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Biomedical subjects

W Gordon

Publications and source records attributed to W Gordon.

At least 19 recordsLinked to original sources
PubMed2001

Preparation and application of antibodies to phosphoamino acid sequences.

In this review, we describe methods to generate and characterize sequence-specific phosphoamino acid antibodies. Several of the early contributions regarding the utility of such antibodies are summarized. Three antiphosphopeptide antibodies derived from sequences of the Bcr protein are described. They are anti-Bcr pSer-354, anti-Bcr pTyr-328, and anti-Bcr pTyr-360. These anti-Bcr phosphopeptide antibodies are directed toward phosphorylated sequences encoded by the first exon of the BCR gene, which is the critical portion of the Bcr sequence present in the Bcr-Abl oncoprotein. Using these antibodies, we established/confirmed the in vivo phosphorylation of Ser-354, Tyr-328, and Tyr-360 in Bcr and Bcr-Abl proteins. The cross-reactivity of these antibodies, which is a common problem with antipeptide antibodies, was also investigated and discussed.

Amino Acid Sequence↗
PubMed2001

The reliability and validity of the SF-36 health survey questionnaire for use with individuals with traumatic brain injury.

In order to examine the reliability and validity of the SF-36 for use with individuals with TBI, the SF-36 and three measures of health-related problems in persons with TBI (BDI-II, TIRR Symptom Checklist, Health Problems List) were administered to 271 individuals without a disability, 98 individuals with mild TBI, and 228 individuals with moderate-severe TBI. Internal consistency (reliability) was demonstrated for all SF-36 scales. Significant correlations were found between the SF-36 scales and the other measures, with stronger correlations emerging in the TBI groups. The TBI groups obtained significantly lower SF-36 scores than the comparison group, and the mild TBI group scored lower than the moderate-severe group. For the most part, the differences between the TBI groups disappeared when BDI-II scores were controlled for. These findings suggest that the SF-36 is a reliable and valid measure for use with persons with TBI.

Adolescent↗
PubMed2001

Impact of demographic and medical factors on satisfaction with life after spinal cord injury: a normative study.

OBJECTIVE: The aim of this study was (1) to examine demographic and medical predictors of the Satisfaction With Life Scale (SWLS) among individuals with spinal cord injury (SCI) and (2) to provide a normative table for the SWLS that includes appropriate adjustments for the most important predictors of life satisfaction. STUDY DESIGN: We examined predictors of the SWLS including age, education, sex, race, injury duration, number of rehospitalizations, marital status, employment status, SCI etiology, and level of neurological impairment. PARTICIPANTS: Individuals in the National Spinal Cord Injury Statistical Center database [from 18 SCI model systems (1995-1999)] undergoing follow-up assessment were included for study. OUTCOME MEASURE: Satisfaction With Life Scale. RESULTS: Univariate analyses indicated that marital and employment status, race, sex, education, and injury duration were significant factors associated with scores on the SWLS. In general, individuals who were female, white, married, and currently employed and had a higher education and longer injury duration reported significantly higher scores on the SWLS (P < .01). Effect-size estimates for these factors ranged from 0.16 to 0.41. Regression analyses showed that education, employment status, and injury duration were the strongest unique predictors of satisfaction with life but accounted for only 10% of the variance. CONCLUSION: The SWLS is a global measure of life satisfaction and is relatively unrelated to demographic and medical characteristics. Normative tables are provided for epidemiologic comparison.

Adolescent↗
PubMed2000

Concurrent chemotherapy and pelvic radiation therapy compared with pelvic radiation therapy alone as adjuvant therapy after radical surgery in high-risk early-stage cancer of the cervix.

PURPOSE: To determine whether the addition of cisplatin-based chemotherapy (CT) to pelvic radiation therapy (RT) will improve the survival of early-stage, high-risk patients with cervical carcinoma. PATIENTS AND METHODS: Patients with clinical stage IA(2), IB, and IIA carcinoma of the cervix, initially treated with radical hysterectomy and pelvic lymphadenectomy, and who had positive pelvic lymph nodes and/or positive margins and/or microscopic involvement of the parametrium were eligible for this study. Patients were randomized to receive RT or RT + CT. Patients in each group received 49.3 GY RT in 29 fractions to a standard pelvic field. Chemotherapy consisted of bolus cisplatin 70 mg/m(2) and a 96-hour infusion of fluorouracil 1,000 mg/m(2)/d every 3 weeks for four cycles, with the first and second cycles given concurrent to RT. RESULTS: Between 1991 and 1996, 268 patients were entered onto the study. Two hundred forty-three patients were assessable (127 RT + CT patients and 116 RT patients). Progression-free and overall survival are significantly improved in the patients receiving CT. The hazard ratios for progression-free survival and overall survival in the RT only arm versus the RT + CT arm are 2.01 (P =.003) and 1.96 (P =. 007), respectively. The projected progression-free survivals at 4 years is 63% with RT and 80% with RT + CT. The projected overall survival rate at 4 years is 71% with RT and 81% with RT + CT. Grades 3 and 4 hematologic and gastrointestinal toxicity were more frequent in the RT + CT group. CONCLUSION: The addition of concurrent cisplatin-based CT to RT significantly improves progression-free and overall survival for high-risk, early-stage patients who undergo radical hysterectomy and pelvic lymphadenectomy for carcinoma of the cervix.

Adult↗
PubMed1999

Variant antibody identification by peptide mapping.

During development of CGP56901, a monoclonal antibody (MAb) specific for a unique epitope on human IgE, the protein A-purified IgG from one of the candidate production cell lines, showed an additional minor heavy chain (H-chain) band with a molecular weight slightly lower than that of the principal H-chain band on SDS-PAGE. The N-terminal amino acid sequence of this minor H-chain species indicated that at least the first 30 amino acids were identical to those of the antibody light-chain (L-chain) variable domain. More detailed studies using peptide mapping and amino acid sequencing analysis confirmed a crossover event between the V genes of the antibody. The position is between Arg108 of the L chain and Ala124 of the H chain. This crossover resulted in a variant H chain, which had 16 fewer amino acid residues than the normal CGP56901 H chain. These results show that peptide mapping is a useful "first-line" analytical tool in the characterization of the quality of the monoclonal antibody.

Amino Acid Sequence↗
PubMed1999

Access to the environment and life satisfaction after spinal cord injury.

OBJECTIVE: To determine the potential relation between satisfaction with life after spinal cord injury and access to the environment as measured by selected items from the Craig Handicap Assessment and Reporting Technique (CHART). DESIGN: Prospective, correlational/predictive study using cross-sectional and longitudinal data from 18 Model Spinal Cord Injury Systems of Care. SUBJECTS: Adult persons with traumatic-onset spinal cord injury (n = 650) evaluated at 1 or 2 years postinjury. OUTCOME MEASURE: Satisfaction With Life Scale (SWLS). PREDICTOR VARIABLES: Demographic characteristics, impairment and disability classifications. medical complications, rehabilitation insurance status, occupational status as measured by the CHART Occupation Scale, self-perceived health (from SF-36), and access to the environment as measured by items from the CHART Mobility Scale. RESULTS: Access to the environment was positively and linearly associated with satisfaction with life, demonstrated both positive and negative change over time, and was positively associated with subject's neurologic status. Access to the environment added to the explanatory model to predict life satisfaction even after all other independent measures were accounted for. CONCLUSION: Access to the environment (an "outside the person" factor) is important in predicting satisfaction with life for persons with spinal cord injury. The measure of access to the environment developed here is promising and worthy of further exploration and expansion.

Activities of Daily Living↗
PubMed1999

The relationship of cognitive, personality, and academic measures to anesthesiology resident clinical performance.

UNLABELLED: Cognitive skills (including vigilance), personality factors, and standardized academic test performance may be associated with clinical competence in anesthesiology to varying degrees. Sixty-seven anesthesiology residents in training at one center between 1993 and 1995 were administered the modified Vigil (For Thought, Ltd., Nashua, NH), the Paced Auditory Serial Addition Test, the California Personality Inventory, the State-Trait Anxiety Inventory, and five standardized academic performance tests. The clinical performance of anesthesiology residents was rated on a quarterly basis by a clinical competence committee. A growth curve model indicated that there was significant variability in clinical competence at the start of residency and a statistically significant improvement over time, and that the relative ranking of the residents remained stable over the course of training. Of 46 potential variables, 7 were associated (P < 0.10) with poor clinical performance; these were subjected to a multivariate test (Mantel-Haenszel). Cognitive variables predicting poor clinical performance were difficulty performing a rapid mental arithmetic test requiring divided attention and commission errors during complex visual target detection. Personality variables predicting poor clinical performance were introversion and flexibility. A predictive academic variable was poor anesthesia knowledge as measured by using two different tests during the first month of training. There were varying levels of independence among these variables. IMPLICATIONS: Early academic test performance and certain cognitive and personality tests were associated with the clinical performance of anesthesiology residents. The predictive value of these findings should be confirmed in a prospective, multicenter study.

Anesthesiology↗
PubMed1997

A study of reproductive function in patients with seminoma treated with radiotherapy and orchidectomy: (SWOG-8711). Southwest Oncology Group.

PURPOSE: The results of Southwest Oncology Group Study 8711 (Group 2B) are presented. The objective was to evaluate the natural history of sperm concentration and selected hormonal parameters in patients with testicular cancer treated with orchiectomy and radiotherapy. METHODS AND MATERIALS: Of a total of 207 patients enrolled on SWOG 8711, 53 pure seminoma patients were identified who were treated with orchiectomy and radiotherapy only. Sperm concentration, follicle-stimulating hormone (FSH) levels, and sexual satisfaction scores were the main parameters followed. RESULTS: A fraction of the patients were infertile prior to receiving radiotherapy. Our analysis indicates that incidental radiation dose to the remaining testicle affects time to recovery of fertility, and at an aggregate level, changes in FSH mirror changes in sperm concentration over time. This phenomenon is the same as that described in patients free from testicular cancer. These men evaluated their sexual activity as good after orchidectomy. CONCLUSION: Our data support the use of clamshell-type testicular shields as a means of providing maximum protection to the remaining testicle.

Adult↗
PubMed1997

The effect of intravenous administration of a chimeric anti-IgE antibody on serum IgE levels in atopic subjects: efficacy, safety, and pharmacokinetics.

CGP 51901 is a non-anaphylactogenic mouse/human chimeric anti-human IgE antibody that binds to free IgE and surface IgE of IgE-expressing B cells but not to IgE bound to high affinity IgE receptors (Fc epsilonR1) on mast cells and basophils or low affinity IgE receptors (Fc epsilonR2) on other cells. A phase 1 double-blind, placebo-controlled, single dose study with doses of 3, 10, 30, and 100 mg of CGP 51901 was conducted in 33 pollen-sensitive subjects who had raised levels of serum IgE and received either intravenous CGP 51901 or placebo. The administration of CGP 51901 was well tolerated and resulted in a decrease of serum free IgE levels in a dose-dependent manner, with suppression after 100 mg of CGP 51901 reaching > 96%. Time of recovery to 50% of baseline IgE correlated with the dose of administered antibody and ranged from a mean of 1.3 d for the 3 mg to 39 d for the 100 mg dose. Total IgE, comprised of free and complexed IgE, increased as stored and newly synthesized IgE bound to CGP 51901. Complexed IgE was eliminated at a rate comparable with the terminal half-life of free CGP 51901 (11-13 d at all doses). Only one subject showed a weak antibody response against CGP 51901. We conclude that the use of anti-human IgE antibody is safe and effective in reducing serum IgE levels in atopic individuals and provides a potential therapeutic approach to the treatment of atopic diseases.

Adolescent↗
PubMed1995

Ruptured and unruptured intracranial aneurysms--surgical outcome.

BACKGROUND: The treatment of unruptured, intracranial aneurysms has been the topic of debate. Although recent studies have advocated surgical intervention for unruptured aneurysms, the risk of such treatment in comparison to outcome from ruptured aneurysms has not been established. METHOD: This retrospective study examines the outcome of 134 patients with 179 ruptured and unruptured intracranial, saccular aneurysms treated by a single surgeon. RESULTS: Of the 98 ruptured aneurysms where early surgical intervention was undertaken (less than 48 hours post hemorrhage), 70 had an excellent outcome, 13 were good, four were moderate, two poor and nine patients died postoperatively. Outcome assessment in these cases was correlated to preoperative neurological status. Patients who presented with unruptured aneurysms fell into two categories: symptomatic and asymptomatic. Seven incidental, asymptomatic aneurysms were clipped concurrently to the surgical isolation of the culprit lesion following subarachnoid hemorrhage without influencing outcome, whilst, for varying reasons, eight unruptured aneurysms were not operated upon. Of the remaining 66 surgically treated, unruptured aneurysms, 64 had an excellent postoperative result, one was good (persisting right incomplete third nerve palsy) and one was moderate (left hemiparesis). Thirteen of these aneurysms were symptomatic, whilst 21 were asymptomatic, multiple aneurysms requiring secondary elective repair and 32 were true incidental aneurysms. CONCLUSION: Unruptured aneurysms less than 25 mm in size may be safely, surgically treated relative to the expected natural history and, certainly, with less risk than operative intervention upon ruptured cerebral aneurysms.

Adult↗
PubMed1995

Early complications and long-term survival in severely obese coronary bypass patients.

Our objective was to describe the short-term morbidity of coronary artery bypass operations and the effect of surgery plus aggressive cardiac rehabilitation on the long-term prognosis of severely obese patients with coronary artery disease. We investigated an inception cohort of 28 consecutive severely obese patients with three-vessel coronary disease followed on average for 51 months. The patients' age, preoperative and postoperative weight, risk factors, and cholesterol were measured. We performed coronary artery bypass surgery, then began aggressive cardiac rehabilitation programs. We recorded intraoperative data, perioperative deaths, complications, readmissions, and lengths of stay. Also, New York Heart classifications and use of anti-anginal or cholesterol-lowering medications were noted. All patients were followed up. Despite high morbidity, long-term function and survival of severely obese CABG patients compares favorably with that of average patients. However, aggressive behavior modification fails to alter their postoperative weight or risk profile, placing them at risk for both second CABG procedures and continued obesity-related disease occurrences.

Behavior Therapy↗
PubMed1993

Pharmacokinetics of an HIV-1 gp120-specific chimeric antibody in patients with HIV-1 disease.

The pharmacokinetics of mouse V/human C (gamma 1, kappa) chimeric monoclonal antibody CGP 47 439 specific for the principal neutralizing determinant of human immunodeficiency virus type 1 (HIV-1) was studied in patients with stage IV HIV-1 disease in an open-labeled phase I/IIA trial. Twelve male patients were enrolled and nine completed the study. Patients were divided into three groups according to the extent of CGP 47 439 to bind to gp120 from their viral isolates: undetectable for group 1, modestly reactive for group 2, and strongly reactive for group 3. A first dose of 1, 10, or 25 mg was administered by intravenous infusion to group 1, group 2 and group 3 patients, respectively. The patients then received seven doses of 50, 100, or 200 mg, respectively, every three weeks. CGP 47 439 serum concentrations were determined by an ELISA using monoclonal antibody AB19-4 specific for the idiotope of CGP 47 439. Half an hour after infusion only 25.5-36.1% of the administered antibody was found in the serum, reflecting its rapid distribution in the extravascular space and possibly binding to gp120 antigen in some of the patients. The terminal elimination half-life (T1/2) was 16.2 days in group 1 patients, 9.7 days in group 2 and in group 3 patients 7.5 days and 9.1 days. An antibody response to CGP 47 439 was not a factor in determining elimination rates, because only very low and transient responses were found in three patients. These results suggest that the reactivity of CGP 47 439 with HIV-1 gp120 contributed to its elimination in HIV-1 infected patients.

Adult↗
PubMed1992

Mouse/human chimeric anti-HIV-1 gp120 antibody to the principal neutralizing determinant: tolerability and pharmacokinetics in cynomolgus monkeys, Macaca fascicularis.

In preparing for testing a pharmaceutical grade preparation of chimeric (mouse/human) antibody CGP 47,439 in HIV-1 infected individuals, it was administered to Macaca fascicularis (cynomolgus) monkeys to study tolerability, immunogenicity and pharmacokinetics. Four groups of monkeys, three males and three females per group, received respectively four infusions of 0, 1.43, 4.3, and 14.3 mg of CGP 47,439/kg body weight at one-week intervals. The chimeric antibody induced no fever, was tolerated well throughout the 50-day observation period, elicited no tissue damage and no anti-antibody response. The pharmacokinetic profile was similar at all dose levels with a mean T1/2 alpha of 14.2 h (range 11.8-19.3 h) and a mean T1/2 beta of 172.6 h (range 137.2-220.5h). Following four successive antibody infusions serum concentrations of CGP 47,439 increased without reaching a steady state, and its measured concentrations were comparable to the simulated values. Collectively the study has provided safety and pharmacokinetic data that would allow human studies with this antibody in AIDS patients.

Animals↗
PubMed1992

Heterotopic ossification and other perioperative complications of acetabular fractures.

Thirty-eight operatively treated fractures of the acetabulum were evaluated retrospectively for perioperative complications. Functionally significant heterotopic ossification (Brooker class III or IV) developed in 23% of those patients who did not receive adequate prophylactic irradiation or indomethacin. Irradiation and indomethacin were effective in the prevention of severe heterotopic ossification. The development of severe heterotopic ossification (class III or IV) was associated with increased time from injury to operation. We conclude that prophylaxis against heterotopic ossification is warranted to decrease the incidence of this potentially preventable complication in patients who incur significant time delays prior to surgery. Other significant complications included avascular necrosis (26%), infection (13%), and neural injury (16%). Avascular necrosis developed in one patient who did not have a documented dislocation.

Acetabulum↗
PubMed1991

The management of lung cancer with radiation therapy: where we are now and where we are going.

Cancer of the lung accounts for 14.6% of all new cancers and 35.7% of all cancer deaths. The radiation oncologist is presented with the formidable challenge of trying to deliver high doses of radiation to the malignant lesion while avoiding excessive damage to the surrounding normal tissues. Lung cancer can be classified as either small cell lung cancer or non-small cell lung cancer with respect to its response to therapy. The article reviews the role that radiation therapy plays in the different stages within each classification. Slow progress toward the goal of controlling this disease is being made, and physicians should encourage patients to participate in clinical trials.

Carcinoma, Non-Small-Cell Lung↗
PubMed1990

Monoclonal anti-idiotypic antibody mimicking the principal neutralization site in HIV-1 GP120 induces HIV-1 neutralizing antibodies in rabbits.

A murine mAb BAT123 (Ab1) directing to the principal neutralization site of human T cell leukemia virus (HTLV)-IIIB gp120 (amino acid residue 308-322) was used to generate syngeneic anti-Id mAb (Ab2). Among the Ab2, a mAb AB19-4 was characterized by both serologic and biologic methods to be paratope-specific (Ab2 beta), bearing the internal image of the neutralization site. AB19-4 was found to bind specifically to BAT123 and also to its mouse-human chimeric form in ELISA. The binding of AB19-4 to BAT123 was specifically inhibited by HTLV-IIIB gp120 and the synthetic epitope peptides of HTLV-IIIB and HTLV-IIIMN defined by BAT123. AB19-4 also inhibited the binding of BAT123 to HTLV-IIIB-infected H9 cells in flow cytometric studies. Polyclonal goat and sheep antisera against HTLV-IIIB gp120 reacted specifically with AB19-4, suggesting that AB19-4 may recognize cross-species idiotopes. Rabbits immunized with purified AB19-4 generated anti-anti-Id antibodies (Ab3) that reacted specifically with HTLV-IIIB gp120 and the BAT123-binding epitope peptides of HTLV-IIIB and HTLV-IIIMN. The Ab3 bound to H9 cells infected by HTLV-IIIB or HTLV-IIIMN and inhibited the infection of CEM cells by HTLV-IIIB or HTLV-IIIMN, whereas BAT123 also bound H9 cells infected by HTLV-IIIB or HTLV-IIIMN but neutralized only HTLV-IIIB. Our data suggest that AB19-4 mimics the neutralization site on HIV-1 gp120 defined by BAT123. The induction of immunity to HIV using internal-image Ab2 to HIV-neutralizing antibodies may provide a viable approach for developing effective vaccines for AIDS.

Animals↗