristics before transplantation were examined by univariate analysis using the log-rank test and by Cox's proportional hazards regression analysis to determine predictors of PFS. Estimated 5-year PFS varied significantly with patient disease status at transplantation. Patients transplanted in first response had an estimated 5-year PFS rate of 83%, compared with 58% and 27% for primarily refractory and relapsed patients, respectively (P = .02). The strongest predictor of PFS was chemotherapy responsiveness immediately before transplantation. Patients with chemotherapy-responsive disease had a significantly greater PFS rate than patients with chemotherapy-nonresponsive disease (risk ratio, 3.60; 95% confidence interval [CI], 1.14 to 11.4). No other factors were found to be significant on univariate or multivariate analysis. Patients with primary diffuse large B-cell lymphoma of the mediastinum can achieve prolonged PFS following high-dose chemotherapy and autologous hematopoietic cell transplantation. Outcomes are strongly correlated with disease status (first response v refractory v relapsed) at transplantation and chemotherapy responsiveness immediately before transplantation.

Adolescent↗

PubMed1998

Transformation of the Lyme disease spirochete Borrelia burgdorferi with heterologous DNA.

Studies of the spirochete Borrelia burgdorferi have been hindered by the scarcity of genetic tools that can be used in these bacteria. For the first time, a method has been developed by which heterologous DNA (DNA without a naturally occurring B. burgdorferi homolog) can be introduced into and persistently maintained by B. burgdorferi. This technique uses integration of circular DNA into the bacterial genome via a single-crossover event. The ability to transform B. burgdorferi with heterologous DNA will now permit a wide range of experiments on the biology of these bacteria and their involvement in the many facets of Lyme disease.

Borrelia burgdorferi↗

PubMed1998

High-dose multimodality therapy with autologous stem-cell support for stage IIIB breast carcinoma.

PURPOSE: Women with locally unresectable and inflammatory breast carcinoma (IBC) have an approximately 30% 5-year disease-free survival (DFS) rate with conventional multimodality therapy. A short but dose-intensive multimodality phase II trial was designed in an attempt to improve outcome in stage IIIB disease. Mastectomy was performed after high-dose therapy to evaluate pathologic response to treatment. METHODS: Women with newly diagnosed disease received four 2-week cycles of doxorubicin 90 mg/m2 with granulocyte colony-stimulating factor (G-CSF), followed by cyclophosphamide 6,000 mg/m2, thiotepa 500 mg/m2, and carboplatin 800 mg/m2 (CTCb) with marrow and peripheral-blood progenitor cell (PBPC) support. Local therapy consisted of mastectomy and radiotherapy. Tamoxifen (5 years) was begun if the patient was estrogen receptor-positive (ER+). RESULTS: Fifty women (46 stage IIIB [91% IBC], four stage IIIA) entered the study and 47 are assessable. Ten had mastectomy before any systemic therapy (seven with pathologic IBC, three with residual tumor after mastectomy). Eighty percent received full-dose doxorubicin with 60% on schedule. Clinical response rates to induction were 15% complete response (CR), 5% very good partial response (VGPR), 59% partial response (PR), and 21% minor response (MR)/stable disease (SD). Mastectomy after CTCb in 37 patients showed a 14% pathologic CR rate, 29% microscopic foci in breast and/or axilla, and 57% gross tumor. Fifteen (32%) patients have relapsed (median, 17 months post-CTCb). The 30-month DFS is estimated at 64%. For those in pathologic CR, with microscopic, or with gross disease remaining after CTCb, the 30-month DFS is estimated at 100%, 70%, and 38%, respectively. Those with zero, one to three, or > or = four positive nodes at axillary dissection had a median DFS of 31, 18, and 13 months, respectively. CONCLUSION: This short but dose-intensive multimodality approach for stage IIIB breast carcinoma is feasible with encouraging results to date.

Adult↗

PubMed1998

Dose-intensive therapy in small cell lung cancer.

Basic to curative treatment for small cell lung cancer (SCLC) are the principles of dose response, combination chemotherapy, and combined-modality therapy. Theory and experimental and clinical data suggest that solid tumors recur, despite initially responding to chemotherapy due to drug resistance. Resistance to chemotherapy is potentially overcome by using 5- to 10-fold higher doses. To decrease the emergence of drug resistance, combinations of active non-cross-resistant agents are used. Hematopoietic stem cell support provides the opportunity to test dose response to the limits of organ tolerance. Dose-intensive therapy for lung cancer patients is complicated by the fact that this disease most often occurs in an older-aged population (median, 60 to 65 years) with underlying smoking-related comorbid disease, early metastatic spread, and enhanced risk of secondary smoking-related malignancies. In a phase II feasibility trial just activated, patients younger than 60 years of age with limited-stage SCLC are being treated with four cycles of cisplatin and etoposide and concurrent twice-daily chest radiotherapy to 45 Gy (150-cGy fractions). Those patients achieving complete or near-complete response will receive high-dose cyclophosphamide/cisplatin/ carmustine with autologous stem cell support. Upon recovery, prophylactic cranial irradiation will be given. Results could lead to a phase III trial testing the concept of dose intensification. This article reviews evidence for the contribution of dose intensification to response and survival in the treatment of SCLC, the adequacy of the clinical trial's design to address these relationships, and suggestions for future directions. The strategies of dose-intensive induction therapy, multicycle dose-intensive combination therapies, chest radiography, and stem cell purging trials will be discussed.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1998

[Treatment of deep venous thrombosis at home: evolution from ideas to medical practice].

The diagnosis of Deep Venous Thrombosis (DVT) by duplex ultrasound is absolutely possible out of specialized centers. Low Molecular Weight Heparins (LMWH) allow to obtain a greater efficacy and safety compared to Unfractionated Heparin (UFH). The control of LMWH is very reduced. Two studies have just been published on the topic of treatment of DVT at home. The group of patients treated at home with LMWH is not presenting more complications than the group of patients initially treated at the hospital with UFH. Nevertheless, these studies concern a very selective population of patients. Our center has been proceeding to a study for 4 years (1993-1997) in comparing the treatment at home of proximal DVT by LMWH then oral anticoagulant, to the initial treatment (10 days) in hospital by also using LMWH then oral anticoagulant. The first results show that there is no difference between both groups in terms of end-points: death, extension or recurrence of the thrombus, pulmonary embolism, bleeding. Therefore, the treatment of some type of proximal DVT is possible at home. Nevertheless, it is necessary to be very cautions as the population studied so far is a selected one. Etiologies of DVT are a constant obsessive fear. DVT or pulmonary embolism represents a real general disease which is going to progress along life. The intervention of a specialized center is always necessary. It is a work in team which must get the upper hand compared to an isolated medical action.

Adolescent↗

PubMed1998

The relationship between high-dose treatment and combination chemotherapy: the concept of summation dose intensity.

The most important variables for the clinical use of antitumor agents (AAs) are dose and combination chemotherapy. The objectives of this study were to analyze the relationship between these two variables and to propose a unified conceptual framework for the construct and interpretation of clinical trials. Definitions and variables with respect to dose include potency, therapeutic index, standard dose, efficacy, relative efficacy, dose-limiting toxicity (DLT), dose rate, dose density, dose intensity, and fractional dose intensity. Our overarching concept, that is, summation dose intensity (SDI), was calculated in several ways, depending upon the nature of the data, and included the relative efficacy method, the unit regimen method, and the high dose method. The SDI concept was then applied to disease categories and strategies to determine its usefulness and effectiveness in integrating dose and combinations. The tumors and settings were: mustargen-vincristine-procarbazine-prednisone in Hodgkin's disease, combination chemotherapy for acute lymphocytic leukemia in children, metastatic breast cancer including dose and combinations, selected other solid tumors, alternating chemotherapy, and high dose studies in the leukemias and lymphomas. SDI was effective in integrating and quantifying dose and combination chemotherapy. For classical AAs, the implication of SDI for the construct and analysis of clinical trials was emphasized. In addition to new drug development, emphasis should be given to reducing or eliminating DLTs, such as those of the marrow, now and, in the future, those of the gastrointestinal tract toxicity and other DLTs. The above was derived from and applies to the classical AAs. Whether they will apply to, with appropriate adjustment, agents with significantly different dose-response curves, such as biotherapeutics and hormonal agents, remains to be determined.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1997

Dose-intensive therapy in lung cancer.

Lung cancer is epidemic and lethal throughout the world. Overall survival is estimated to be 13% at 5 years despite treatment. The use of chemotherapy in small-cell lung cancer (SCLC) is established, but it is less active against non-SCLC (NSCLC). Since 98% of SCLC cases are associated with heavy smoking and present at a median age of 60-65 years, the application of dose-intensive therapy to lung cancer patients may be complicated by underlying smoking-related comorbidity and an enhanced risk for secondary smoking-related malignancies. The strategies of intensifying induction therapy, multicycle dose-intensive combination therapies, chest radiotherapy, and stem cell purging for both SCLC and NSCLC are discussed herein. Limited data regarding high-dose therapy for NSCLC have been reported. In SCLC, excellent and immediate palliation is achieved through the use of combination chemotherapy. However, by 2 years, only 20-40% of limited-disease-(LD) and < 5% of extensive-disease stage (ED) patients remain alive. Regimens developed using the many established agents produce similar short- and long-term outcomes, an observation that suggests that many of our systemic agents eradicate the same tumor subpopulation but fail to abolish a central core of tumor stem cells, presumably enriched for heterogeneous in vivo resistance mechanisms. The identification of these minimal residual tumor (MRT) cells and systematic evaluation of their biologic characteristics may guide strategies to target these cells specifically; such strategies may include modification of chemotherapy, tumor vaccination, or other forms of biologic therapy, such as replacement of RB, 3p, and/or p53 function; interference with autocrine or paracrine growth loops; or immunologic therapy [interleukin (IL)-2, IL-12, immunotoxins, and tumor vaccines], which would be most effective in the setting of MRT. To this end the detection of heterogeneity and analysis of patterns of coexpression of various markers form the thrust of our MRT detection program. At the Dana-Farber Cancer Institute and Beth Israel Hospital we performed stem-cell autografts in > 40 patients with LD SCLC and > 25 patients with ED SCLC who were in first response to conventional-dose therapy comprising high-dose combination alkylating agents. Approximately 80% of our patients were in or near complete response after initial chemotherapy. At a minimal follow-up of 23 months (to as long as 10 years) after completion of high-dose chemotherapy in our original trial, 52% of the patients remain disease-free. Of the ED or extrapulmonary patients, approximately 20% remain progression-free at > 2 years after high-dose therapy. Local regional recurrence represents about 50% of all relapses. Thus, the roles of thoracic radiation dose intensity and purification of stem-cell autografts are being evaluated in ongoing trials. It is hoped that a cooperative phase III trial testing the concept of dose intensification will begin soon.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1997

Autoantibodies predicting the outcome of rheumatoid arthritis: evaluation in two subsets of patients according to severity of radiographic damage.

OBJECTIVE: Autoantibodies such as rheumatoid factor (RF), antikeratin antibodies (AKA), antiperinuclear factor (APF), and anti-RA 33 antibodies are considered of value for the diagnosis of RA. The purpose of this study was to evaluate these autoantibodies as predictors of severe radiographic damage in rheumatoid arthritis (RA). PATIENTS AND METHODS: Eighty six patients with RA (70 women, 16 men) fulfilling 1987 ACR criteria were selected from a cohort of 469 patients followed up since the first year of RA onset because they could be divided in two groups according to the severity of the radiographic damage. These 86 patients had a mean (SD) disease duration of eight (four) years: 43 patients had severe radiographic damage (Larsen score > or = 2) and 43 had limited radiographic damage (Larsen score < 2). The two groups were matched by disease duration and sex. The following autoantibodies were looked for: RF, ANA, AKA, APF, and anti-RA 33 antibodies. In addition, HLA class II DR beta alleles and standard inflammatory parameters (erythrocyte sedimentation rate, C reactive protein) were determined. RESULTS: Patients with severe radiographic damage differed from those with limited radiographic damage in that they had higher RF (p = 0.01), APF (p < 0.02), and AKA (p = 0.001) titres. Stepwise regression analysis was done to calculate the odds ratios (OR) for each clinical and laboratory variable; only presence of cutaneous nodules (OR: 14.9; 95% CI: 7, 128), HLA DRB1*04 or DRB1*01 (OR: 7.53; 95% CI: 1.32, 42.9), AKA (OR: 3.11; 95%, CI: 0.58, 16.8), a high erythrocyte sedimentation rate (OR: 2.66; 95% CI: 0.60, 11.9), and a high C reactive protein value (OR: 7.4; 95% CI: 1.43, 38.1) were predictive of severe radiographic damage. CONCLUSION: These data suggest that the risk of severe radiographic damage in RA patients is higher when cutaneous nodules, HLA DRB1*04 or DRB1*01, and/or AKA are present. The other autoantibodies of diagnostic significance are of little help for predicting joint destruction.

Adolescent↗

PubMed1997

Repetitive cycles of cyclophosphamide, thiotepa, and carboplatin intensification with peripheral-blood progenitor cells and filgrastim in advanced breast cancer patients.

PURPOSE: As an alternative to single-cycle cyclophosphamide, thiotepa, and carboplatin (CTCb) intensification, we evaluated the feasibility of administering one-quarter dose CTCb for four cycles with peripheral-blood progenitor-cell (PBPC) and filgrastim (granulocyte colony-stimulating factor [G-CSF]) in advanced-stage breast cancer patients. PATIENTS AND METHODS: From June 1992 to August 1993, 20 stage IIIB (n = 7) and IV (n = 13) breast cancer patients received 78 cycles of induction with doxorubicin 90 mg/m2 by intravenous (IV) bolus with G-CSF 5 microg/kg/d by subcutaneous injection (SC) repeated every 14 to 21 days for four cycles. PBPC were collected by 2-hour single-blood volume leukapheresis on 2 consecutive days at the time of hematologic recovery from each cycle of doxorubicin. Eighteen patients received 61 cycles of intensification with cyclophosphamide 1,500 mg/m2, thiotepa 125 mg/m2, and carboplatin 200 mg/m2 by IV continuous infusion with G-CSF 10 microg/kg/d SC and PBPC support repeated every 21 to 42 days for four cycles. RESULTS: Twelve of 20 patients (60%) completed all four planned cycles of doxorubicin induction followed by four cycles of one-quarter dose CTCb intensification. Statistically significantly decreases in the yield of mononuclear cells (MNC) (median slope per day, -0.032; P = .03), granulocyte-macrophage colony-forming unit (CFU-GM) (median slope per day, -0.57; P = .0008), and burst-forming unit-erythroid (BFU-E) (median slope per day, -1.18; P = .006) were observed over the course of the eight leukaphereses. Of 18 patients who began CTCb, 12 (67%) completed four cycles. Six patients were removed from study during intensification: two for progressive disease (PD), one refused further treatment, and three for dose-limiting hematologic toxicity. A fourth patient fulfilled the criteria for dose-limiting hematologic toxicity after cycle 4. The toxicity of the multiple cycle CTCb intensification regimen consisted of grade IV leukopenia, grade IV thrombocytopenia, and febrile neutropenia in 100%, 100%, and 26% of cycles, respectively. The median duration of each CTCb cycle was 24 days (range, 18 to 63), and the median duration of an absolute neutrophil count (ANC) < or = 500/microL and platelet count < or = 20,000/microL during each cycle was 6 days (range, 2 to 15) and 4 days (range, 0 to 38), respectively. CONCLUSION: It is feasible to administer repetitive cycles of one-quarter dose CTCb intensification with PBPC and G-CSF. Additional studies are required to determine whether multiple cycles of CTCb intensification might offer a therapeutic advantage over a single high-dose cycle.

Adult↗

PubMed1997

Immunotoxin therapy of small-cell lung cancer: a phase I study of N901-blocked ricin.

PURPOSE: Immunotoxins could improve outcome in small-cell lung cancer (SCLC) by targeting tumor cells that are resistant to chemotherapy and radiation. N901 is a murine monoclonal antibody that binds to the CD56 (neural cell adhesion molecule [NCAM]) antigen found on cells of neuroendocrine origin, including SCLC. N901-bR is an immunoconjugate of N901 antibody with blocked ricin (bR) as the cytotoxic effector moiety. N901-bR has more than 700-fold greater selectivity in vitro for killing the CD56+ SCLC cell line SW-2 than for an antigen-negative lymphoma cell line. Preclinical studies suggested the potential for clinically significant cardiac and neurologic toxicity. We present a phase I study of N901-bR in relapsed SCLC. PATIENTS AND METHODS: Twenty-one patients (18 relapsed, three primary refractory) with SCLC were entered onto this study. Successive cohorts of at least three patients were treated at doses from 5 to 40 microg/kg/d for 7 days. The initial three cohorts received the first day's dose (one seventh of planned dose) as a bolus infusion before they began the continuous infusion on the second day to observe acute toxicity and determine bolus pharmacokinetics. Toxicity assessment included nerve-conduction studies (NCS) and radionuclide assessment of left ventricular ejection fraction (LVEF) before and after N901-bR administration to fully assess potential neurologic and cardiac toxicity. RESULTS: The dose-limiting toxicity (DLT) of N901-bR given by 7-day continuous infusion is capillary leak syndrome, which occurred in two of three patients at the dose of 40 microg/kg (lean body weight [LBW])/d. Detectable serum drug levels equivalent to effective in vitro drug levels were achieved at the 20-, 30-, and 40-microg/kg(LBW)/d dose levels. Specific binding of the immunotoxin to tumor cells in bone marrow, liver, and lung was observed. Cardiac function remained normal in 15 of 16 patients. No patient developed clinically significant neuropathy. However, a trend was noted for amplitude decline in serial NCS of both sensory and motor neurons. One patient with refractory SCLC achieved a partial response. CONCLUSION: N901-bR is an immunotoxin with potential clinical activity in SCLC. N901-bR is well tolerated when given by 7-day continuous infusion at the dose of 30 microg/kg(LBW)/d. Neurologic and cardiac toxicity were acceptable when given to patients with refractory SCLC. A second study to evaluate this agent after induction chemoradiotherapy in both limited- and extensive-stage disease was started following completion of this study.

Adult↗

PubMed1997

Comparing the tensile strength of brackets adhered to laser-etched enamel vs. acid-etched enamel.

This study compared the tensile bond strength of brackets adhered to laser-etched enamel with that of brackets adhered to acid-etched enamel. Forty extracted, intact bovine teeth were treated with either 37 percent phosphoric acid for 15 seconds or neodymium:yttrium-aluminumgarnet laser on black-ink-coated enamel. After thermocycling, tensile stress was applied to the bonded specimens at a 0.1 millimeter/minute orosshead speed. A t-test comparison of means showed a significant difference between the laser-etched and acid-etched teeth, with the acid-etched teeth demonstrating significantly more tensile bond strength at a 95 percent level of significance.

Acid Etching, Dental↗

PubMed1997

High-dose cyclophosphamide, carmustine, and etoposide with autologous transplantation in Hodgkin's disease: a prognostic model for treatment outcomes.

PURPOSE: To identify clinical factors predictive of treatment outcome after high-dose chemotherapy (HDC) for Hodgkin's disease and to develop a prognostic model for progression-free and overall survival. PATIENTS AND METHODS: 102 patients with relapsed or refractory Hodgkin's disease were treated with high-dose cyclophosphamide, carmustine, and etoposide and autologous marrow and/or peripheral blood progenitor cell support. Median follow-up of survivors is 4.1 years (1.8-7.5 years). Factors potentially important for treatment outcome were examined in univariate analysis, and Cox regression with forward selection was performed. A prognostic model was developed. RESULTS: Poorer progression-free and overall survival were associated with nodular sclerosis histology, abnormal performance status, progressive disease at HDC, more than one extranodal site of disease, and shorter time from initial diagnosis to HDC. These factors and the presence of B symptoms at relapse also predicted for decreased overall survival. Progressive disease immediately prior to HDC, more than one extranodal disease site, and abnormal performance status retained significance for both progression-free and overall survival in multivariate analysis. Progression-free and overall survival are 42% (95% confidence interval, CI, 34 to 53) and 65% (95% CI 54 to 73) at three years. A model based on number of risk factors present divides patients into low, intermediate, and high risk groups with three-year actuarial survival of 82%, 56%, and 19% respectively. Treatment outcome for patients treated with HDC at first chemotherapy relapse was not significantly different from that of the group overall (p > 0.3). CONCLUSIONS: Asymptomatic patients with Hodgkin's disease involving at most one extranodal site whose disease is controlled by conventional dose chemotherapy or radiation therapy at the time of HDC have good outcomes after this therapy. Presence of increasing numbers of risk factors are associated with poorer outcomes. Results of HDC compare favorably to those of standard dose salvage therapy. These data can be used to estimate likely outcomes in patients undergoing HDC for Hodgkin's disease, to identify potential candidates for innovative therapies, and to evaluate strategies for the optimal use of HDC in Hodgkin's disease.

Adult↗

PubMed1997

[Cystic adventitial disease: importance of computed tomography in the diagnostic and therapeutic management].

PURPOSE: Popliteal artery entrapment and adventitial cystic disease are the main causes of claudication in young patients. Adventitial cystic disease is a rare vascular pathology mostly affecting the popliteal artery but other localisations have been reported. Diagnosis and therapeutic management of adventitial cystic disease and particularly percutaneous aspiration are presented. MATERIALS AND METHODS: The authors report six cases (four men and two women; mean age: 55) of CAD of the popliteal artery (n = 4) and unusual cases in the femoral artery (n = 1) and in the femoral vein (n = 1) explored by sonography, computed tomography (CT), magnetic resonance imaging (MRI) and angiography. Five patients were initially treated by CT-guided aspiration and one with endoprosthesis. RESULTS: Sonography, CT or MRI are more useful to establish the diagnosis because these techniques can directly visualize the arterial wall. All these patients but one have been treated by percutaneous method with a good functional outcome but surgical intervention was necessary for two of them because of cysts recurrence. CONCLUSION: Our experience suggests that percutaneous CT-guided aspiration is the first treatment option for small cysts but close long-term follow-up is necessary to detect recurrence.

Adult↗

PubMed1997

Anticentromere antibodies in rheumatologic practice are not consistently associated with scleroderma.

Anticentromere antibodies identified by indirect immunofluorescence are a valuable aid to the diagnosis and prognosis of patients with systemic sclerosis since they are associated in 50% to 80% of cases with limited cutaneous systemic sclerosis, a pattern usually associated with a good prognosis. We studied clinical presentations in rheumatology patients with anticentromere antibodies by indirect immunofluoresence and by ELISA and/or Western blot, but without scleroderma or Raynaud's phenomenon. Eight of 34 (23.5%) rheumatology clinic patients with centromere antibodies met these criteria, seven women and one man, with a median symptom duration of six years (range 1-20 years). Four had Sjögren's syndrome, one had isolated xerostomia, one systemic lupus erythematosus, one seronegative symmetric polyarthritis and one primary biliary cirrhosis with arthralgia. The mean anticentromere antibody titer in these eight patients was similar to that in the patients who had at least Raynaud's phenomenon. Given the low incidence of scleroderma, these data illustrate the poor predictive value of anticentromere antibodies for the diagnosis of scleroderma in rheumatology clinic patients.

Adult↗