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Biomedical subjects

M J Stafford

Publications and source records attributed to M J Stafford.

16 recordsLinked to original sources
PubMed2001

Signalling events underlying platelet aggregation induced by the glycoprotein VI agonist convulxin.

We have investigated the role of secretion and intracellular signalling events in aggregation induced by the glycoprotein (GP)VI-selective snake venom toxin convulxin and by collagen. We demonstrate that aggregation induced by threshold concentrations of convulxin undergoes synergy with ADP acting via the P2Y12 receptor whereas there is no synergy via the P2Y1 receptor or with thromboxanes. On the other hand, apyrase, the P2Y12 receptor antagonist, AR-C67085, and indomethacin only marginally inhibit aggregation induced by convulxin. In comparison, these inhibitors severely attenuate the response to collagen. In order to investigate whether the weak inhibitory action against convulxin is due to release of agonists other than ADP from dense granules, experiments were performed on murine platelets deficient in this organelle (pearl mice platelets). A slightly greater reduction in aggregation induced by convulxin was observed in pearl platelets than in the presence of inhibitors of ADP, but a maximal response was still attained. Importantly, inhibition of protein kinase C further reduced the response to convulxin in pearl platelets demonstrating a direct role for the kinase in aggregation. Chelation of intracellular Ca2+ with 1,2-bis(2-aminophenoxy)ethane-N,N,N,N',N'-tetraacetic acid (acetoxymethyl)ester (BAPTA-AM) abolished aggregation induced by convulxin under all conditions. Activation of phospholipase C by convulxin was potentiated by ADP acting through the P2Y12 receptor. In conclusion, we show that Ca2+ and protein kinase C, but not release of the secondary agonists ADP and thromboxane A2, are required for full aggregation induced by convulxin, whereas the response induced by collagen shows a much greater dependence on secretion of secondary agonists.

Adenosine Diphosphate↗
PubMed2001

Signalling components underlying platelet aggregation to a Ca2+ ionophore and a phorbol ester.

Although it is well established that G(q)- and G(i)-coupled receptors can combine to mediate platelet aggregation, the signalling events underlying the synergy are not fully characterised. This study has used the calcium ionophore, A23187, and phorbol ester, PMA, to investigate this question. We show that aggregation to submaximal but not maximal concentrations of ionophore is partially inhibited by antagonism of the P2Y(12) ADP receptor or PKC blockade. However, a full aggregation response can be restored under these conditions by addition of PMA or ADP. Studies using PI 3-kinase inhibitors demonstrate that this is the second messenger pathway that restores aggregation by the G(i)-coupled receptor in the presence of PKC blockade. However, under normal circumstances, PI 3-kinase activity is not a major requirement for aggregation to the ionophore. PMA stimulates a weak aggregation which takes several minutes to reach a maximum. Threshold concentrations of PMA and a G(i)-coupled receptor agonist when added alone show no effect on aggregation, but when combined induce aggregation responses. This study demonstrates that calcium and PKC interact synergistically with a G(i)-coupled receptor agonist to mediate aggregation, and also with each other. Activation of G(i) supports aggregation in part through the PI 3-kinase pathway. High concentration of ionophore on their own can induce aggregation independent of PKC and activation of G(i). Multiple signalling pathways mediate platelet aggregation and their relative importance depends on experimental conditions.

Adenosine Diphosphate↗
PubMed1991

Dual-chamber cardiac pacemakers.

Dual-chamber cardiac pacing provides distinct advantages over single-chamber systems, namely atrioventricular synchrony, improved cardiac output, and prevention of pacemaker syndrome. Providing nursing care to patients with dual-chamber pacemakers demands an understanding of basic cardiac pacing and of the unique features of dual-chamber systems. This knowledge is essential in evaluating pacemaker function, relating it to the patient's condition, and intervening appropriately in the face of complex paced rhythms.

Cardiac Pacing, Artificial↗
PubMed1987

Monitoring patients with permanent cardiac pacemakers.

Patients requiring cardiac pacing are predominantly older citizens with multiple problems, demanding highly skilled monitoring as well as a holistic approach to their care. Pacemaker therapy, though widely accepted, currently is being scrutinized to determine its impact on cost as well as quality. To this end, a Joint American College of Cardiology/American Heart Association Task Force established a subcommittee on pacemaker implantation to define current indications for permanent cardiac pacemakers. The indications have been grouped into three classifications. Class I: conditions for which there is general agreement that permanent pacemakers should be implanted. Class II: conditions for which permanent pacemakers are frequently used but for which there is divergence of opinion with respect to the necessity of their insertion. Class III: conditions for which there is general agreement that pacemakers are unnecessary. It behooves the nurse in clinical practice to review the reference related to the foregoing classification system and to be knowledgeable of the conditions that fall within each group.

Aged↗
PubMed1985

An office laboratory panel to assess vaginal problems.

In determining the cause of vaginal complaints, the routine use of four simple tests ("the vagina panel") enables the physician to identify pathogens (Candida, Gardnerella, Trichomonas), pathologic processes (inflammation, estrogen deficiency) and, in most instances, a healthy vagina. Time and money are saved. The specimens can be collected in one minute during a pelvic examination. The panel can provide the answers to eight essential questions in two minutes of observer time, with supplies costing about $2.

Adult↗
PubMed1984

Ventrolateral medullary surface blood flow determined by hydrogen clearance.

The H2 clearance technique was used to determine the blood flow of the postulated respiratory chemosensitive areas near the ventrolateral surface of the medulla. In 12 pentobarbital sodium-anesthetized cats, flow (mean +/- SD) was measured from 25-micron Teflon-coated platinum wire electrodes implanted to a depth of 0.3-0.7 mm. Flow (in ml X min-1 X 100 g-1, n = 35) was 52.8 +/- 28.5 in hypocapnia [arterial CO2 partial pressure (PaCO2) = 21.8 +/- 1.6 Torr], 57.8 +/- 27.5 in normocapnia (PaCO2 = 31.9 +/- 2.2 Torr), and 75.0 +/- 31.7 in hypercapnia (PaCO2 = 44.5 +/- 3.0 Torr). Flow determined from 15 electrodes in adjacent pyramidal tracts (white matter) was less at all levels of CO2; 22.9 +/- 12.3 in hypocapnia, 29.1 +/- 15.9 in normocapnia, and 33.9 +/- 13.9 in hypercapnia. In hypoxia [arterial O2 partial pressure (PaO2) = 39.9 +/- 6.3 Torr] ventrolateral surface flow rose to 87.9 +/- 47.6, and adjacent white matter flow was 35.8 +/- 15.6. These results indicate that flow in the postulated central chemoreceptor areas exceeds that of white matter and is sensitive to variations in PaCO2 and PaO2.

Animals↗
PubMed1983

Colonization of Candida albicans in vagina, rectum, and mouth.

To better understand the frequency of appearance, the density of growth, and the most common sites in which female patients harbor Candida albicans, a study was initiated of all patients receiving a pelvic examination for any reason at a solo family practice office. From February 1980 to November 1981, 341 pelvic examinations were accompanied by cultures and colony counts of the vagina, rectum, and mouth. A semiquantitative method adapted to Microstix-Candida (Ames Company) was utilized. Only 39 percent of all examinations had negative cultures in all three sites. Twenty-three percent of the positive cultures for C albicans were found from the vagina, 41 percent from the rectum, and 34 percent from the mouth. Incidence of colonization in any site did not vary significantly from 16 to 75 years of age. Negative rectal colonization was associated with lower vaginal colony counts and less frequent vaginal symptomatology. Relatively high vaginal colony count was associated with symptomatic vaginal candidiasis.

Adolescent↗
PubMed1982

No effect of naloxone on hypoxia-induced ventilatory depression in adults.

The ventilatory response to acute isocapnic hypoxia is prompt but is not maintained at its peak. Within 10 min, it begins to fall, and by 30 min has reached an approximately steady level, usually still above control. We used naloxone to test in four men the hypothesis that this fade is hypoxic depression mediated by endogenous opioid peptides, e.g, endorphins. Breath by breath minute ventilation was recorded during a hyperoxic control period (FIO2 = 0.3) to establish control alveolar PCO2. After 15 min. of isocapnic hypoxia (end-tidal PO2 = 45 Torr), naloxone injection (1.2 or 10 mg, iv) failed to alter the slow decrement of ventilation. Hypoxic ventilatory depression appears not to be mediated by endorphins in adults.

Double-Blind Method↗
PubMed1980

Relationship of CSF pH, O2, and CO2 responses in metabolic acidosis and alkalosis in humans.

The effect of induced metabolic acidosis (48 h of NH4Cl ingestion, BE - 10.6 +/- 1.1) and alkalosis (43 h of NaHCO3- ingestion BE 8.8 +/- 1.6) on arterial and lumber CSF pH, Pco2, and HCO3- and ventilatory responses to CO2 and to hypoxia was assessed in five healthy men. In acidosis lumbar CSF pH rose 0.033 +/- 0.02 (P less than 0.05). In alkalosis CSF pH was unchanged. Ventilatory response lines to CO2 at high O2 were displaced to the left in acidosis (9.0 +/- 1.4 Torr) and to the right in alkalosis (4.5 +/- 1.5 Torr) with no change in slope. The ventilatory response to hypoxia (delta V40) was increased in acidosis (P less than 0.05) and it was decreased in four subjects in alkalosis (P, not significant). We conclude that the altered ventilatory drives of steady-state metabolic imbalance are mediated by peripheral chemoreceptors, and in acidosis the medullary respiratory chemoreceptor drive is decreased.

Acidosis↗
PubMed1979

A two temperature, two PO2 method of estimating the determinants of tcPO2.

We have prepared an algorithm describing the relationship of tcPO2 to PaO2 and used this with measured values of both tcPO2 and PaO2 under four conditions (two PO2 levels, two temperatures) to generate four equation sets that yielded unique solutions for the four unknown parameters. In adults under a 44 degree C electrode, capillary temperature averaged about 43 degrees C, O2 consumption about 0.0042 ml/gm/min, blood flow about 0.64 ml/gm/min, and diffusion gradient, D, about 32 mm Hg. We have not attempted to define these values in premature or normal newborn infants, because the method requires about one hour of exposure to 100% O2.

Adult↗