Low vision aids and the presbyope.

When light rays emerge divergent from a low vision device, a presbyopic patient requires a near addition to focus the image. The magnitude of the divergence and the near addition power used by a presbyope can substantially alter the magnification effects of a device. This study examines the effects of different emerging divergences and near addition powers on the magnification of low vision devices. The emerging divergence of 54 fixed focus stand magnifiers was measured using trial lenses and a telescope. The magnifiers represented a range of powers and manufacturers. The emerging divergence was not predictable. It could not be correlated to magnifier power. Although mathematical formulas exist to calculate the effect of the divergence and near addition on magnification, tables were developed to simplify this determination.     

Activated Raf-1 causes growth arrest in human small cell lung cancer cells.

Small cell lung cancer (SCLC) accounts for 25% of all lung cancers, and is almost uniformly fatal. Unlike other lung cancers, ras mutations have not been reported in SCLC, suggesting that activation of ras-associated signal transduction pathways such as the raf-MEK mitogen-activated protein kinases (MAPK) are associated with biological consequences that are unique from other cancers. The biological effects of raf activation in small cell lung cancer cells was determined by transfecting NCI-H209 or NCI-H510 SCLC cells with a gene encoding a fusion protein consisting of an oncogenic form of human Raf-1 and the hormone binding domain of the estrogen receptor (DeltaRaf-1:ER), which can be activated with estradiol. DeltaRaf-1:ER activation resulted in phosphorylation of MAPK. Activation of this pathway caused a dramatic loss of soft agar cloning ability, suppression of growth capacity, associated with cell accumulation in G1 and G2, and S phase depletion. Raf activation in these SCLC cells was accompanied by a marked induction of the cyclin-dependent kinase (cdk) inhibitor p27(kip1), and a decrease in cdk2 protein kinase activities. Each of these events can be inhibited by pretreatment with the MEK inhibitor PD098059. These data demonstrate that MAPK activation by DeltaRaf-1:ER can activate growth inhibitory pathways leading to cell cycle arrest. These data suggest that raf/MEK/ MAPK pathway activation, rather than inhibition, may be a therapeutic target in SCLC and other neuroendocrine tumors.     

Overcoming the hypoxic barrier to radiation therapy with anaerobic bacteria

The low level of oxygenation within tumors is a major cause of radiation treatment failures. We theorized that anaerobic bacteria that can selectively destroy the hypoxic regions of tumors would enhance the effects of radiation. To test this hypothesis, we used spores of Clostridium novyi-NT to treat transplanted tumors in mice. The bacteria were found to markedly improve the efficacy of radiotherapy in several of the mouse models tested. Enhancement was noted with external beam radiation derived from a Cs-137 source, systemic radioimmunotherapy with an I-131-conjugated monoclonal antibody, and a previously undescribed form of experimental brachytherapy using plaques loaded with I-125 seeds. C. novyi-NT spores added little toxicity to the radiotherapeutic regimens, and the combination resulted in long-term remissions in a significant fraction of animals.     

Long-term human response to uncertain environmental conditions in the Andes

Human interaction with the physical environment has increasingly transformed Earth-system processes. Reciprocally, climate anomalies and other processes of environmental change of natural and anthropogenic origin have been affecting, and often disrupting, societies throughout history. Transient impact events, despite their brevity, can have significant long-term impact on society, particularly if they occur in the context of ongoing, protracted environmental change. Major climate events can affect human activities in critical conjunctures that shape particular trajectories of social development. Here we report variable human responses to major environmental events in the Andes with a particular emphasis on the period from anno Domini 500-1500 on the desert north coast of Perú. We show that preindustrial agrarian societies implemented distinct forms of anticipatory response to environmental change and uncertainty. We conclude that innovations in production strategies and agricultural infrastructures in these indigenous societies reflect differential social response to both transient (El Ni?o-Southern Oscillation events) and protracted (desertification) environmental change.     

Targeting and therapy of human glioma xenografts in vivo using radiolabeled antibodies

Radiolabeled antibodies provide a potential basis for selective radiotherapy of human gliomas. Monoclonal P96.5, a mouse IgG2a immunoglobulin, defines an epitope of a human melanoma cell surface protein and specifically binds the U-251 human glioma as measured by immunoperoxidase histochemistry. 111In-radiolabeled P96.5 specifically targets the U-251 human glioma xenograft and yields 87.0 microCuries (uCi) of tumor activity per gram per 100 uCi injected activity compared to 4.5 uCi following administration of radiolabeled irrelevant monoclonal antibody. Calculations of targeting ratios demonstrate deposited dose to be 11.6 times greater with radiolabeled P96.5 administration compared to irrelevant monoclonal antibody. Tumor dose found in normal organs is less than 20% of the tumor dose, further supporting specific targeting of the human glioma xenograft by this antibody. Monoclonal antibodies QCI054 and ZME018, which define a tumor-associated and a second melanoma-associated antigen, respectively, demonstrate positive immunoperoxidase staining of the tumor, but comparatively decreased targeting. To test the therapeutic potential of 90Y-radiolabeled P96.5, QCI054, and ZME018, tumors and normal sites were implanted with miniature thermoluminescent dosimeters (TLD). Average absorbed doses of 3770 +/- 445 (mean +/- SEM), 2043 +/- 134, and 645 +/- 48 cGy in tumor, 353 +/- 41, 243 +/- 22, and 222 +/- 13 cGy in a contralateral control intramuscular site, 980 +/- 127, 815 +/- 41, and 651 +/- 63 cGy in liver, and 275 +/- 14, 263 +/- 11, and 256 +/- 18 cGy in total body were observed 7 days following administration of 100 uCi 90Y-radiolabeled P96.5, QCI054, and ZME018, respectively. To test the therapeutic potential, tumor-bearing nude mice were given intracardiac injections of either buffer or 90Y-radiolabeled P96.5, QCI054, or ZME018. Striking tumor regression and prolonged survival were measured following administration of 90Y-labeled P96.5. Average maximal decreases in tumor volume were 42.7 +/- 11.9 and 94.2 +/- 3.3 percent 28 and 58 days following 100 and 200 uCi 90Y-radiolabeled P96.5 administration, respectively. The time required to achieve four times the initial tumor volume was 6.1 +/- 0.9 days for buffer; 43 +/- 12 and 63 +/- 10 days for 50 and 100 uCi 90Y-radiolabeled P96.5; 7 +/- 2, 20 +/- 1, and 53 +/- 4 for 50, 100, and 200 uCi 90Y-radiolabeled QCI054; and 9 +/- 1, 13 +/- 1, and 29 +/- 3 days for 50, 100, and 200 uCi 90Y-radiolabeled ZME018, respectively. Average tumor regrowth failed to occur 180 days following administration of 200 uCi 90Y-labeled P96.5.(ABSTRACT TRUNCATED AT 400 WORDS)     

Caregivers for Alzheimer's patients: what we are learning from research

The research literature on adjustment by family members to providing care to victims of Alzheimer's disease is new and expanding rapidly. The purpose of this review is to summarize the categories and methods of that research; to evaluate critically the state of knowledge these studies are producing; and to suggest ways of strengthening future investigations. The review is organized around psychological, social, and health factors as antecedents or correlates of similar categories of outcomes for caregivers. While there are some emerging relationships involving caregiver burden, depression, and psychological well-being, it is difficult to generalize about the determinants or correlates of the consequences of meeting caregiver responsibilities; this difficulty probably results from a failure to deal adequately with key concepts and circumstances of the caregiver. These conceptual and methodological shortcomings are discussed and suggestions for refinement made.     

Inhibition of phagocytosis and interleukin-1 production in pulmonary macrophages from rats with sialodacryoadenitis virus infection

To test whether or not sialodacryoadenitis virus (SDAV) infection in rats affects pulmonary macrophage function, we intranasally inoculated pathogen-free F344 rats with SDAV and collected alveolar and interstitial macrophages 5 d later. We assessed Fc receptor-mediated attachment and phagocytosis by phase-contrast microscopic examination of monolayers of alveolar and interstitial macrophages incubated with zymosan, nonopsonized sheep erythrocytes, or erythrocytes opsonized with rabbit antisheep-erythrocyte IgG. Alveolar macrophages from virus-infected rats had significantly (P less than or equal to .05) lower indices of attachment and phagocytosis of opsonized erythrocytes than control macrophages, but there was no difference in attachment of zymosan particles. Interstitial macrophages were not affected. Alveolar macrophages from SDAV-infected rats produced significantly less interleukin-1 than those from control rats, as assessed by testing supernatants from lipopolysaccharide-stimulated macrophage cultures for induction of mouse thymocytes to take up tritiated thymidine. Effects of SDAV infection on lung macrophages could increase host susceptibility to other pathogens or complicate studies of respiratory tract immunity.     

The ultrasonographic characterization of tendons

Ultrasonography has not been utilized in the diagnosis of musculoskeletal disorders. However, the superficial location of tendons and ligaments lend themselves to evaluation by this modality. The ultrasonographic characteristics of the normal Achilles tendon are described in both the rabbit and man. The characteristic ultrasonographic findings after injury to the Achilles tendon are also determined. This imaging technique provides a sharp definition of the tendon and surrounding structures and easily demonstrates abnormalities. The superficially located quadriceps tendon is also well visualized by ultrasound and representative examples are shown. Ultrasound should be considered as another useful method for evaluation of these superficial musculoskeletal structures.