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Biomedical subjects

K Harvey

Publications and source records attributed to K Harvey.

At least 19 recordsLinked to original sources
PubMed2001

Reducing violence in severe mental illness: randomised controlled trial of intensive case management compared with standard care.

OBJECTIVES: To establish whether intensive case management reduces violence in patients with psychosis in comparison with standard case management. DESIGN: Randomised controlled trial with two year follow up. SETTING: Four inner city community mental health services. PARTICIPANTS: 708 patients with established psychotic illness allocated at random to intervention (353) or control (355) group. INTERVENTION: Intensive case management (caseload 10-15 per case manager) for two years compared with standard case management (30-35 per case manager). MAIN OUTCOME MEASURE: Physical assault over two years measured by interviews with patients and case managers and examination of case notes. RESULTS: No significant reduction in violence was found in the intensive case management group compared with the control group (22.7% v 21.9%, P=0.86). CONCLUSIONS: Intensive case management does not reduce the prevalence of violence in psychotic patients in comparison with standard care.

Adult↗
PubMed2001

Docosahexaenoic acid induces apoptosis in Jurkat cells by a protein phosphatase-mediated process.

Docosahexaenoic acid (DHA) is an omega-3 fatty acid under intense investigation for its ability to modulate cancer cell growth and survival. This research was performed to study the cellular and molecular effects of DHA. Our experiments indicated that the treatment of Jurkat cells with DHA inhibited their survival, whereas similar concentrations (60 and 90 microM) of arachidonic acid and oleic acid had little effect. To explore the mechanism of inhibition, we used several measures of apoptosis to determine whether this process was involved in DHA-induced cell death in Jurkat cells. Caspase-3, an important cytosolic downstream regulator of apoptosis, is activated by death signals through proteolytic cleavage. Incubation of Jurkat cells with 60 and 90 microM DHA caused proteolysis of caspase-3 within 48 and 24 h, respectively. DHA treatment also caused the degradation of poly-ADP-ribose polymerase and DNA fragmentation as assayed by flow cytometric TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling) assay. These results indicate that DHA induces apoptosis in Jurkat leukemic cells. DHA-induced apoptosis was effectively inhibited by tautomycin and cypermethrin at concentrations that affect protein phosphatase 1 (PP1) and protein phosphatase 2B (PP2B) activities, respectively, implying a role for these phosphatases in the apoptotic pathway. Okadaic acid, an inhibitor of protein phosphatase 2A, had no effect on DHA-induced apoptosis. These results suggest that one mechanism through which DHA may control cancer cell growth is through apoptosis involving PP1/PP2B protein phosphatase activities.

Apoptosis↗
PubMed2001

Monocytes harbour replication-competent, non-latent HIV-1 in patients on highly active antiretroviral therapy.

OBJECTIVE: To determine whether HIV-1 can be recovered from blood monocytes as well as resting, memory CD4 T lymphocytes of patients on highly active antiretroviral therapy (HAART) with undetectable plasma viraemia and whether infection is active or latent. DESIGN: Five patients with plasma HIV-1-RNA levels of less than 500 copies/ml for at least 3 months and less than 50 copies/ml at the time of sampling were initially selected, followed by an additional five patients with viral loads of less than 50 copies/ml for 3 months or more. METHODS: Monocytes were isolated from blood by plastic adherence, then further purified by a second adherence step or CD3 depletion before co-culture with CD8-depleted donor peripheral blood mononuclear cells. Virus isolates were examined for mutations conferring resistance to reverse transcriptase or protease inhibitors and for genotype. The highly purified monocytes were also analysed for the presence of proviral and unintegrated viral DNA and multiply spliced (MS) viral mRNA by polymerase chain reaction. RESULTS: Virus was recovered from monocytes of five patients. Sequencing of the recovered viruses did not reveal multiple drug resistance, and was consistent with a non-syncytium-inducing/CCR5 phenotype. Proviral DNA was detectable in monocytes from all subjects, and unintegrated HIV-1 DNA and MS RNA was found in four out of five populations examined. CONCLUSION: Recovery of replication-competent virus from some HAART patients indicates that monocytes can also harbour HIV-1. Detection of circular, viral DNA and spliced RNA, albeit at very low levels, in these cells suggests that their infection is recent and transcriptionally active rather than latent.

Antiretroviral Therapy, Highly Active↗
PubMed2001

Relatives of patients with severe psychotic illness: factors that influence appraisal of caregiving and psychological distress.

BACKGROUND: Research shows considerable variability in the effect on relatives of patients' mental illness but the determinants of relatives' experience remain unclear. We investigated the influence of demographic, social and clinical characteristics on relatives' experience when conceptualised using a stress-appraisal-coping paradigm. METHODS: Our sample was drawn from relatives of patients recruited to the UK700 case management study (n = 154). Demographic, social and clinical data were collected from patients, and relatives completed the Experience of Caregiving Inventory and the General Health Questionnaire. We predicted that patients' symptomatology in particular would influence relatives' experience, and that relatives who appraised caregiving more negatively and less positively would experience greater psychological distress. RESULTS: Linear regression analyses revealed that relatives' appraisal was not predicted by patients' symptomatology. Instead, relatives appraised caregiving more negatively if the patient was unemployed or younger, and less positively if the patient had been ill for longer or had poorer social functioning. Little of the variance in appraisal was explained by these variables, however. Consistent with the stress-coping model, relatives' negative appraisal was a strong predictor of psychological distress and accounted for a substantial proportion of its variance. Positive appraisal did not predict psychological distress, however. None of the demographic, social or clinical characteristics tested had any significant effect on relatives' psychological distress once appraisal was adjusted for. There was an unexpected positive correlation between the two appraisal scales, with relatives who appraised caregiving more negatively also appraising it more positively. CONCLUSIONS: Our results support a stress-coping model of caregiving but further research is required to determine more influential predictors of relatives' appraisal. Our findings indicate that interventions aimed at patients' social functioning and relatives' negative appraisal of caregiving may assist in reducing relatives' psychological distress.

Adult↗
PubMed2001

Effect of phosphatidic acid on human breast cancer cells exposed to doxorubicin.

We previously demonstrated that phosphatidic acid (PA) induces chemotactic migration of highly metastatic breast cancer cells MDA-MB-231. The widely used anticancer drug doxorubicin was reported to induce apoptosis of cancer cells. Growth factors such as epidermal growth factor (EGF) and bioactive lipids such as lysophosphatidic acid (LPA) and sphingosine 1-phosphate (SPP) have been shown to enhance viability and to protect cancer cells against apoptosis. In this study, we investigated the effect of PA on MDA-MB-231 cells exposed to the anticancer drug doxorubicin. Cell migration toward PA was partially inhibited by doxorubicin treatment, and PA moderately diminished cell cycle arrest of cells exposed to doxorubicin. Although PA itself was not able to induce apoptosis of MDA-MB-231 cells, apoptosis of cells exposed to doxorubicin was markedly enhanced by PA treatment. Thus, PA is able to increase the apoptotic potential of doxorubicin, and may regulate the effects of doxorubicin used for chemotherapy.

Antibiotics, Antineoplastic↗
PubMed2001

Intellectual functioning and outcome of patients with severe psychotic illness randomised to intensive case management. Report from the UK700 trial.

BACKGROUND: Little research has been carried out on the benefits of intensive case management (ICM) for people with borderline IQ and severe mental illness. AIMS: To compare outcome and costs of care of patients with severe psychotic illness with borderline IQ to patients of normal IQ and to assess whether ICM is more beneficial for the former than for the latter. METHOD: The study utilises data from the UK700 multi-centre randomised controlled trial of case management. The main outcome measure was the number of days spent in hospital for psychiatric reasons. Secondary outcomes were costs of care and clinical outcome. RESULTS: ICM was significantly more beneficial for borderline-IQ patients than those of normal IQ in terms of reductions in days spent in hospital, hospital admissions, total costs and needs and increased satisfaction. CONCLUSIONS: ICM appears to be a cost-effective strategy for a subgroup of patients with severe psychosis with cognitive deficits.

Case Management↗
PubMed2001

Relatives of patients with severe psychotic disorders: factors that influence contact frequency. Report from the UK700 trial.

BACKGROUND: The isolation experienced by many patients with severe psychotic disorders is generally assumed to be due to their social withdrawal. An alternative possibility is that relatives avoid frequent contact with patients because they find the situation distressing. AIMS: To examine the predictors of frequent patient-relative contact, in particular the role of relatives' experience. METHOD: UK700 trial data were used to determine baseline predictors of frequent contact and establish whether relatives' experience at baseline predicted continued frequent contact 2 years later. RESULTS: Neither characteristics associated in the literature with relatives' 'burden' nor relatives' experience predicted patient-relative contact frequency. Instead, the predictors were mainly demographic. CONCLUSIONS: Many relatives experience considerable distress, but the evidence does not suggest that they avoid frequent contact with the patient as a consequence.

Adult↗
PubMed2001

Suicidal behaviour in psychosis: prevalence and predictors from a randomised controlled trial of case management: report from the UK700 trial.

BACKGROUND: It is unclear whether intensive case management influences the prevalence of suicidal behaviour in patients with psychosis. AIMS: To compare the effect of intensive case management and standard care on prevalence of suicidal behaviour in patients with chronic psychosis. METHOD: Patients with established psychosis (n = 708) were randomised either to intensive case management or to standard care. The prevalence of suicidal behaviour was estimated at 2-year follow-up and compared between treatment groups. Suicide attempters and non-attempters were compared on multiple socio-demographic and clinical variables to identify predictors of suicidal behaviour. RESULTS: There was no significant difference in prevalence of suicidal behaviour between treatment groups. Recent attempts at suicide and multiple recent hospital admissions best predicted future attempts. CONCLUSIONS: Intensive case management does not appear to influence the prevalence of suicidal behaviour in chronic psychosis. Predictors identified in this study confirm some previous findings.

Adolescent↗
PubMed2001

Child sexual abuse, poor parental care and adult depression: evidence for different mechanisms.

BACKGROUND: Child sexual abuse (CSA) and poor parental care (neglect and institutional care) are associated with depression in adult life. Little is known about possible mechanisms underlying these associations. AIMS: To examine the role of adult intimate-love relationships as differential mediators or moderators of the associations between CSA, poor parental care and adult depression. METHOD: Sampling was carried out in two phases. In the first, questionnaires were sent to women aged 25-36 years in five primary care practices. Second-phase subjects for interview (n=198) were drawn from three strata defined on the basis of childhood adversities. Recalled childhood experiences and recent adult relationships and depression were assessed and rated independently. Frequencies of predictor and response variables, effect estimates and their confidence intervals were weighted back to the general population questionnaire sample. RESULTS: The risk for depression associated with CSA was unaffected by quality of adult relationships, while the risk associated with poor parental care was substantially altered. CONCLUSIONS: There may be different pathways linking CSA and poor parental care to adult depression.

Adult↗
PubMed2000

Cutting edge: lipoxins rapidly stimulate nonphlogistic phagocytosis of apoptotic neutrophils by monocyte-derived macrophages.

Lipoxins (LX) are lipoxygenase-derived eicosanoids generated during inflammation. LX inhibit polymorphonuclear neutrophil (PMN) chemotaxis and adhesion and are putative braking signals for PMN-mediated tissue injury. In this study, we report that LXA4 promotes another important step in the resolution phase of inflammation, namely, phagocytosis of apoptotic PMN by monocyte-derived macrophages (Mphi). LXA4 triggered rapid, concentration-dependent uptake of apoptotic PMN. This bioactivity was shared by stable synthetic LXA4 analogues (picomolar concentrations) but not by other eicosanoids tested. LXA4-triggered phagocytosis did not provoke IL-8 or monocyte chemoattractant protein-1 release. LXA4-induced phagocytosis was attenuated by anti-CD36, alphavbeta3, and CD18 mAbs. LXA4-triggered PMN uptake was inhibited by pertussis toxin and by 8-bromo-cAMP and was mimicked by Rp-cAMP, a protein kinase A inhibitor. LXA4 attenuated PGE2-stimulated protein kinase A activation in Mphi. These results suggest that LXA4 is an endogenous stimulus for PMN clearance during inflammation and provide a novel rationale for using stable synthetic analogues as anti-inflammatory compounds in vivo.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2000

Platelet cryopreservation using a combination of epinephrine and dimethyl sulfoxide as cryoprotectants.

Current methods of platelet storage are unsatisfactory because of the short shelf life of platelets and the rapid loss of platelet viability. We have developed a cryopreservation method that results in less damage from freezing and higher recovered function of platelets. Platelets were cryopreserved using a combination of epinephrine (EPN) and dimethyl sulfoxide (Me(2)SO) as cryoprotectants. The response of platelets to agonists was studied by flow cytometry and aggregation tests. Cryopreserving platelets with Me(2)SO decreased platelet annexin V binding due to freezing. The combination of EPN with Me(2)SO enhanced Me(2)SO cryoprotection and decreased platelet microparticle generation, suggesting that cryopreserving platelets using this combination is associated with increased platelet integrity. Platelet cryopreservation with an Me(2)SO/EPN combination also increased platelet aggregability, which was demonstrated by decreasing the lag phase and increasing the aggregation density to 66.39% +/- 6.6 that of fresh platelet-rich plasmas. We conclude that adding EPN as a combined cryoprotectant improves the quality of Me(2)SO-frozen platelets. As a method of aggregation of cryopreserved platelets, this method is comparable to that of normal fresh platelets and may improve the conditions for platelet transfusion.

Annexin A5↗
PubMed2000

Sphingosine 1-phosphate released from platelets during clotting accounts for the potent endothelial cell chemotactic activity of blood serum and provides a novel link between hemostasis and angiogenesis.

Recent studies have identified factors responsible for angiogenesis within developing tumors, but mediators of vessel formation at sites of trauma, injury, and wound healing are not clearly established. Here we show that sphingosine 1-phosphate (S1P) released by platelets during blood clotting is a potent, specific, and selective endothelial cell chemoattractant that accounts for most of the strong endothelial cell chemotactic activity of blood serum, an activity that is markedly diminished in plasma. Preincubation of endothelial cells with pertussis toxin inhibited this effect of S1P, demonstrating the involvement of a Galphai-coupled receptor. After S1P-induced migration, endothelial cells proliferated avidly and differentiated forming multicellular structures suggestive of early blood vessel formation. S1P was strikingly effective in enhancing the ability of fibroblast growth factor to induce angiogenesis in the avascular mouse cornea. Our results show that blood coagulation initiates endothelial cell angiogenic responses through the release of S1P, a potent endothelial cell chemoattractant that exerts its effects by activating a receptor-dependent process.

Animals↗
PubMed1999

Diagnostic testing for serious bacterial infections in infants aged 90 days or younger with bronchiolitis.

OBJECTIVES: To describe the different laboratory tests that are performed on young infants aged 90 days or younger with bronchiolitis and to identify historical and clinical predictors of infants on whom laboratory tests are performed. DESIGN: Cross-sectional study whereby information was obtained by retrospective review of medical records from November through March 1992 to 1995 of all infants with a clinical diagnosis of bronchiolitis. SETTING: Urban pediatric emergency department. PATIENTS: Two hundred eleven consecutive infants aged 90 days or younger (median age, 54 days) with 216 episodes of bronchiolitis. MAIN OUTCOME MEASURES: Historical and clinical data on each infant in addition to laboratory data that included a white blood cell count, urinalysis, and blood, urine, and cerebrospinal fluid cultures. RESULTS: Two or more laboratory tests (not including chest radiographs) were obtained in 48% of all infants and 78% of febrile infants. Of the 91 infants with a history of a temperature of 38.0 degrees C or more or temperature on presentation of 38.0 degrees C or more, white blood cell counts were obtained in 77%, blood cultures in 75%, urinalyses in 53%, urine cultures in 60%, and analyses-cultures of cerebrospinal fluid in 47%. Febrile infants were 10 times more likely to get at least 2 laboratory tests than afebrile infants (P<.01). All 6 studies were done in 42 (58%) of 72 febrile infants compared with 7 (16%) of 43 afebrile infants (P<.001). Multiple logistic regression analysis identified a history of a temperature of 38.0 degrees C or more or temperature on presentation of 38.0 degrees C or more (odds ratio [OR] 10.0; 95% confidence interval [CI], 4.8%-21.0%; P<.001), oxygen saturation less than 92% on presentation (OR, 4.7; 95% CI, 1.9%-12.1%; P<.01), and history of apnea (OR, 0.1; 95% CI, 0.02-0.35; P<.001) as significant clinical predictors of whether laboratory studies were obtained. History of preterm gestation, aged younger than 28 days, previous antibiotic use, and presence of otitis media were not associated with obtainment of laboratory studies. No cases of bacteremia, urinary tract infection, or meningitis were found among all infants with bronchiolitis who had blood, urine, and/or cerebrospinal fluid cultures. CONCLUSION: There is wide variability in the diagnostic testing of infants aged 90 days or younger with bronchiolitis. The risks of bacteremia, urinary tract infection, and meningitis in infants with bronchiolitis seems to be low. History or a documented temperature of 38.0 degrees C or more; oxygen saturation of less than 92%, and history of apnea were associated with laboratory testing for bacterial infections.

Bacterial Infections↗
PubMed1999

Development of optimal techniques for cryopreservation of human platelets. I. Platelet activation during cold storage (at 22 and 8 degrees C) and cryopreservation.

Using the current blood bank storage conditions at 22 degrees C, the viability and function of human platelets can be maintained for only 5 days. This does not allow for the necessary and extensive banking of platelets needed to treat patients afflicted with thrombocytopenia, a side effect of many invasive surgeries such as cardiopulmonary bypass or bone marrow transplantation. The development of optimal techniques for long-term cryopreservation and banking of human platelets would provide the ability to greatly extend the viable life of the platelet and would fulfill an increasing and urgent need in many clinical applications. To determine the optimal techniques for platelet preservation, the expression of an activation marker, phosphatidylserine, on the platelet membrane during storage at 22 and 8 degrees C as well as during the different freezing preservation processes was examined using flow cytometry and annexin V binding assay. Human platelets were identified by both CD41 and light scatter in flow cytometry. In cryopreservation experiments, effects of the following factors on platelet activation were evaluated: (a) cryoprotective agents (CPAs) type: dimethyl sulfoxide (Me2SO), ethylene glycol (EG), and propylene glycol (PG), (b) CPA concentration ranging from 0 to 3 M, and (c) ending temperatures of a slow cooling process at -1 degrees C/min. Our results demonstrated that (a) approximately 50% of platelets were activated on days 7 and 16 at 22 and 8 degrees C, respectively; (b) platelets were not significantly activated after 30-min exposure to 1 M Me2SO, EG, and PG at 22 degrees C, respectively, and (c) there was a significant difference in cryoprotective efficacy among these three CPAs in preventing platelets from cryoinjury. After being cooled to -10 degrees C, 74% of the cryopreserved platelets survived (nonactivated) in 1 M Me2SO solution, while in 1 M EG and 1 M PG solutions, 62 and 42% of the platelets survived, respectively. Using the information that Me2SO consistently yields higher percentages of nonactivated platelets and does not seem to be cytotoxic to platelets for 30-min exposure time, this was found to be the optimal cryoprotective agent for platelets. In addition, significant Me2SO toxicity to platelets was not noted until Me2SO concentrations exceeded 2 M. Finally, a concentration of 1 M Me2SO proved to be the most effective at all cryopreservation ending temperatures tested (-10, -30, -60, and -196 degrees C). In conclusion, under the present experimental conditions, a storage temperature of 8 degrees C appeared to be much better than 22 degrees C. Although the potential chemical toxicity of 1 M Me2SO, EG, or PG is negligible, 1 M Me2SO was found to be optimum for cryopreservation of human platelets. PG has the least cryoprotective function for low-temperature platelet survival.

Blood Platelets↗