Accumulation of PDGF B and cell-binding forms of PDGF A in the extracellular matrix.

PDGF is a powerful mitogen initially identified within platelets, but also shown to be produced by a wide variety of cell types. PDGF is encoded on two separate genes. These give rise to three polypeptides, PDGF B and two forms of PDGF A (SA and LA), resulting from alternative splicing of the PDGF A gene primary transcript. We report that in CHO cells transfected with PDGF gene constructs and producing moderate levels of PDGF homodimers, much of the PDGF LA and B produced, but little if any SA, is found in the matrix laid down beneath the cells. Immunoreactive PDGF in cells, and in matrix below expressing cells, was visualized by laser confocal microscopy. Western blotting of protein in matrix extracts, cell extracts, and secreted into the growth medium was used to demonstrate that the range of PDGF A polypeptides seen in the matrix was overlapping with those reported previously to be cell associated in cell types such as NIH3T3 and COS 7. This suggests that attachment to matrix or cell surface may be alternative fates for these polypeptides, with fate dependent on the characteristics of the producing cells. Immunoreactive PDGF A and B could be partially released by incubation of matrix material with heparin but not with other glycosaminoglycans. Digestion of matrix with chondroitin ABC lyase but not heparitinase or collagenase displaced some PDGF from its attachment sites. The results indicate attachment of PDGF to matrix proteoglycans, at least partly through the glycosaminoglycan moieties, and perhaps to additional components. The significance of matrix deposition for PDGF action is discussed.

Identifying highly effective psychotherapists in a managed care environment.

OBJECTIVE: To investigate the variability and stability of psychotherapists' effectiveness and the implications of this differential effectiveness for quality improvement in a managed care environment. STUDY DESIGN: Subset archival outcome data for patients receiving behavioral health treatment were divided into 2 time periods to cross-validate the treating therapists' effectiveness. After categorizing the therapists as "highly effective" and "others" during the baseline period, the stability of their individual effectiveness was cross-validated in the remaining time period. METHODS: Outcomes for 10 812 patients (76.0% adults, 24.0% children and adolescents) treated by 281 therapists were included. Patients initiated treatment between January 1999 and June 2004. Mean residual change scores obtained by multiple regression were used to adjust for differences in case mix among therapists. Raw change scores as well as mean residualized change scores were compared between the 71 psychotherapists identified as highly effective (25%) and those identified as other (remaining 75%). RESULTS: During the cross-validation period, mean differences in residualized change score between highly effective therapists and others were statistically significant (difference = 2.8; P < .001), which corresponded to an average of 53.3% more change in raw change scores with the highly effective therapists. Results could not be explained by case mix differences in diagnosis, age, sex, intake scores, prior outpatient treatment history, length of treatment, or therapist training/experience. CONCLUSION: Behavioral health outcomes for a large system of care could be significantly improved by measuring clinical outcomes and referring patients to therapists with superior outcomes.

In vivo protective effects of tetrapeptide AcSDKP, with or without granulocyte colony-stimulation factor, on murine progenitor cells after sublethal irradiation.

Acetyl-N-Ser-Asp-Lys-Pro (AcSDKP) demonstrated hemato-protective activity in mice after sublethal irradiation (7 GY). Bone marrow interleukin-3 (IL-3)-responsive colony-forming cells (CFC and high proliferative potential colony-forming cells (HPP-CFC) were significantly (p < 0.05) increased by day 10 after irradiation in mice receiving a continuous infusion of 1000 ng/day of AcSDKP compared to irradiated control mice. The maximum protective effect for bone marrow progenitors was achieved when AcSDKP was administered for 3 days beginning 24 hours before irradiation. Other dosages and schedules in relationship to irradiation were less active. Further, when granulocyte colony-stimulating factor (G-CSF) was administered for 10 days beginning 24 hours before irradiation. Other dosages and schedules in relationship to irradiation were less active. Further, when granulocyte colony-stimulating factor (G-CSF) was administered for 10 days after AcSDKP infusion in irradiated mice, significantly increased numbers of IL-3 responsive CSF-only control mice. In addition, platelets were significantly (p < 0.05) increased in mice receiving AcSDKP and G-CSF on days 18 and 21 after irradiation compared with mice receiving G-CSF alone. We conclude that ACSDKP has a radioprotective effect in vivo for progenitor cells, and that time of initiation and duration of AcSDKP administration relative to irradiation are crucial for these effects. Further, AcSDKP has a significant additive protective effect not only for progenitor cells but also for platelets when given in combination with G-CSF. We suggest that these in vivo observations provide a basis on which to design optimal clinical hypothesis and protocols.

Technology transfer in digital mammography. Report of the Joint National Cancer Institute-National Aeronautics and Space Administration workshop of May 19-20, 1993.

Digital mammography is one of the most promising novel technologies for further improvement of early detection of breast cancer, offering important potential advantages: 1) improved image quality; 2) digital image processing for improved lesion contrast; 3) computer-aided diagnosis for enhanced radiologic interpretation; and 4) teleradiology for facilitated radiologic consultation. The Diagnostic Imaging Research Branch of the National Cancer Institute (NCI) recently funded an international, multidisciplinary, multi-institutional Digital Mammography Development Group for collaborations between NCI, the academic community, and industry to facilitate the integrated development and implementation of digital mammographic systems. Currently, however, digital mammography faces a number of fundamental technological roadblocks: 1) cost-effective digital detectors and displays for imaging systems; 2) the need for novel algorithms for image processing and computer-aided diagnosis; and 3) high performance, low cost digital networks to provide an "information superhighway" for teleradiology. To solve some of these technological problems, the Diagnostic Imaging Research Branch of NCI joined efforts with the Technology Transfer Division of the National Aeronautics and Space Administration to pursue a federal technology transfer program in digital mammography. The authors discuss the findings and recommendations of the workshop entitled "Technology Transfer in Digital Mammography," which was organized and held jointly by the NCI and the National Aeronautics and Space Administration in May, 1993. Numerous innovative technologies of varying degree of promise for digital mammography were presented at the conference. In this article, specific technologies presented at the workshop by the federal and federally-supported laboratories are described, and critiques of these technologies by the leaders of the medical imaging community are presented.

Spatial association learning by rufous hummingbirds (Selasphorus rufus): effects of relative spacing among stimuli.

Gestalt theory predicts that when cues are spatially separated from response locations, associative learning is faster when distance between cue-response location pairs is increased. This prediction was tested with 20 rufous hummingbirds (Selasphorus rufus), which learned to select rewarding feeders signaled by a spatially separated light cue in 4 treatments in which distance between cues and feeders and between cue-feeder pairs was varied. As has been shown for other animals, the hummingbirds learned more slowly when the distance between cues and feeders was increased, and as predicted by Gestalt theory, they learned faster at a given distance when distance between cue-feeder pairs was increased. This result suggests that spatial association is influenced by the proximity of other stimuli in the visual field.

Hypopharyngeal cancer patient care evaluation.

A survey was conducted to identify demographics and standards of care for treatment of hypopharyngeal squamous cell carcinoma in the United States. Data were accrued from voluntary submission of cancer registry and medical chart information from 769 hospitals representing 2939 cases diagnosed from 1980 to 1985 and 1990 to 1992. Clinical findings, diagnostic procedures employed, treatment practices, and outcome are presented. Overall, 5-year disease-specific survival was 33.4%, which segregated to 63.1% (stage I), 57.5% (stage II), 41.8% (stage III), and 22% (stage IV). Survival was best for patients treated with surgery only (50.4%), similar with combined surgery and irradiation (48%), and worse with irradiation only (25.8%). This analysis provides a standard to which current treatment practice and future clinical trials may be compared.

Patterns of care for cancer of the larynx in the United States.

OBJECTIVE: To assess case-mix characteristics, treatment patterns, and outcomes for laryngeal cancer using the largest series of patients to date. DESIGN: Analyses performed on retrospectively collected survey data submitted by hospitals for diagnostic periods 1980 through 1985 and 1990 through 1992 (with a 9-year follow-up for the long-term group). SETTING: Broad spectrum of US hospitals (N = 769). PATIENTS: Consecutively accrued series of patients with laryngeal cancer (N = 16,936), with only squamous cell carcinomas (N = 16,213) analyzed. INTERVENTIONS: Surgery, radiation therapy, and chemotherapy. MAIN OUTCOME MEASURES: Descriptive analyses of case-mix, diagnostic, and treatment characteristics plus recurrence and 5-year, disease-specific survival outcomes. RESULTS: There was a slight increase across these years in stage IV disease and in radiation therapy (with or without surgery and/or chemotherapy). Overall diversity of management of this disease (by site and stage) was apparent. Five-year survival rates indicated a large difference between modified groupings of the T and N classifications, separating stages III and IV cases into localized disease (87.5% for T1-T2; 76.0% for T3-T4 cases) and regional metastasis (46.2%). CONCLUSIONS: Regardless of improvements in entering data in hospital records (most commendably, staging), more rigorous standards are needed. Also, the small increase in advanced-stage patients indicates that efforts toward early detection have not been successful. The rise in radiation therapy perhaps reflected an increased use of nonsurgical treatment for early-stage patients and organ-sparing radiochemotherapy protocols for advanced-stage patients. Regrouping stages III and IV cases into localized disease vs regional metastasis appears to predict survival better. Ongoing refinements of the American Joint Committee on Cancer staging scheme will hopefully improve this cancer's classification.

Pushing the quality envelope: a new outcomes management system.

This article is based on the authors' experience in designing and implementing outcomes management systems for large managed care organizations. Topics addressed include design of instruments, use of cost-effective technology, development of computerized decision-support tools, and methods for case-mix adjustment. The case-mix-adjustment models are based on a data repository of several thousand treatment cases with multiple measurement points across the course of treatment. Data from controlled and field studies are described. These data suggest that the outcomes management methods outlined in this article can result in significantly improved clinical outcomes and a more rational allocation of behavioral health care resources.

Improving suicide risk assessment in a managed-care environment.

This article describes the quality improvement intervention of a managed behavioral healthcare company to improve the quality of suicide risk assessments by its panel of providers. At-risk cases are identified by the patient's self-reported high frequency of suicidal ideation on a standardized outcome measure. Clinicians also assess severity of suicidal ideation based on clinical interviews. The clinician's assessment is identified as probably erroneous if the patient report indicates a high frequency of suicidal ideation and the clinicians assessment of suicidal ideation is none. The article describes the methods used to encourage clinicians to utilize information from the patient self-report measure as part of the clinical assessment. Probable suicidal ideation assessment errors were subsequently reduced by 29% over a 1-year period of administration.

Permanganate oxidation of sorbed polycyclic aromatic hydrocarbons.

The polycyclic aromatic hydrocarbons (PAH) that contaminate soils at many industrial and government sites are resistant to natural biotic and abiotic degradation processes. The recalcitrant nature of these compounds may require aggressive chemical treatment to effectively remediate these sites. This study was conducted to assess the viability of permanganate oxidative treatment as a method to reduce PAH concentration in contaminated soils. Study results demonstrated a reduction in soil sorbed concentration for a mixture of six PAHs that included anthracene, benzo(a)pyrene, chrysene, fluoranthene, phenanthrene, and pyrene by potassium permanganate (KMnO4) oxidative treatment. The greatest reduction in soil concentration was observed for benzo(a)pyrene, pyrene, phenanthrene, and anthracene at 72.1, 64.2, 56.2, and 53.8%, respectively, in 30 min at a KMnO4 concentration of 160 mM. Minimal reductions in fluoranthene and chrysene concentration were observed at 13.4 and 7.8%, respectively, under the same conditions. A relative chemical reactivity order of benzo(a)pyrene>pyrene>phenanthrene>anthracene>fluoranthene>chrysene towards permanganate ion was observed. Aromatic sextet theory was applied to the degradation results to explain the highly variable and compound-specific chemical reactivity order.

Expert systems restructure managed care practice: implementation and ethics.

The development of computerized decision support technologies is having a profound impact on the management of patient care. This article describes different types of clinical decision support software, examines appropriate usage and current examples of implementation, and reviews a range of ethical considerations. The authors are in the midst of implementing a computerized decision support system for care management in their managed care organization.