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D Davignon

Publications and source records attributed to D Davignon.

15 recordsLinked to original sources
PubMed1997

Diagnostic utility of the history and physical examination for peripheral vascular disease among patients with diabetes mellitus.

BACKGROUND: We assessed the value of the medical history and physical examination in the diagnosis of peripheral vascular disease in diabetic subjects. METHODS: We performed a cross-sectional study in 631 diabetic veteran enrollees of a general internal medicine clinic that compared data obtained from a history and clinical evaluation with the presence of severe peripheral vascular disease defined as an ankle-arm index (AAI) < or = 0.5 derived from Doppler blood pressure measurement. RESULTS: We identified 90 limbs with an AAI < or = 0.5. Results presented below apply to the right leg, but do not differ from the left. Diminished or absent foot peripheral pulses (sensitivity 65%, specificity 78%), venous filling time > 20 sec (sensitivity 22%, specificity 93.9%), age > 65 years (sensitivity 83%, specificity 54%), claudication symptoms in < 1 block (sensitivity 50%, specificity 87%), and patient reported history of physician diagnosed peripheral vascular disease (PVD) (sensitivity 80%, specificity 70%) had the largest positive (or smallest negative) likelihood ratios. Capillary refill time > 5 sec or foot characteristics (absent hair, blue/purple color, skin coolness, or atrophy) conveyed little diagnostic information. Individual factors did not change disease probability to a clinically important degree. A stepwise logistic regression model identified four factors significantly (p < 0.05) associated with low AAI: absent or diminished peripheral pulses, patient reported history of PVD, age, and venous filling time. Substitution of < 1 block claudication for PVD history in this model resulted in a small reduction in model accuracy. CONCLUSIONS: Many purportedly useful historical and exam findings need not be elicited in diabetic patients suspected of having severe peripheral vascular disease, since most information related to probability of this disorder may be obtained from patient age, self-reported history of physician diagnosed PVD (or < 1 block claudication), peripheral pulse palpation, and venous filling time.

Aged↗
PubMed1996

Increased mortality associated with diabetic foot ulcer.

The objective of this study was to evaluate the relationship between foot ulceration and short-term mortality in veterans of the American military services with diabetes mellitus. A total of 725 diabetic subjects participated in a prospective study of risk factors for lower extremity complications between 1990 and 1994. Mean follow-up was 691.8 days (+/-SD 339.9, range 28-1436 days). Subjects who died during follow-up (n = 72) had a similar mean duration of diabetes to those who survived (12.6 years vs 11.2), but their mean age was greater (65.9 years vs 63.2, p = 0.026). The relative risk (RR) of death was 2.39 (95% confidence interval (CI) 1.13 to 4.58) in the subjects who developed foot ulcer (n = 88) compared to those who did not. The risk of death for those with foot ulcer was 12.1 per 100 person-years of follow-up compared to 5.1 in those without foot ulcer. Cox regression analysis demonstrated a greater than two-fold increased risk of death in ulcerated subjects after adjustment for age; diabetes type, duration, and treatment; glycosylated hemoglobin level; history of lower extremity amputation; and cumulative pack years smoked. Higher ankle-arm index was significantly related to lower mortality risk, independent of foot ulcer occurrence. We conclude that foot ulcer and lower extremity vascular disease are related to a higher risk of death in diabetic subjects. The reasons for this excess mortality require further investigation.

Age Factors↗
PubMed1990

The gerontological nurse practitioner in the nursing home: 12 years later.

Comparing graduates of a GNP program 12 years ago with those graduating from a recent program revealed that GNPs are now staying in their roles. This is in spite of a number of barriers to practice over the years. GNPs also are continuing to work in nursing homes. At the University of Washington, we believed that training and hiring GNPs was one way to improve the care of patients in nursing homes. Our program was designed to meet that goal. That it has been achieved is evidenced by the low turnover and the GNPs' satisfaction in their roles. States should therefore encourage nursing homes to hire GNPs, as in Washington. As the clinical arm for the director of nursing service, and working together with the physician, the GNP can improve patient care as never before.

Geriatric Nursing↗
PubMed1987

Rapid screening with indirect immunotoxin for monoclonal antibodies against human small cell lung cancer.

For the first time, a screening procedure for antitumor monoclonal antibodies (MOABs) has been developed in which the ability of MOABs to mediate the indirect action of another immunotoxin is the primary criterion for selection of hybridomas for expansion and cloning. Use of the indirect immunotoxin makes it possible to screen MOABs for cytotoxic potential without the necessity of covalently coupling toxin to each individual MOAB. Hybridomas derived from spleens of immunized mice were screened for the synthesis of monoclonal antibodies able to participate in the delivery of a pharmacologically active, indirect immunotoxin conjugate to H69 lung cancer cells. The indirect immunotoxin conjugate was goat anti-mouse immunoglobulin disulfide linked to pokeweed antiviral protein. There was no correlation between the results of the screening with the indirect immunotoxin and an enzyme-linked immunosorbent assay screen for binding of MOAB to tumor cell membranes. An indirect immunotoxin prepared from Fab' fragments of goat anti-mouse immunoglobulin was also effective as an indirect immunotoxin conjugate. Each screening of more than 300 hybridomas was performed in 3 days. The indirect immunotoxin screen detected antitumor MOABs which were not detected by the conventional enzyme-linked immunosorbent assay method. A MOAB selected by the indirect immunotoxin screen was conjugated to pokeweed antiviral protein; the conjugate mediated immunocytotoxicity in a standard direct toxicity assay.

Animals↗
PubMed1986

Inhibition of in vitro lymphocyte function by a soluble AKR leukemic suppressor factor.

A soluble suppressor factor(s) found in the serum of AKR mice bearing lymphocytic leukemia (AKR-LSF) has previously been shown to inhibit PHA-induced spleen cell proliferation. In this study we have further characterized the biological activity of the leukemic mouse serum (LMS) in vitro. The LMS inhibits spleen cell proliferation in an MLC as well as generation of functional CTL. The inhibition of CTL generation was not specific since CTL activity resulting from responder and stimulator combinations of various H-2 haplotypes was inhibited. LMS did not inhibit CTL- or NK-mediated cytolytic activity. These results suggested that LMS inhibits lymphocyte proliferative responses but has no effect on cytolytic function. Furthermore, responder cells which had been inhibited by LMS in a primary MLC, washed, and restimulated were able to express CTL activity indicating that the suppression by LMS is reversible. The suppressive effect of LMS is occurring at an early stage of CTL generation since LMS was inhibitory when added on Day 0 or Day 1 but not on Days 2, 3, or 4 of the MLC. Addition of IL-2 did not remove the inhibition by LMS as measured in a PHA proliferative assay. These results suggested that the suppression is not due to a lack of IL-2 but to an inability of the cells to either bind or utilize IL-2.

Animals↗
PubMed1985

Normal T cell subsets and lymphocyte activity in multiple sclerosis.

Nine patients with either chronic progressive or relapsing/remitting multiple sclerosis were treated with several courses of lymphopheresis. The lymphocytes obtained by this procedure showed a significantly lower percentage of OKT3+ cells than normal controls at the beginning of therapy. This percentage increased to normal levels after five lymphopheresis treatments and then decreased during the last stages of treatment. Patients had normal levels of OKT4+ and OKT8+ cells compared to controls and these percentages showed no statistically significant changes during the course of treatment. The proliferative response of patient's lymphocytes after stimulation with concanavalin A, PHA and alloantigen was not significantly different from normal controls and these responses were unchanged during the lymphopheresis treatment. Natural killer cell activity was also normal in our patients. The results reported in this study do not suggest a basic T cell abnormality in our patients with multiple sclerosis. Furthermore, the lymphopheresis treatments did not induce any significant change in T cell numbers or functional activity in vitro.

Adult↗
PubMed1983

Identification and characterization of a soluble suppressor factor(s) in the serum of AKR mice bearing lymphocytic leukemia.

Leukemia in AKR mice was found to be associated with the presence of a serum factor(s) termed AKR leukemic suppressor factor (AKR-LSF). Suppression was quantitated by measuring the inhibition of PHA-stimulated [3H]thymidine incorporation by normal AKR spleen cells at various dilutions of leukemic mouse serum (LMS). AKR-LSF activity was expressed as units per milliliter, which is the reciprocal of the LMS dilution that inhibited [3H]thymidine uptake by 50% with respect to fetal calf serum control cultures. The amount of activity in the serum directly correlated to the rate of tumor cell growth. Mice receiving 10(7) BW5147 transplanted leukemia cells had 130 +/- 12 units of AKR-LSF activity/ml of serum compared to 40 +/- 8 units/ml for mice with spontaneous leukemia. Normal mouse serum contained 33 +/- 11 units/ml. The leukemic serum exhibited no strain specificity in either phytohemagglutinin or lipopolysaccharide assays, but was found to be twofold more inhibitory against mouse spleen cells than that against rat spleen cells. Human lymphocyte blastogenesis was not inhibited by the leukemic serum. LMS did not inhibit the growth of L929 fibroblasts or murine tumor cells in vitro. Further work is necessary to determine what role the suppressor factor may play in the regulation of antitumor cell immunity.

Animals↗
PubMed1982

The molecular basis for cytolytic T lymphocyte function: analysis with blocking monoclonal antibodies.

During the past decade the mechanism of CTL-mediated killing has been resolved into 3 steps, and its cation requirements, and general nature have been well defined. However, biochemical understanding of the CTL-target interaction has made little progress. Recently, we have developed a monoclonal antibody (MAb) which blocks killing by binding to a previously undescribed molecule on the CTL membrane, a molecule which we therefore have termed lymphocyte function-associated antigen one (LFA-1). LFA-1 and Lyt-2,3 are the only presently identified sites for such blocking; antibodies to over a dozen other molecules expressed on the CTL do not block killing. Present evidence suggests that LFA-1 is crucial in the adhesive interaction of T cells with other cells (e.g., targets, macrophages, perhaps B cells) The continuing search for blocking MAbs provides a systematic way to link specific molecules with CTL function.

Animals↗
PubMed1981

Lymphocyte function-associated antigen 1 (LFA-1): a surface antigen distinct from Lyt-2,3 that participates in T lymphocyte-mediated killing.

Monoclonal antibodies (MAb) have been used to probe the relationship of cytolytic T lymphocyte (CTL) surface molecules to CTL function. Rat MAb to mouse CTL were generated. Twelve MAb so obtained gave preferential binding to T cells as compared to B cells, and three of these recognized previously undescribed surface polypeptides. These Mab and more broadly reactive and previously obtained MAb were tested for their ability to block CTL-mediated killing in the absence of complement. To ensure that any observed blocking was due to binding of MAb to the effector cell rather than the target cell, a xenogeneic mouse CTL anti-rat BN lymphoma target cell system was utilized (MAb and target cells both of rat origin). Of 24 MAb tested here, 21 had little or no effect on CTL function, including those to H-2, Thy-1, Lyt-1, Ly 5, Ly 6, Lgp 100, and at least six other defined antigens. We confirmed inhibition of killing with two MAb to Lyt-2,3. Another MAb, M7/14, gave profound and consistent blockade of CTL function. It was confirmed that M7/14 MAb blocks killing by binding to the mouse CTL and does not bind to the rat lymphoma target cells used for the CTL assay. The findings suggest that the antigen defined by M7/14, termed a lymphocyte function-associated antigen, LFA-1, participates in or is closely associated with the mechanism of CTL-mediated killing. LFA-1 contains two polypeptide chains of 180,000 and 95,000 Mr and is distinct from other described lymphocyte glycoproteins. LFA-1 thus represents both a previously undescribed lymphocyte surface antigen and molecular site for blockade of CTL-mediated killing.

Animals↗
PubMed1981

A novel lymphocyte function-associated antigen (LFA-1): cellular distribution, quantitative expression, and structure.

We have previously described a monoclonal antibody (MAb), M7/14, which blocks a variety of T cell functions, including CTL-mediated killing, the mixed lymphocyte response, and antigen-specific proliferation. The antigen defined by M7/14 has been designated lymphocyte function-associated antigen one (LFA-1). In this report, LFA-1 has been studied as to cell distribution, surface abundance, structure, and in comparison to other CTL surface antigens, LFA-1 is expressed on lymphoid cells of both the T and the B lineages and on a large fraction of bone marrow cells, but not on exudate macrophages or nonlymphoid tissues. T cells express more LFA-1 than B cells, both in the unstimulated and stimulated states. Compared with unstimulated spleen cells, cytolytic T lymphocyte cell preparations (CTLP) and Con A blasts, but not LPS blasts, show increased LFA-1 expression relative to H-2, and for T cell-containing populations, Lyt-2. M7/14 MAb binds to about 1.5 X 10(4) and 7 X 10(4) LFA-1 sites per average spleen cell or CTLP cell, respectively. M7/14 Mab binds to cTLP in quantitites of 2.5-fold and ies 10.4-fold less than H-2 and Thy-1 Mab, respectively; since the latter have little or no effect on CTL function, inhibition of killing by M7/14 MAb is specific for the LFA-1 surface site. M7/14 MAb and a blocking Lyt-2 MAb are bound in similar quantities of CTLP. LFA-1 is a glycoprotein and consists of 2 noncovalently linked polypeptide chains of 180,000 and 95,000 Mr. The same molecular species as on CTL is present on other T cells and on B cells. The molecular structure and cell distribution of LFA-1 clearly distinguishes it from Lyt-2,3, Ly-5, T145, and T11, which were previously suggested to be either associated with the function of and/or present on the surface of CTL.

Animals↗