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Biomedical subjects

J Crawford

Publications and source records attributed to J Crawford.

At least 127 records · Page 7Linked to original sources
PubMed1994

Measurement of quality of life in patients with lung cancer in multicenter trials of new therapies. Psychometric assessment of the Lung Cancer Symptom Scale.

BACKGROUND: This study continued the development and psychometric testing of the Lung Cancer Symptom Scale (LCSS), a disease- and site-specific instrument primarily measuring the physical and functional dimensions of quality of life for individuals with lung cancer. The instrument contains two scales, one for patients and a counterpart for health professionals as observers. METHODS: Feasibility, reliability, construct validity, and criterion-related validity were evaluated with 207 patients with non-small cell lung cancer (NSCLC) from six cancer centers. Within an interview with an observer, patients completed part of a battery of instruments by self-report and were interviewed for the remaining measures. Observers also completed measures after the interview. RESULTS: Feasibility, reliability, and validity were well supported for this lung cancer population. Feasibility was demonstrated by patient and staff compliance in completion at all six cancer centers. Internal consistency was good, with coefficient alphas of 0.82 for the patient scale and 0.75 for the observer scale. Construct validity was supported by 1. contrasted groups approach: regression lines (with 95% confidence bands) were obtained between the Karnofsky performance scale (KPS) and each of the two LCSS scales; 2. as a refinement, relationship testing: significant correlations between the LCSS and KPS for each item (except hemoptysis for the patient scale); and 3. multitrait-multimethod approach: good reliability (alphas ranging from 0.75 to 0.93), good convergent validity for the two LCSS scales (r = 0.77), and a good discriminant validity pattern from the Brief Symptom Inventory (BSI). Criterion-related validity with relevant gold standard measures (American Thoracic Society Questionnaire [ATS] and McGill Pain questionnaire, KPS, Profiles of Mood States [POMS], and Sickness Impact Profile [SIP]) was supported with significant correlations (0.40-0.67 for the LCSS patient scale; 0.54-0.65 for the LCSS observer scale). CONCLUSIONS: These psychometric properties demonstrate that the LCSS patient and observer scales are feasible, reliable, and valid quality of life measures that are ready for research and clinical use with lung cancer populations.

Adult↗
PubMed1994

Predicting medical student success in a clinical clerkship by rating students' nonverbal behavior.

OBJECTIVE: To evaluate the relative contribution of affective and cognitive skills to ratings of students' clinical performance by their supervisors. METHODS: Each students' nonverbal behavior was analyzed by examining 33 nonverbal behavioral characteristics in videotape of each of 36 students interviewing a parent or patient three times during a 4-week pediatric clerkship. These ratings were then compared with the student's formal academic evaluation. RESULTS: The 33 nonverbal behavioral characteristics rated for each student were reduced to five composite variables. Three of these correlated significantly with the final grade, providing an affective profile of the highly rated student. Regression analysis of the five composite variables revealed that affective skills accounted for at least 46% of the variance in the students' final grades (multiple R = .68, P = .0015). CONCLUSIONS: Ratings of students' affective characteristics were highly related to clinical evaluations in this pediatric setting. Students who were evaluated highly had a specific affective profile that could be described by analysis of their nonverbal behaviors.

Adult↗
PubMed1994

Inhibition of Plasmodium falciparum lysophospholipase by anti-malarial drugs and sulphydryl reagents.

The activity of lysophospholipase of human erythrocytes increased by about 3 orders of magnitude upon infection with Plasmodium falciparum. The apparent Km for hydrolysis of lysophosphatidylcholine by this enzyme was 50 +/- 7 microM and the apparent Vmax 6.8 +/- 0.6 nmol/h x 10(6) cells. The activity was Ca2+ independent and had a broad pH maximum at pH 8. The enzyme was insensitive to such anti-malarials as mefloquine and arteether and was only weakly inhibited by chloroquine, with a 50% inhibition concentration (IC50) of 70 mM. The anti-malarials quinine and quinacrine were more efficient inhibitors, with IC50s of 2.6 mM and 0.7 mM, respectively. The sulphydryl agents p-hydroxymercuribenzoate (pHMB) and thimerosal were considerably more potent, inhibiting the plasmodial lysophospholipase with IC50s of 18 microM and 10 microM, respectively. When present at 10 microM prior to invasion, both pHMB and thimerosal arrested the growth and reinvasion capacity of P. falciparum in culture. In a synchronized P. falciparum culture the continuous presence of 5 microM thimerosal dramatically decreased total parasitaemia and, within 4 days, totally abolished the capacity of the surviving parasites to reinvade. Thus the plasmodial lysophospholipase may represent a potential new target for anti-malarial chemotherapy.

Animals↗
PubMed1994

Vinorelbine (Navelbine)/carboplatin combination therapy: dose intensification with granulocyte colony-stimulating factor.

Treatment with platinum agents or the new vinca alkaloid vinorelbine (Navelbine; Burroughs Wellcome Co, Research Triangle Park, NC; Pierre Fabre Médicament, Paris, France) results in prolonged survival in patients with advanced non-small cell lung cancer (NSCLC). To determine whether a unique combination of these agents might enhance activity against NSCLC, a combination chemotherapy regimen consisting of intravenous carboplatin, administered on days 1 and 29, and intravenous vinorelbine, given once weekly, was evaluated. Because the dose-limiting toxicity of both agents is myelosuppression, an additional study goal was to assess the ability of granulocyte colony-stimulating factor to alleviate hematologic toxicity and allow on-time, full-dose vinorelbine therapy. To this end, a phase I/II study was begun. Phase I of the study included 22 patients (15 men and seven women) with a median age of 63 years (age range, 39 to 77 years) who had stage IV NSCLC and no prior chemotherapy. Phase I consisted of 28-day cycles in which intravenous carboplatin was administered at an area under the curve of 7 by the Calvert formula, dose range 350 to 450 mg/m2, and intravenous vinorelbine was administered weekly. Granulocyte colony-stimulating factor was administered if dose-limiting neutropenia developed. Four cohorts of patients were studied, ranging from those who received no vinorelbine to those who received drug doses of up to 30 mg/m2. Patients were able to tolerate the highest dose of vinorelbine, but the majority required granulocyte colony-stimulating factor support to do so. No novel toxicities were observed in patients treated with the combination of carboplatin and vinorelbine.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Vinorelbine (Navelbine) in non-small cell lung cancer: future directions.

Randomized clinical trials of vinorelbine (Navelbine; Burroughs Wellcome Co, Research Triangle Park, NC; Pierre Fabre Médicament, Paris, France) as a single agent and in combination with cisplatin have demonstrated antitumor activity in patients with advanced non-small cell lung cancer (NSCLC). Administered as a single agent on a weekly schedule, the vinorelbine therapeutic profile compares favorably with other regimens currently used in palliative treatment of patients with advanced NSCLC. Vinorelbine is also being considered in other treatment settings as well: adjuvant treatment in stage I and II disease, and regimens with curative intent in stage IIIa and IIIb disease. Future directions for vinorelbine in the treatment of NSCLC are likely to be directed toward combination trials with other agents active in NSCLC. Current phase I-II trials, for example, combine vinorelbine with cisplatin, 5-fluorouracil/leucovorin, mitomycin-C, ifosfamide, carboplatin, and paclitaxel (Taxol; Bristol-Myers Squibb Co, Princeton, NJ). Some phase III trials are planned and some are under way. Vinorelbine has been a focus of interest in multimodality trials. A Canadian trial, for example, combined vinorelbine and cisplatin, followed by accelerated radiation. Results from all these trials can be expected to guide the further development of vinorelbine in adjuvant and neoadjuvant settings in NSCLC. Moreover, trials that are documenting the efficacy of vinorelbine in small cell lung cancer are just beginning.

Antineoplastic Agents↗
PubMed1993

Alternative extracellular and cytoplasmic domains of the integrin alpha 7 subunit are differentially expressed during development.

Examination of cDNAs for the laminin-binding alpha 7 integrin subunit identified two different sequences (designated X1 and X2) coding for the variable region between the III and IV homology repeat domains near the putative ligand-binding site. Sequencing of a mouse alpha 7 genomic clone established that the X1 and X2 regions are derived by mutually exclusive alternative mRNA splicing. Reverse transcriptase-polymerase chain reaction analysis of alpha 7 mRNA indicated that the X1 and X2 isoforms were present in equal amounts in mouse skeletal myoblasts and adult heart. However, in adult skeletal muscle, the X2 variant was exclusively expressed. Amino acid sequence homologies in the III/IV segment suggest that alpha 3 and alpha 6 are also alternatively spliced at this site. We identified alternatively spliced exons in a human alpha 6 genomic clone that encode X1- and X2-like segments. Analysis of the alpha 7 cytoplasmic domain indicated that this region was also alternatively spliced and like alpha 3 and alpha 6 could exist as the A or B form. In mouse skeletal and cardiac muscle the B form of alpha 7 was strongly expressed. However, we identified alpha 7A in neonate and adult skeletal muscle but not in cardiac tissue. High levels of alpha 7A were detected in differentiating myotubes, but in proliferating myoblasts only the alpha 7B isoform was present. These results indicate that alternative splicing of alpha 7 mRNA is differentially regulated during development and generates variant integrin chains with structurally and presumably functionally unique ligand-binding and cytoplasmic domains.

Alternative Splicing↗
PubMed1993

Commissural neurons of the electrosensory lateral line lobe of Apteronotus leptorhynchus: morphological and physiological characteristics.

Extracellular injections of horseradish peroxidase were used to label commissural cells connecting the electrosensory lateral line lobes of the weakly electric fish Apteronotus leptorhynchus. Multiple commissural pathways exist; a caudal commissure is made up of ovoid cell axons, and polymorphic cells' axons project via a rostral commissure. Intracellular recording and labeling showed that ovoid cells discharge spontaneously at high rates, fire at preferred phases to the electric organ discharge, and respond to increased receptor afferent input with short latency partially adapting excitation. Ovoid cell axons ramify extensively in the rostro-caudal direction but are otherwise restricted to a single ELL subdivision. Polymorphic cells are also spontaneously active, but their firing is unrelated to the electric organ discharge waveform. They respond to increased receptor afferent activity with reduced firing frequency and response latency is long. Electrical stimulation of the commissural axons alters the behavior of pyramidal cells in the contralateral ELL. Basilar pyramidal cells are hyperpolarized and nonbasilar pyramidal cells are depolarized by this type of stimulation. The physiological results indicate that the ovoid cells participate in common mode rejection mechanisms and also suggest that the ELLs may function in a differential mode in which spatially restricted electrosensory stimuli can evoke heightened responses.

Animals↗
PubMed1993

Carboplatin, etoposide, and radiotherapy, followed by surgery, for the treatment of marginally resectable non-small cell lung cancer.

The present study was undertaken in order to determine the feasibility and efficacy of induction chemotherapy with carboplatin and etoposide, followed by weekly carboplatin and full-course radiotherapy as pre-operative therapy for marginally resectable non-small cell lung cancer (NSCLC). Twenty-eight patients with good Eastern Cooperative Oncology Group (ECOG) performance status ratings and stage IIIA NSCLC received induction chemotherapy with carboplatin (dose computed with the Egorin formula, days 1 and 29) and etoposide (100 mg/m2/day, days 1 through 3 and 29 through 31). This was followed by 100 mg/m2 weekly carboplatin given over 6 weeks, concurrently with 60 Gy radiotherapy. Patients with either responsive or stable disease underwent thoracotomy 4 weeks after the completion of combined-modality therapy. All 28 patients received the first chemotherapy cycle (average carboplatin dose, 407 mg/m2; range, 195 to 586 mg/m2). World Health Organization (WHO) grade 3/4 neutropenia and thrombocytopenia were observed in 53 and 34% of patients, respectively. There were three febrile neutropenic episodes, but no septic deaths. Five patients (18%) required dose reductions prior to the second chemotherapy cycle, but the dose intensity of carboplatin was maintained (average dose, 390 mg/m2; range, 195 to 586 mg/m2). In all, 82% of patients received full-dose radiotherapy, and 73% received at least five of six planned concurrent weekly carboplatin doses. Carboplatin doses were most frequently delayed for thrombocytopenia and/or leukopenia. Carboplatin did not increase the incidence of radiation-induced esophagitis. Only three patients required interruption of radiotherapy, for esophagitis (two patients) and persistent thrombocytopenia (one patient). The response rate to pre-operative therapy was 64%. In this study, we demonstrated the ability to deliver escalated doses of carboplatin with standard-dose etoposide as induction chemotherapy with reasonable myelotoxicity. The combined-modality therapy was well tolerated, and the addition of weekly carboplatin did not result in increased radiation-related toxicity. This neoadjuvant regimen is active in the treatment of locally advanced NSCLC, and compares favorably to other cisplatin-based regimens.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1993

The impact of therapy with filgrastim (recombinant granulocyte colony-stimulating factor) on the health care costs associated with cancer chemotherapy.

The objective of the study was to estimate the net impact on health resource utilisation of using recombinant granulocyte colony-stimulating factor (filgrastim) following myelosuppressive chemotherapy. Cost minimisation of the study medication in a randomised, double-blind, placebo-controlled clinical trial was conducted in teaching institutions and affiliated community hospitals participating in a clinical trial. 68 patients with small cell lung cancer undergoing cyclophosphamide, doxorubicin and etoposide chemotherapy were randomised to blinded placebo or filgrastim study medication at three or 14 clinical trials sites. The patients received daily subcutaneous injections of filgrastim or placebo, initiated 24 h after chemotherapy and continued until the neutrophil count exceeded 10,000 x 10(6)/l after the time of the expected nadir. Differences in total charges, costs and Medicare payments between treatment groups were the main outcomes measured. Compared to placebo patients, filgrastim-treated patients had significantly fewer and less resource-intensive hospitalisations. After accounting for filgrastim purchase and administration, the charge model predicts overall savings from filgrastim use in a clinical setting in which the risk of febrile neutropenia is high for patients not receiving filgrastim. The Medicare and cost models predict only a partial recapture of the cost of filgrastim therapy. The health care resources impact of filgrastim was sensitive to the risk of hospitalisation with febrile neutropenia, and to the perspective chosen for measuring resource utilisation (charges, costs or Medicare payments). The adjunctive use of filgrastim following myelosuppressive chemotherapy leads to partial or complete recapture of the cost of purchasing and administering the product.

Analysis of Variance↗
PubMed1993

A comparative study of monoclonal gammopathies and immunoglobulin levels in Japanese and United States elderly.

OBJECTIVE: To define the prevalence of monoclonal immunoglobulin (Ig) proteins and quantitative serum immunoglobulin levels in elderly Japanese in comparison with elderly Caucasians as possible factors related to the reported lower incidence of multiple myeloma in elderly Japanese than in elderly Caucasians. DESIGN: Survey study SETTING: Community Center in Yokohama, Japan and Retirement Community in the United States. PARTICIPANTS: Convenience sample of community-dwelling elderly subjects (age 63-95) presenting for health screening examinations in each setting. Frozen serum samples were obtained from routine screening from 146 consecutive Japanese subjects and 111 US subjects. INTERVENTION: None MEASUREMENTS: Presence of monoclonal immunoglobulin protein determined by serum protein electrophoresis and immunofixation and quantitative Ig by laser nephelometry. RESULTS: Four (2.7%) of the Japanese cohort had monoclonal gammopathies compared with 11 (10%) of the American cohort. Two of the monoclonal gammopathies were IgG Kappa and two were IgG Lambda. No cases of multiple monoclonal gammopathy were identified in the Japanese group, compared with 25% of the monoclonal gammopathies in the American group. The mean quantitative serum IgG level for the Japanese group was 1,685 +/- 520 mg/dL versus 1,118 +/- 402 mg/dL for the American group; mean quantitative IgA levels were 283 +/- 116 mg/dL versus 226 +/- 116 mg/dL (P < 0.001). Albumin levels were normal in both populations, suggesting that there was not an increase in occult inflammatory disorders in the Japanese population. CONCLUSION: The low prevalence of monoclonal gammopathy in elderly Japanese is consistent with the reported lower frequency of multiple myeloma. The reason for the higher quantitative immunoglobulin levels in this population is unclear. Further cross-cultural investigation is warranted to explore the genetic influences on altered immune regulation with aging.

Age Factors↗
PubMed1993

Combination chemotherapy with or without thoracic radiotherapy in limited-stage small-cell lung cancer: a randomized trial of the Southeastern Cancer Study Group.

PURPOSE: The primary objective of this randomized prospective study was to compare the survival of limited-stage small-cell lung cancer (SCLC) patients treated with chemotherapy alone or chemotherapy plus thoracic radiotherapy (TRT). A secondary objective was to determine the effect of consolidation chemotherapy on survival. PATIENTS AND METHODS: This multiinstitutional phase III study included 386 patients with limited-stage SCLC. All patients received cyclophosphamide 1,000 mg/m2, doxorubicin 40 mg/m2, and vincristine 1 mg/m2 (CAV) every 3 weeks for six cycles. Irradiated patients received 30 Gy in 10 fractions during weeks 1 and 2 of chemotherapy. Fifteen Gy in five fractions was administered during week 7 (total dose, 45 Gy). Following CAV, responding patients were randomized to receive two cycles of consolidation chemotherapy (cisplatin 20 mg/m2/d for 4 days plus etoposide 100 mg/m2/d for 4 days) or observation. RESULTS: Complete (46% and 38%; P = .14) and overall response rates (67% and 64%; P = .58) were not statistically significantly different. Although not significantly different, median (14.4 v 12.8 months) and 2-year survival (33% v 23.5%) rates favored the irradiated patients. Grade 4 hematologic toxicity was greater in irradiated patients (60% and 39%; P < .001). Patients given consolidation chemotherapy experienced superior median (21.1 v 13.2 months; P = .028) and 2-year survival (44% v 26%; P = .028) rates. CONCLUSION: The concurrent use of TRT and CAV chemotherapy as administered in this study failed to improve the survival of limited-stage SCLC patients compared with CAV alone. Life-threatening hematologic toxicities were more frequent with combined-modality therapy. The survival of limited-stage patients treated with CAV (with or without TRT) was improved with two cycles of cisplatin and etoposide consolidation therapy. Whether similar survival results could be achieved with cisplatin and etoposide alone requires additional study.

Adult↗
PubMed1993

Phase II study of intravenous idarubicin in unfavorable non-Hodgkin's lymphoma.

Idarubicin, a new analogue of daunorubicin, was administered intravenously at a dose of 15 mg/m2 to 31 patients with previously treated patients with unfavorable non-Hodgkin's lymphoma. Clinical characteristics included median age 69 years, performance status 1, and prior chemotherapeutic regimens 1. Twenty of the patients were relapsing after prior therapy and 11 were refractory; 29 had received prior anthracycline or anthracenedione. Responses were observed in 43% of patient (3 CR and 10 PR) with a median duration of 10+ months (2-29+ months). Idarubicin was well tolerated with non-hematologic toxicities (nausea/vomiting, mucositis, and anorexia) seen in < 50% of patients. Median hematologic values during the first cycle for this dosage included WBC 1300/mm3, platelets 129,000/mm3, and hemoglobin 10.9 mg/dl. With dose escalation, hematologic toxicity was dose-limiting. Symptomatic cardiac toxicity was observed in one patient who had received maximum dose doxorubicin and radiotherapy. Median values for the cardiac ejection fraction during the full course of therapy for the entire group of patients were 0.62 (initial) and 0.60 (final). Idarubicin in intravenous form is an active drug in previously treated patients with unfavorable non-Hodgkin's lymphoma. Further studies employing idarubicin in non-Hodgkin's lymphoma should be considered. Cardiac function should be followed in trials utilizing anthracycline-type chemotherapeutic agents.

Adult↗
PubMed1993

Job satisfaction in the medical imaging profession: alleviating the shortage of personnel.

The dramatic growth of the diagnostic imaging field has not been accompanied by a similar increase in trained personnel. As a result, a personnel shortage exists in nearly every area of diagnostic medical imaging. A study was conducted to examine job satisfaction among imaging personnel to determine what issues need to be addressed among current employees so that the field of diagnostic imaging may be made more attractive to potential imaging personnel. A total of 71 participants from four hospitals in a mid-size city in the southeastern United States completed a 29-question survey. Demographic characteristics and regression models were then used in statistical analysis. The models examined length of employment, work performance, salary, career advancement, and work environment. Significant factors found to relate to job satisfaction were: relationship with supervisor, opportunity for career advancement, job security, adequate staffing, and job stress. Prioritizing these concerns over other nonsignificant findings should promote job satisfaction and in turn alleviate the current shortage of diagnostic imaging personnel.

Demography↗
PubMed1993

Sustaining safe sex: a longitudinal study of a sample of homosexual men.

OBJECTIVE: TO assess the maintenance of safe sexual practice. (We use the term 'safe' sex throughout the paper, since 'safe' is the term adopted by the Australian National Committee on AIDS). DESIGN: Maintenance was assessed by comparing sexual behaviour with both regular and casual partners reported in a 1986/1987 survey (time 1) with behaviour reported in a second survey in 1991 (time 2). METHOD: The 145 homosexually active participants were a non-clinical sample recruited in 1986/1987 by advertisement and followed-up in 1991. A structured questionnaire was administered at both times. Items included questions about the nature of the men's sexual relationships and their sexual practices. RESULTS: Our findings indicate that the majority of men had sustained safe sex practices. HIV prevention strategies adopted included condom use, avoidance of anal intercourse and negotiated safety (i.e., the negotiated practice of unprotected anal intercourse within regular partnerships of concordant serostatus). CONCLUSIONS: Negotiated safety is not the same as relapse.

AIDS Serodiagnosis↗
PubMed1992

Effect of diacylglycerols on the activity of cobra venom, bee venom, and pig pancreatic phospholipases A2.

The effects of a series of diacylglycerols (DAGs) with varying acyl chain lengths and degree of unsaturation on the activity of cobra venom, bee venom, and pig pancreatic phospholipases A2 (PL-A2S) were studied using two lipid substrates: dipalmitoylphosphatidylcholine (DPPC) or bovine liver phosphatidylcholine (BL-PC). The activities of the phospholipases critically depended on the chain length and degree of unsaturation of the added DAGs and on the chemical composition of the substrate. The effects of DAGs on cobra or bee venom PL-A2S were similar, but significantly different from the pig pancreatic PL-A2. The data, taken together with our previous NMR studies on physicochemical effects of these DAGs on lipid bilayer structure [De Boeck, H., & Zidovetzki, R. (1989) Biochemistry 28, 7439; (1992) Biochemistry 31, 623], allowed detailed correlation of the type of a bilayer perturbation induced by DAG with the activation or inhibition of the phospholipase on the same system. In general, the activation of the phospholipases correlated with the DAG-induced defects of the lipid bilayer structure. The results, however, argue against general designation of DAGs as "activators" or "inhibitors" of PL-A2S. Thus, for example, diolein activated phospholipases with the BL-PC lipid substrate, but inhibited them with the DPPC substrate. Dihexanoylglycerol and dioctanoylglycerol inhibited pig pancreatic PL-A2 with both lipid substrates and inhibited cobra or been venom PL-A2 with the DPPC substrate, but activated the latter two enzymes with the BL-PC substrate. Longer-chain DAGs (C greater than 12), which induce lateral phase separation of the bilayers into the regions of different fluidities, activated all PL-A2S with both lipid substrates.(ABSTRACT TRUNCATED AT 250 WORDS)

1,2-Dipalmitoylphosphatidylcholine↗
PubMed1992

Phase II study of intravenous idarubicin in unfavorable non-Hodgkin's lymphoma.

Idarubicin, a new analogue of daunorubicin, was administered i.v. at a dose of 15 mg/m2 to 31 previously treated patients with unfavorable non-Hodgkin's lymphoma. Clinical characteristics included median age, 69 years; performance status, 1; and prior chemotherapeutic regimens, 1. Twenty of the patients were relapsing after prior therapy and 11 were refractory; 29 had received prior anthracycline or anthracenedione. Responses were observed in 43% of patient (3 complete remission and 10 partial remission) with a median duration of 10+ months (2-29+ months). Idarubicin was well tolerated with nonhematological toxicities (nausea/vomiting, mucositis, and anorexia) seen in less than 50% of patients. Median hematological values during the first cycle for this dosage included WBC, 1,300/mm3; platelets, 129,000/mm3; and hemoglobin, 10.9 mg/dl. With dose escalation, hematological toxicity was dose limiting. Symptomatic cardiac toxicity was observed in one patient who had received maximum dose doxorubicin and radiotherapy. Median values for the cardiac ejection fraction during the full course of therapy for the entire group of patients were 0.62 (initial) and 0.60 (final). Idarubicin in i.v. form is an active drug in previously treated patients with unfavorable non-Hodgkin's lymphoma.

Adult↗