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Biomedical subjects

D A Clark

Publications and source records attributed to D A Clark.

At least 181 records · Page 10Linked to original sources
PubMed1994

"Sensing" patient needs: exploring concepts of nursing insight and receptivity used in nursing assessment.

Nursing assessment utilizes skills that enable the nurse to "sense" the patient's needs and the patient's condition, and that provide a humanistic dimension to the provision of nursing care. The explanatory concepts describing these processes include intuition, emotional empathy, inference, knowing, counter transference, compathy and embodiment. In this paper these concepts are defined, and the more commonly used concepts (i.e., intuition, empathy, and inference) are compared. The underlying assumptions and characteristics are identified and the antecedents or prerequisites, mechanisms, and outcomes of each concept are explored. While some overlap and blurring of boundaries are evident, these concepts are diverse and were developed to apply to different contexts and non-nursing situations. When used alone, none is comprehensive enough to account for nurses' ability to sense patient needs. We conclude that, given the unique aspects of nursing, we must consider using innovative methods to examine this phenomenon (e.g., the use of ethology to examine intuitively perceived changes in the patient's condition), to increase efforts to explore the newer concepts (i.e., embodiment, compathy and "knowing"), and to develop new concepts or models that better represent this complex phenomenon that better fits nursing contexts and situations.

Cognition↗
PubMed1994

The West Point Study: 40 years of follow-up.

Completion of cardiovascular evaluations of 387 members marked the end of 40 years of follow-up in the West Point Study. Coronary artery disease (CAD) caused 4 cases of sudden death, 14 cases of myocardial infarction (MI), 13 cases of angina, and 17 cases of silent CAD. Using risk factors (serum cholesterol, estimated HDL-cholesterol, systolic blood pressure, and smoking status) measured before age 28, we derived a multivariate regression formula for predicting which members of the study, had they been pilots, would have been grounded for CAD before age 55. This derivation used data from only those subjects with CAD or with no evidence of CAD. We then used the formula to compute a risk-related score for each member of the study. In the tertile group with the highest risk-related scores, 17% manifested CAD by age 55 and the first event occurred at age 39. In the tertile group of lowest scores, 2% experienced CAD by age 55 and the first event occurred at age 51. We conclude that it is possible to select pilot candidates with the lowest risk for CAD.

Adult↗
PubMed1993

Nitric oxide: the Jekyll and Hyde of gut inflammation.

We studied the effects of seven day treatment with the nitric oxide synthase (NOS) inhibitor NG-nitro-L-arginine (L-NAME), administered in the drinking water (100 micrograms/ml ad lib) of female guinea pigs. The effects of NOS inhibition were evaluated in naive animals and in guinea pigs with ileitis induced by intraluminal trinitrobenzenesulfonic acid (TNBS). After 7 days, animals were anesthetized, a sterile saline lavage injected into an ileal loop and removed after 30 min for analysis. In naive guinea pigs, L-NAME caused a marked increase in ileal myeloperoxidase activity and conversion of the mucosa from an absorptive to a secretory state. TNBS-treated guinea pigs has a similar, marked increase in granulocyte infiltration and a mucosal secretory response. However, in contrast to naive animals, L-NAME treatment was anti-inflammatory, reverting all responses to the basal state. We conclude that intestinal nitric oxide serves an anti-inflammatory role under basal conditions, whereas in the TNBS model of chronic ileitis, nitric oxide is a critical mediator of gut injury.

Administration, Oral↗
PubMed1993

Obsessive intrusive thoughts in nonclinical subjects. Part I. Content and relation with depressive, anxious and obsessional symptoms.

The present study reports on the development and preliminary validation of a 52 item self-report instrument designed to assess intrusive thoughts, images and impulses that are similar to the aggressive, sexual and disease-related thinking characteristic of clinical obsessions. Two hundred and ninety-three students completed the Obsessive Intrusions Inventory (OII) as well as standard self-report measures of negative cognitions and obsessive, anxious and depressive symptoms. Regression analysis revealed that intrusive thinking was a significant and unique predictor of obsessional but not anxious or depressive symptoms. Furthermore, intrusive thinking showed a moderate correlation with anxious but not depressive cognitions. The results indicate that the intrusive thoughts assessed by the OII are distinct from other forms of negative thinking and may, in fact, constitute an analogue form of clinical obsessions in nonclinical populations.

Adolescent↗
PubMed1993

Effect of prostaglandin synthesis inhibitors on spontaneous and endotoxin-induced abortion in mice.

The putative role of prostaglandin E2 (PGE2) in suppressing rejection of the 'fetal allograft' (resorption) in C3H/HeJ and CBA/J allopregnant mice was tested by administration of the prostaglandin synthesis inhibitors indomethacin (INDO) and acetylsalicylic acid (ASA). When the resorption rate was low, INDO fed at a dose of 15 micrograms/ml in drinking water after implantation had a slight augmenting effect when the endogenous resorption rate was < 30%, but had no effect when the endogenous rate was higher or when bacterial lipopolysaccharide (LPS) was given. ASA fed at 50 micrograms/ml had no augmenting effect and did not increase sensitivity to the abortogen LPS in either CBA/J (LPS sensitive) or C3H/HeJ (LPS resistant) mice. Both INDO and ASA fed to CBA/J mice significantly reduced endogenous PGE2 extractable from the uteri of hormonally pseudopregnant mice after deciduoma induction. Feeding INDO at doses up to 30 micrograms/ml from day 2.5 of pregnancy impaired but failed to completely block implantation in CBA/J mice, and with daily administration, some of the mice became sick: all of the implants in sick mice resorbed. INDO at doses of 150-200 micrograms per day known to inhibit implantation in vivo by sufficiently blocking PGE2 synthesis, was injected on one or more days beginning after the time of implantation. This failed to cause abortion in CBA/J mice and although some mice became ill, provided this happened after day 8.5 of pregnancy when sensitivity to the abortogenic effects of injected LPS decreased substantially in these mice, all implants in the sick mice were 'healthy' (i.e. non-resorbing). We were unable to increase the rate of resorption in syngeneically pregnant CD1 mice above 13% with 15 ml INDO in drinking water. Our data do not support the view that PGE2 represents an important intrauterine suppressor molecular blocking the processes mediating embryo death at the time of abortion. Spontaneous abortion in DBA/2-mated CBA/J mice appears to be determined by the level of bacterial LPS (endotoxin) and treatment with antibiotics or intralipid (which enhances endotoxin clearance), reduces the abortion rate. A sufficient dose of INDO may cause abortion, but the data taken together suggest this may be due to effects on the gut whereby permeability to bacterial LPS is increased.

Abortion, Spontaneous↗
PubMed1993

Dyspermia in men with localized Hodgkin's disease. A potentially reversible, immune-mediated disorder.

Localized Hodgkin's disease (HD) is curable in the great majority of patients. However, common programs of chemotherapy for this disease render most men permanently azoospermic. In studies of seminal cryopreservation prior to treatment, it has been recognized that many men with HD are dyspermic at diagnosis. It is hypothesized that this abnormality reflects a change in the cellular regulation of spermatogenesis; specifically an alteration in the balance between distinct sub-populations of lymphocytes which normally either inhibit or stimulate the production of sperm. This change in regulation within the testes is believed to be part of a systemic perturbation which is unrelated to the extent of HD but is potentially reversible with effective treatment of the primary disease. Recognizing the distinction between sperm analyses and fertility status, it is proposed that radiotherapy of localized HD, delivered in a manner that is not toxic to the male gonad, will restore useful spermatogenesis in patients who are dyspermic (and probably subfertile) before treatment is initiated.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1993

Effects of decidual cell supernatants and lymphokines on murine trophoblast growth in vitro.

Blastocysts were flushed from CD1 mice and were cultured in plastic or laminin-coated plates as an in vitro model of implantation. The purified cytokines epidermal growth factor (EGF) and platelet-derived growth factor (PDGF) markedly stimulated 3H-thymidine incorporation; but recombinant murine granulocyte-macrophage colony-stimulating factor (GM-CSF), which might be produced by alloantigen-stimulated T cells at the feto-maternal interface, had no growth-stimulating effect. Indeed, higher nonphysiological concentrations of GM-CSF manifested a toxic inhibition. Surprisingly, a purified nonrecombinant murine GM-CSF preparation induced proliferation of both blastocyst and ectoplacental cone trophoblast whereas recombinant murine (and human) GM-CSF had no effect, indicating that the growth stimulation may have been due to a contaminant. Decidual supernatants prepared on Days 5.5-6.5 of pregnancy from mice with high abortion rates (DBA/2-mated CBA/J) had no toxic or stimulating effect on blastocyst trophoblast outgrowth compared to similarly prepared supernatants from low-abortion-rate DBA/2-mated C3H/HeJ mice. These data suggest that it is not GM-CSF that is crucial for the trophoblast proliferation that determines the success of pregnancy.

Animals↗
PubMed1993

Stress-triggered abortion in mice prevented by alloimmunization.

PROBLEM: To determine if immunotherapy can prevent abortion triggered by mechanisms that in humans may be treatable by psychotherapy. METHOD: The effects of alloimmunization against paternal strain antigens were tested in pregnant mice subjected to stress. RESULTS: Restraint stress boosted the resorption rate assessed on day 13.5 of pregnancy in DBA/2-mated C3H/HeJ mice with an optimal effect on day 4.5 of pregnancy, and premating alloimmunization greatly reduced the effect. By contrast, CBA/J and A/J mice proved resistant to abortion boosting by restraint stress. A/J mice mated to DBA/2 or C3H/HeJ males showed reduced fertility, perhaps due to failure of pregnancy immediately after the stress, but this was not corrected by alloimmunization with either DBA/2 [class I + class II major histocompatibility complex (MHC) immunogen] or C3H/HeJ (class I MHC immunogen) splenocytes. There was a reduction in the endogenous resorption rate, however, and implantation number was slightly increased by preimmunization using DBA/2 cells. The abortion rate could be boosted, however, by ultrasonic noise stress of high abortion rate CBA/J, and preimmunization using BALB/c (H-2d) splenocytes protected. A similar boosting of loss in low abortion rate BALB/k mice was ameliorated (albeit not completely) by preimmunization with allogenic paternal but not syngeneic splenocytes. CONCLUSIONS: Immunotherapy may protect against a variety of potential triggers of spontaneous abortion, including those that may be amenable to psychological remedies, and possible mechanisms are discussed.

Abortion, Spontaneous↗
PubMed1993

Murine trophoblast failure and spontaneous abortion.

PROBLEM: Infection has been proposed to initiate abortion, and the role of viruses in spontaneous resorption in mice has not been tested. METHOD: The anti-viral drug ribavirin (1-beta-D-ribofuranosyl-1,2,4-triazole-3-carboxamide) was fed to CBA/J and C3H/HeJ female mice beginning on the morning after mating with DBA/2J males. RESULTS: Ribavirin treatment increased the rate of abortion (resorption) on day 13.5, and this was associated with retardation of the rate of embryo development and hypoplasia of the trophoblast. There was a reduction in trophoblast-dependent decidua-associated soluble suppressor activity, but there was no maternal mononuclear cell infiltrate of the type reported in association with resorption of semiallogeneic and xenogeneic mouse embryos. This may be due to an immunosuppressive effect of ribavirin. Ribavirin was able to potently suppress proliferation of mouse trophoblast and mastocytoma cell lines in vitro. CONCLUSIONS: There are several drug-induced murine abortion models that provide useful insights into potential mechanisms underlying spontaneous pregnancy failure, but in the ribavirin mode, a direct impairment of trophoblast development appears to be responsible.

Abortion, Spontaneous↗
PubMed1993

Urinary nitrite excretion in premature infants: effects of transfusion or indomethacin.

Urinary nitrite excretion, an index of L-arginine-dependent nitric oxide formation, was quantified daily for two weeks, in very low-birth-weight (< 1500 g) premature infants. A transient 52% reduction in nitrite excretion was noted on the day of transfusions (54 +/- 10 versus 26 +/- 6 mumol/mmol creatinine, before and during transfusion, respectively, n = 24, p < 0.02). Indomethacin administration in six infants was associated with a dramatic increase in nitrite excretion from a basal median value of 3 to 76 mumol/mmol creatinine (p < 0.05). Nitrite excretion returned to baseline on day 3 after indomethacin administration. In two infants who received indomethacin and transfusions on the same day, the stimulatory effect on nitrite excretion by indomethacin overwhelmed any depressive effect of transfusions. These results suggest that L-arginine utilization is influenced by common therapeutic strategies in these high-risk infants.

Blood Component Transfusion↗
PubMed1993

Substance P levels in experimental ileitis in guinea pigs: effects of misoprostol.

Substance P, a neuropeptide mediator of inflammation, was quantified during the evolution of trinitrobenzene sulfonic acid (TNBS)-induced ileitis in guinea pigs. Ileitis was induced by a single intraluminal injection of TNBS (30 mg/kg in 50% ethanol). Misoprostol, a prostaglandin E1 analogue, was administered parenterally (30 mg/kg sc twice daily) in a group of TNBS-treated animals. Control guinea pigs received intraluminal saline (sham) or 50% ethanol (TNBS vehicle). Guinea pigs were evaluated at day 1, 3, 7, 14, or 30 after ileitis induction for substance P content (radioimmunoassay) and distribution (immunohistochemistry), morphology, myeloperoxidase (MPO) activity, and protein leak into the gut lumen. TNBS administration caused an increase in ileal MPO activity that peaked at day 7 and increased mucosal leak of protein. Misoprostol attenuated the granulocyte infiltration (MPO) response to TNBS but exacerbated the mucosal leak of protein. Substance P levels in whole ileal segments were unaltered from baseline on day 1 in all groups. On day 3 a marked decrease in ileal substance P content was evident in the TNBS and TNBS + misoprostol groups. As early as day 1, immunohistochemistry suggested that the decreased substance P content was confined to the mucosa and submucosa, because myenteric plexus staining was not reduced. Loss of staining in the perivascular nerves was particularly marked. Substance P content and distribution returned to baseline by day 30 post-TNBS, although MPO activity remained slightly elevated. We concluded that TNBS ileitis is associated with a marked reduction in mucosal and submucosal substance P content in parallel with the inflammatory response. Although misoprostol attenuated granulocyte infiltration in this model, it did not prevent the disturbances in enteric substance P or mucosal protein leak.

Animals↗
PubMed1993

Nitric oxide release in response to gut injury.

We evaluated nitric oxide release in several models of intestinal inflammation through luminal nitrite concentrations. In anesthetized rabbits, piglets, and guinea pigs, luminal lavages were collected from loops of normal or injured small intestine. Lavages were analyzed spectrophotometrically for nitrite (Griess reagent) and protein. Myeloperoxidase (MPO) content of intestinal segments was used as an index of granulocyte infiltration and intestinal inflammation. Acute ileal inflammation was induced by luminal acetic acid + casein in rabbits and luminal deoxycholate in neonatal piglets and adult rabbits. Chronic ileitis was induced in guinea pigs by intraluminal trinitrobenzenesulfonic acid. In each model nitrite levels in ileal lavages were significantly greater than control loops/animals. Increased luminal protein and intestinal MPO activity paralleled the changes in nitrite levels. To determine whether nitric oxide production influenced mucosal repair, segments of ileum were perfused with the L-arginine antagonist NG-nitro-L-arginine methyl ester (L-NAME, 10 mg/ml) after acute acetic acid + casein exposure. L-NAME administration reversed the decline in epithelial permeability characteristic of epithelial restitution, causing an increase in epithelial permeability which was readily reversible. These results suggest that nitrite production is a useful index of gut injury and that nitric oxide may contribute to the functional repair of the epithelial barrier under acute conditions.

Animals↗
PubMed1993

Protein topology prediction through parallel constraint logic programming.

In this paper, two programs are described (CBS1e and CBS2e). These are implemented in the parallel constraint logic programming language ElipSys. These predict protein alpha/beta-sheet and beta-sheet topologies from secondary structure assignments and topological folding rules (constraints). These programs illustrate how recent developments in logic programming environments can be applied to solve large-scale combinatorial problems in molecular biology. We demonstrate that parallel constraint logic programming is able to overcome some of the important limitations of more established logic programming languages i.e. Prolog. This is particularly the case in providing features that enhance the declarative nature of the program and also in addressing directly the problems of scaling-up logic programs to solve scientifically realistic problems. Moreover, we show that for large topological problems CBS1e was approximately 60 times faster than an equivalent Prolog implementation (CBS1) on a sequential device with further performance enhancements possible on parallel computer architectures. CBS2e is an extension of CBS1e that addresses the important problem of integrating the use of uncertain (weighted) protein folding constraints with categorical ones, through the use of a cost function that is minimized. CBS2e achieves this with a relatively minor reduction of performance. These results significantly extend the range and complexity of protein structure prediction methods that can reasonably be addressed using AI languages.

Artificial Intelligence↗
PubMed1993

Amelioration of chronic ileitis by nitric oxide synthase inhibition.

Nitric oxide synthesis appears to be elevated in inflammatory bowel disease, but little is known about the contribution of nitric oxide to the pathophysiological process. To address this issue, we included the nitric oxide synthase inhibitor, NG-nitro-L-arginine methyl ester (L-NAME) in the drinking water (10 or 100 micrograms/ml) of guinea pigs immediately after induction of ileitis by intraluminal trinitrobenzenesulfonic acid (TNBS 30 mg/kg in 50% ethanol). Guinea pigs were sacrificed after 7 days of this ad libitum treatment. Control groups received either intraluminal TNBS, saline or ethanol (TNBS vehicle) without L-NAME or TNBS + D-NAME (100 micrograms/ml), the inactive enantiomer. Immediately before sacrifice, guinea pigs were anesthetized and saline was administered intraluminally at the site of TNBS or saline administration and then withdrawn after 30 min. Change in lavage volume and lavage protein and nitrite levels were measured, as well as tissue myeloperoxidase and bowel wall thickness (weight/length). TNBS administration resulted in an increase in tissue thickness, myeloperoxidase and lavage protein and nitrite levels over sham controls. Oral L-NAME prevented these responses. D-NAME was ineffective with the exception of tissue thickness. The change in intestinal lavage fluid volume indicated that reabsorptive processes dominated in the sham and TNBS + L-NAME groups, and secretory responses predominated in TNBS and TNBS + D-NAME animals. In contrast to TNBS-induced ileitis, L-NAME (100 micrograms/ml, p.o., 7 days) administration to intact animals resulted in a local inflammatory response (i.e., increased myeloperoxidase activity and a fluid secretory response).(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Oxidoreductases↗
PubMed1993

Cytokines, decidua, and early pregnancy.

Cytokines and other small signalling molecules appear to play important roles in determining the success or failure of early pregnancy. Much more information is needed, particularly with respect to interaction effects of the multiple cytokines present in situ and matrix molecules. Further, this author would like to emphasize the importance of experiments which test in vivo the physiologic relevance of factors detected in samples of reproductive tissues using in vitro methods, existentialism notwithstanding.

Animals↗