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Biomedical subjects

D Campbell

Publications and source records attributed to D Campbell.

At least 181 records · Page 10Linked to original sources

Long-term neuropsychological sequelae of fever associated with amnesia.

It has been well established that high fever can cause substantial damage to the cerebellum and also cause multiple small vascular lesions in neocortex and subcortical white matter. Beyond acute effects, the neuropsychological sequelae of these latter cortical and subcortical lesions have not been studied. The investigation reported involved 36 VA patients with a history of serious febrile illness. The febrile illnesses of the pyrexic subjects did not cause febrile seizures and resulted from diseases that did not directly involve the brain (e.g., encephalitis, meningitis, malaria). Control subjects were combat veterans who had suffered gunshot wounds, but who had no history of febrile illness. Pyrexic patients performed worse than controls on a variety of measures including language, memory, concentration, and word finding as well as failing a test of dichotic listening for words. Results demonstrate that hyperpyrexia can have lasting neuropsychological sequelae, and suggest that history of serious febrile illness be considered as an exclusionary criterion for participation in neuropsychological research concerning other topics or disorders.

Journal Article↗

The effects of bedrest on circadian changes in hemostasis.

Venous stasis occurs when people are at bedrest, because of altered venous flow characteristics. This is commonly believed to be one etiology behind the development of deep venous thrombosis (DVT). The hemostatic effects of bedrest and their possible role in DVT development have not been fully examined. We hypothesized that bedrest would lead to increases in hemostatic function and that these increases could be important in the development of DVT. Twelve non-smoking volunteers were studied during supine positioning for 36 hours. Platelet reactivity and plasma concentrations of fibrinogen, alpha 2-antiplasmin, plasminogen, thromboxane beta 2, plasminogen activator inhibitor-1, tissue plasminogen activator and neuroendocrine hormones (cortisol, epinephrine and norepinephrine) were measured at 8:00 a.m., 10:00 a.m., 4:00 p.m. and 8:00 a.m. Cortisol demonstrated an early morning increase while catecholamines were unchanged throughout. Fibrinogen, alpha 2-antiplasmin, plasminogen and platelet reactivity were no different at any time point. Fibrinolytic proteins changed over time, manifested by decreased PAI-1 antigen and activity levels at 24 h. Based upon the parameters measured, bedrest causes no increase in hemostatic function. In fact, bedrest causes the potential for enhanced fibrinolysis, that differs from that previously reported for normal activity over 24 h. This may represent a protective mechanism to counter the effects of stasis from bedrest.

Adolescent↗

Initial effects of the grounding of the tanker Braer on health in Shetland. The Shetland Health Study Group.

OBJECTIVE: To determine if the oil spillage from the tanker Braer had any immediate health effects on the exposed resident population. DESIGN: Cohort study with a comparison against controls, exposure status being assigned on the basis of geographical location. SETTING: Rural Shetland. SUBJECTS: All those resident on or after 5 January 1993 (day 0) within 4.5 km of the site of tanker's grounding. Controls matched for sex and age were drawn from a general practice list 95 km distant. OUTCOME MEASURES: Demographic details; smoking and alcohol consumption; perception of health and reported presence or absence of specific symptoms; peak expiratory flow; results of haematology, liver and renal function tests, and blood and urine toxicology. RESULTS: Of subjects contacted, 420 (66%) exposed people and 92 (68%) controls were studied; 56 non-attenders were surveyed. Principal health effects arose on days 1 and 2 and were headache, throat irritation, and itchy eyes. No significant differences between those exposed and controls were found for any of the biological markers. Toxicological studies did not show any exposures that are known to affect human health. CONCLUSIONS: The study confirmed the anecdotal reports of certain acute symptoms. No evidence of pulmonary, haematological, renal, or hepatic damage was detected at the population level. Toxicological samples from exposed people did not find levels known to affect human health. Further studies are required to ascertain whether there have been any long term effects on the population.

Acute Disease↗

Structure of the CAMPATH-1 antigen, a glycosylphosphatidylinositol-anchored glycoprotein which is an exceptionally good target for complement lysis.

CAMPATH-1 antibodies recognize a unique molecule on human lymphocytes and are unusually efficient at causing cell lysis with homologous complement. They have been successfully used for lymphocyte depletion in vivo in a variety of diseases. We find that the antigen is a very small glycosylphosphatidylinositol (GPI)-anchored glycoprotein with a mature peptide comprising only 12 amino acids. It can be separated into two distinct antigenic fractions which differ in their susceptibility to phosphatidylinositol-specific phospholipase C. There is one N-linked glycosylation site, but no evidence for O-glycosylation despite the presence of several serine and threonine residues. The antibodies were found to bind, albeit with a generally reduced affinity, to a proteolytic fragment containing the C-terminal tripeptide and the GPI anchor. We postulate that one of the reasons why the CAMPATH-1 antibodies are so good for cell lysis is because they bind to an epitope which is likely to be very close to the lipid bilayer.

Amino Acid Sequence↗

Antibodies to murine CD40 stimulate normal B lymphocytes but inhibit proliferation of B lymphoma cells.

A rat anti-mouse CD40 antiserum has been prepared by hyperimmunisation of Lewis rats with a highly purified preparation of the recombinant extracellular domain of murine CD40. This antiserum specifically binds CD40-expressing L cell transfectants, but not untransfected L cells, and induces vigorous proliferation of highly purified small dense B cells obtained from the spleens of unstimulated mice. Anti-CD40-induced B cell proliferation can be augmented by the addition of IL-4 and is inhibited by purified recombinant soluble mouse CD40. Interestingly the same anti-CD40 antiserum specifically inhibits the in vitro growth of A.20 murine B lymphoma cells. The specificity of this inhibition can be demonstrated by reversing the effect with purified recombinant soluble mouse CD40. These data implicate CD40 as a possible target for therapeutic intervention in the treatment of B lymphomas.

Animals↗

Networking with mitogen-activated protein kinases.

Mitogen activated protein (MAP) kinases and their target ribosomal protein S6 (RSK) kinases have been recognized as shared components in the intracellular signaling pathways of many diverse cytokines. Recent studies have extended this protein kinase cascade by identifying the major activator of vertebrate MAP kinases as a serine/threonine/tyrosine-protein kinase called MEK, which is related to yeast mating factor-regulated protein kinases encoded by the STE7 and byr1 genes. MEK, in turn, may be activated following its phosphorylation on serine by either of the kinases encoded by proto-oncogenes raf1 or mos, as well as by p78mekk, which is related to the yeast STE11 and byr2 gene products. Isoforms of all of these protein kinases may specifically combine to assemble distinct modules for intracellular signal transmission. However, the fundamental architecture of these protein kinase cascades has been highly conserved during eukaryotic evolution.

Animals↗

Production of TNF alpha by LPS-stimulated murine, rat and human blood and its pharmacological modulation.

Tumour necrosis factor alpha (TNF alpha) has been reported to play a key role in the pathogenesis of sepsis and chronic inflammatory diseases, including rheumatoid arthritis and atherosclerosis, suggesting that agents which inhibit TNF alpha production may have therapeutic utility for the treatment of such conditions. Production of TNF alpha by LPS (lipopolysaccharide)-stimulated murine, rat and human heparinized blood was investigated. LPS (1-100 micrograms/ml) caused a similar concentration- and time-dependent stimulation of TNF alpha production by rat and human blood, achieving levels of 750-5000 U/ml (L929 bioassay) at 6 h. In contrast, TNF alpha production by LPS-stimulated murine blood was poor and variable (0-150 U/ml). Dexamethasone and pentoxifylline caused a concentration-dependent inhibition of TNF alpha production by LPS-stimulated human and rat blood with IC50s of 0.26 +/- 0.05 and 73.0 +/- 26.4 microM for human and 5.7 +/- 1.8 nM and 20.6 +/- 8.0 microM for rat blood, respectively. Therefore, LPS-stimulated rat and human, but not murine, blood are suitable systems for the detection and evaluation of inhibitors of TNF alpha production.

Animals↗

Differential development of the stress response in congenital learned helplessness.

Early in the development of the hypothalamic-pituitary-adrenal (HPA) axis, the rat undergoes a stress hyporesponsive period of blunted responses to several stressors including cold exposure (CE) and maternal deprivation (MD). We examined the development of the axis by monitoring adrenocorticotropin hormone (ACTH) plasma levels in an animal model of depression and/or anxiety characterized by learned helpless (LH) behavior and a dysfunctional HPA axis in adult life. On postnatal day 7 there was no significant difference in basal plasma ACTH levels between congenital (cLH) and controls, but cLH animals showed a blunted response to CE (P < 0.001). By postnatal day 14 there was a dramatic increase in ACTH response to CE (P < 0.005). On postnatal day 21 baseline ACTH and response to CE were again significantly suppressed in cLH rats. Stress responsiveness to MD was present in all groups and was insignificantly different for all ages of development between groups. These findings suggest that rats with congenital learned helplessness undergo a differential response in the development of the HPA axis in that the axis was hypersensitive at postnatal day 14 and became hyporesponsive beyond day 14, and this may, in part, account for the dysfunctional stress response observed during adulthood.

Adrenocorticotropic Hormone↗

Perioperative platelet reactivity and the effects of clonidine.

BACKGROUND: Increased postoperative platelet reactivity may contribute to arterial thrombotic complications following surgery. alpha 2 Agonists, which are being used increasingly to blunt the stress response of surgery, increase platelet aggregation in vitro. We compared perioperative changes in platelet reactivity in 21 patients receiving either clonidine or placebo. METHODS: Patients undergoing major abdominal surgery were randomized to receive oral and transdermal clonidine (n = 11) or placebo (n = 10). All patients received similar perioperative management, including preoperative sedation, general anesthesia without neuraxial opioids, or local anesthetics and postoperative patient-controlled intravenous morphine. Blood was obtained for measurement of clonidine level, fibrinogen concentration, platelet count, and platelet reactivity (impedance aggregometry and dense granule release) before induction and 24, 48, and 72 h postoperatively. RESULTS: Thirteen of the 21 patients had biopsy-proven cancer at surgery, 5 of 11 received clonidine and 8 of 10 received placebo (NS). Clonidine levels were therapeutic (1-2 ng/ml) throughout the study period. Clonidine administration had no effect on platelet count or platelet reactivity. Therefore, the groups were combined for further analysis. In this group (n = 21), compared to preoperative values, fibrinogen levels rose maximally (36%) at 72 h postoperatively and platelet counts decreased 22% at 48 h. Platelet reactivity (aggregation and degranulation) to collagen, adenosine diphosphate, arachidonic acid, and ristocetin, increased at 24, 48, and 72 h postoperatively. Thrombin-induced (supramaximal stimulus) dense granule release did not change from preoperative values. CONCLUSIONS: These data indicate that major abdominal surgery causes increased platelet reactivity postoperatively but does not effect maximal degranulation. This increased platelet reactivity occurs within 48 h of surgery, coinciding with the peak incidence of postoperative arterial thrombotic complications. Clonidine administration has no effect on surgically induced changes in platelet reactivity. In this surgical patient population, the use of clonidine should not increase the risk of platelet-induced perioperative arterial thrombosis.

Abdomen↗

Clinical birthweight standards for a total population in the 1980s.

OBJECTIVE: To derive clinical standards for singleton birthweight in a population based on area of residence. DESIGN: Analysis of variables recorded in Aberdeen Maternity and Neonatal Databank, calculating for each birth a standardised birthweight score, taking account of determining factors. SUBJECTS: All singleton live births of 32 to 42 weeks gestation to Aberdeen City District residents from 1979 to 1983. RESULTS: Basic standards of birthweight are presented correcting for gestational age, sex of the baby and parity of the mother. Birthweight is not normally distributed and empirical data are presented rather than smoothed curves. Adjustment for maternal height is straightforward but adjustment for maternal weight must take account of the gestation at which the woman was weighed. A method of calculating the appropriate correction for height and weight is described in detail. CONCLUSION: Birthweight is not normally distributed at each week of gestation. Standardisation for parity, gestation and sex of the baby is essential, but adjustment for maternal size is complex.

Birth Weight↗

Violence and abuse of women: a perinatal health care issue.

This article discusses the perinatal health issue of abuse directed at pregnant women by their intimate partners. The incidence, prevalence, and severity of intimate violence during pregnancy are presented, as is a discussion of the possible health disruptions that can occur as a result of violence and abuse. Nursing interventions for abused pregnant women are presented within a framework of advocacy and empowerment. Strategies for primary prevention are outlined, and methods of secondary and tertiary intervention are discussed. The article concludes with a discussion of culturally relevant practice for abused women.

Cultural Characteristics↗

Helping people help themselves.

With the growing consumer participation movement and the emphasis in health care shifting from hospital to community, the term community development is cropping up more and more. Yet the concept of community development has always been integral to public health nursing. Simply put, community development is a process by which a community identifies its needs and assumes ownership of decision-making and subsequent action surrounding those needs. By integrating community development principles into their work with two neighboring communities, nurses with Calgary Health Services facilitated the establishment of a much-needed parent support group.

Community Participation↗

Identification of epidermal growth factor Thr-669 phosphorylation site peptide kinases as distinct MAP kinases and p34cdc2.

A synthetic peptide modeled after the major threonine (T669) phosphorylation site of the epidermal growth factor (EGF) receptor was an efficient substrate (apparent Km approximately 0.45 mM) for phosphorylation by purified p44mpk, a MAP kinase from sea star oocytes. The peptide was also phosphorylated by a related human MAP kinase, which was identified by immunological criteria as p42mapk. Within 5 min of treatment of human cervical carcinoma A431 cells with EGF or phorbol myristate acetate (PMA), a greater than 3-fold activation of p42mapk was measured. However, Mono Q chromatography of A431 cells extracts afforded the resolution of at least three additional T669 peptide kinases, some of which may be new members of the MAP kinase family. One of these (peak I), which weakly adsorbed to Mono Q, phosphorylated myelin basic protein (MBP) and other MAP kinase substrates, immunoreacted as a 42 kDa protein on Western blots with four different MAP kinase antibodies, and behaved as a approximately 45 kDa protein upon Superose 6 gel filtration. Another T669 peptide kinase (peak IV), which bound more tightly to Mono Q than p42mapk (peak II), exhibited a nearly identical substrate specificity profile to that of p42mapk, but it immunoreacted as a 40 kDa protein only with anti-p44mpk antibody on Western blots, and eluted from Superose 6 in a high molecular mass complex of greater than 400 kDa. By immunological criteria, the T669 peptide kinase in Mono Q peak III was tentatively identified as an active form of p34cdc2 associated with cyclin A. The Mono Q peaks III and IV kinases were modestly stimulated following either EGF or PMA treatments of A431 cells, and they exhibited a greater T669 peptide/MBP ratio than p42mapk. These findings indicated that multiple proline-directed kinases may mediate phosphorylation of the EGF receptor.

Amino Acid Sequence↗

Characterization of a type II collagen gene (COL2A1) mutation identified in cultured chondrocytes from human hypochondrogenesis.

A subtle mutation in the type II collagen gene COL2A1 was detected in a case of human hypochondrogenesis by using a chondrocyte culture system and PCR-cDNA scanning analysis. Chondrocytes obtained from cartilage biopsies were dedifferentiated and expanded in monolayer culture and then redifferentiated by culture over agarose. Single-strand conformation polymorphism and direct sequencing analysis identified a G----A transition, resulting in a glycine substitution at amino acid 574 of the pro alpha 1(II) collagen triple-helical domain. Morphologic assessment of cartilage-like structures produced in culture and electrophoretic analysis of collagens synthesized by the cultured chondrocytes suggested that the glycine substitution interferes with conversion of type II procollagen to collagen, impairs intracellular transport and secretion of the molecule, and disrupts collagen fibril assembly. This experimental approach has broad implications for the investigation of human chondrodysplasias as well as human chondrocyte biology.

Alleles↗