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Biomedical subjects

D Knight

Publications and source records attributed to D Knight.

At least 37 records · Page 2Linked to original sources
PubMed2000

Use of resources, quality of life, and clinical outcomes in patients with and without new Q waves after thrombolytic therapy for acute myocardial infarction (from the GUSTO-I trial).

Previous reports indicate that patients who do not develop Q waves after thrombolytic therapy are a different population with a better long-term survival than those who do develop Q waves. However, the use of resources, quality of life, and health status of this population have not been fully evaluated. Using data from the Economics and Quality of Life subset of the Global Utilization of Streptokinase and tPA for Occluded Arteries study, we examined 30-day and 1-year mortality, use of resources, and quality-of-life measures among 1,830 of 3,000 patients with acute myocardial infarction and ST-segment elevation treated with thrombolytic therapy. At hospital discharge, 555 patients (30.2%) had not developed Q waves. These patients had lower mortality than patients with Q waves at 30 days (1.6% vs 4.5%, p <0.01) and at 1 year (4.7% vs 6.8%, p <0.04). Recurrent chest pain and dyspnea were similar at 30 days and 1 year. Patients without Q waves had significantly more angiography and trends toward higher readmission, revascularization, and use of calcium antagonists at 30 days. Angiography, revascularization, readmission, and quality of life were equivalent from 30 days to 1 year, with no sign of late instability. Logistic regression analysis showed an association between in-hospital revascularization and better survival and quality of life at 1 year. Conversely, there was no association between in-hospital use of calcium antagonists and outcome to explain the lower mortality in non-Q-wave patients. The absence of Q waves after thrombolytic therapy is a marker of success, implying better prognosis and equivalent quality of life, use of resources, and health status than for patients with Q-wave acute myocardial infarction and no sign of long-term unstable clinical course.

Aged↗
PubMed2000

Sorting of the vasopressin prohormone into the regulated secretory pathway.

The sorting of soluble proteins into the regulated secretory pathway (RSP) involves aggregation, but whether an additional sorting domain is also required is not clear. By fusing vasopressin prohormone (proVP) fragments to green fluorescent protein (eGFP) we have determined whether a sorting domain can function independently of the aggregative neurophysin domain. Although eGFP itself can be immunolocalised in the RSP of Neuro2A and AtT20 cells, most of the protein enters the constitutive pathway, and is found in the culture medium. In contrast, the N-terminal 27 residues of proVP promote residence in the RSP. Furthermore, only the processed form of this fusion was secreted when stimulated. We suggest a sorting mechanism based on the recognition of a sorting motif, the efficiency of which is enhanced by neurophysin aggregation.

Animals↗
PubMed2000

X-ray diffraction on spider silk during controlled extrusion under a synchrotron radiation X-ray beam.

The structure of a single thread of Nephila edulis silk has been studied by in situ X-ray diffraction from a living spider. A systematic increase of orientational order with increasing silking speed up to 40 mm s-1 was observed. Within a few mm from the spinnerets exit, crystalline domains with a beta-poly(L-alanine) structure were observed. The data also suggest an increase in crystalline fraction in the immediate vicinity of the spigot exit.

Algorithms↗
PubMed1999

Reply

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Journal Article↗
PubMed1999

Quality of life after emergency abdominal aortic aneurysm repair.

BACKGROUND: Quality of life issues following surgical procedures, especially those with high mortality, should be of prime importance. There have been few studies on the quality of life of patients following emergency abdominal aortic aneurysm repairs. The decision to continue to offer surgery to these patients, especially with present monetary constraints, should rely heavily on quality of life issues. Audits of major surgical procedures should be undertaken and quality of life included. METHODS: All patients in the Hawkes Bay area who had undergone emergency abdominal aortic aneurysm repairs since 1981 were identified and their quality of life assessed by means of the short form-36 (SF-36) questionnaire. RESULTS: One hundred and fifteen patients were identified as having had an abdominal aortic aneurysm repaired as an emergency. Sixty patients died peri-operatively and 19 subsequently. There were 28 patients available to complete the questionnaire, of whom 75% rated their global quality of life as good to excellent. Using the SF-36 questionnaire, there was no statistically significant difference between those patients who had undergone surgery (whether proven leak or not) and the age-matched healthy population. CONCLUSIONS: Quality of life remains good to excellent in the majority of patients following emergency abdominal aortic aneurysm repairs. This may help justify surgery being offered to patients with this condition. Quality of life should be considered as an important outcome rather than mortality only.

Aged↗
PubMed1999

Murder-suicides involving children: a 29-year study.

Review was undertaken from February 1969 to January 1998 at the State forensic science center (Forensic Science) in Adelaide, South Australia, of all cases of murder-suicide involving children <16 years of age. A total of 13 separate cases were identified involving 30 victims, all of whom were related to the perpetrators. There were 7 male and 6 female perpetrators (age range, 23-41 years; average, 31 years) consisting of 6 mothers, 6 father/husbands, and 1 uncle/son-in-law. The 30 victims consisted of 11 daughters, 11 sons, 1 niece, 1 mother-in-law, and 6 wives of the assailants. The 23 children were aged from 10 months to 15 years (average, 6.0 years). The 6 mothers murdered 9 children and no spouses, with 3 child survivors. The 6 fathers murdered 13 children and 6 wives, with 1 child survivor. This study has demonstrated a higher percentage of female perpetrators than other studies of murder-suicide. The methods of homicide and suicide used were generally less violent among the female perpetrators compared with male perpetrators. Fathers killed not only their children but also their wives, whereas mothers murdered only their children. These results suggest differences between murder-suicides that involve children and adult-only cases, and between cases in which the mother rather than the father is the perpetrator.

Adolescent↗
PubMed1998

Audit of early experience with inhaled nitric oxide in New Zealand neonatal intensive care units.

AIMS: To audit the use of inhaled nitric oxide for the treatment of persistent pulmonary hypertension of the newborn in New Zealand neonatal intensive care units. METHODS: Prospective data collection on all infants treated with inhaled nitric oxide in neonatal intensive care units in the 20-month period from first use to December 1995. Data included perinatal factors, principal diagnosis, echocardiogram results, ventilation details and response to nitric oxide, adverse reactions and outcome. RESULTS: Twenty-eight infants received nitric oxide in three centres, all bar one being 36 weeks or more gestation. Overall survival was 68%. Thirteen infants (46%) responded to nitric oxide treatment, 12 (92%) surviving. Seven (47%) of non-responders survived. Infants with primary pulmonary hypertension or meconium aspiration syndrome had 90% survival and more often responded to nitric oxide than infants with congenital diaphragmatic hernia (40% survival) or pulmonary hypoplasia (no survivors). No serious complications of treatment were recorded. CONCLUSIONS: Inhalational nitric oxide was not universally successful treatment for pulmonary hypertension of the newborn but was likely to have been life-saving in a proportion of cases. Future studies may allow better case selection. Ongoing audit of this new treatment is warranted.

Administration, Inhalation↗
PubMed1998

Switching transgene expression in the brain using an adenoviral tetracycline-regulatable system.

We have developed a tetracycline-regulatable adenoviral transfection system that mediates efficient long-term transfer of genes into neuronal cells in vivo. This system allows gene expression to be switched on, then off, and back on again simply by administering or removing doxycycline from the animals' drinking water. This regulatable adenoviral vector system should be of value in behavioral studies and in vivo studies of neuronal gene function, and may further the development of effective gene therapy strategies in the brain.

Adenovirus E1 Proteins↗
PubMed1998

Emphasizing terminal care as district nursing work: a helpful strategy in a purchasing environment?

This paper describes how within a study on the experiences of district nurses since the introduction of general practitioner purchasing, participants were encouraged to describe and define the district nursing service. The identification of terminal care by district nurses and others as a significant and defining example of district nursing work is explored and the possible reasons for its emphasis over other aspects of patient care. The extent to which terminal care was used within contract and purchasing discussions to aid general practitioner understanding of district nursing work and achieve extra funding is described. The paper concludes by questioning the extent to which terminal care is a helpful and accurate representation of what district nursing work entails, and the implications there may be in emphasizing one aspect of care within a purchasing environment.

Community Health Nursing↗
PubMed1998

Management and outcome of popliteal artery aneurysms in a New Zealand provincial centre.

BACKGROUND: The experience of management of popliteal artery aneurysms (PAA) in a provincial centre is described. METHODS: Patients were identified from vascular audit, and case notes were reviewed retrospectively. RESULTS: There were 17 patients with 23 PAA over 12 years. All patients were male, with a mean age of 73 years. Other aneurysms were present in 77% of patients, 59% had bilateral PAA and 41% had an associated abdominal aortic aneurysm (AAA). Mean follow-up was 3 years, 3 months (range, 1 month - 7 years). There were 11 acute procedures, and 12 elective. Reconstruction with bypass and ligation of the aneurysm was performed in all elective and 9/11 acute procedures. Of the 21 bypass procedures, 17 used autologous vein, three used GoreTex, and 1 composite graft. There were two PAA that were not reconstructable. All the vein grafts remained patent during the time of follow-up, but two of the three GoreTex grafts failed. Successful reconstruction was achieved in 11/12 elective and 9/11 acute cases. All grafts in the acute group remained patent during the time of follow-up (mean, 3.5 years), in the elective group 11/12 grafts (91%) remained patent (mean follow-up, 2.5 years). CONCLUSIONS: An excellent outcome was achieved in both elective and acute procedures. Autologous vein grafts appear to give better results than synthetic grafts. Due to the high incidence of multiple aneurysms, screening for other aneurysms is suggested.

Aged↗
PubMed1998

Renal Na-Si cotransporter NaSi-1 is inhibited by heavy metals.

Heavy metal intoxication leads to a number of reabsorptive and secretory defects in renal transport systems. We have studied the effects of several heavy metals on the expression of the renal Na-Si cotransporter NaSi-1. NaSi-1 cRNA was injected into Xenopus oocytes, and Na-Si cotransport activity was measured in the presence of mercury, lead, cadmium, or chromium. Mercury strongly inhibited NaSi-1 transport irreversibly by reducing both maximal velocity (Vmax) and Michaelis constant (Km) for inorganic sulfate (Si). Lead inhibited NaSi-1 transport reversibly by decreasing Vmax but not Km for Si. Cadmium showed weak reversible inhibition of NaSi-1 transport by decreasing only NaSi-1 Vmax. Chromium strongly inhibited NaSi-1 cotransport reversibly by reducing Km for Si by sevenfold, most probably by binding to the Si site, due to the strong structural similarity between the CrO4(2-) and SO4(2-) substrates. In conclusion, this study presents an initial report demonstrating heavy metals inhibit renal brush border Na-Si cotransport via the NaSi-1 protein through various mechanisms and that this blockade may be responsible for sulfaturia following heavy metal intoxication.

Animals↗
PubMed1997

Adenosine A3 receptor stimulation inhibits migration of human eosinophils.

Activation of adenosine A3 receptors (A3-R) produced a dose-dependent reduction in the chemotaxis of human eosinophils to platelet-activating factor (PAF), RANTES, and leukotriene B4 (LTB4) to a maximum of 58, 48, and 52%, respectively (P < 0.02). This effect was completely reversed by selective A3-R antagonists. In contrast, activation of A1 or A2a-R did not affect PAF-induced eosinophil chemotaxis. PAF up-regulated the expression of CDllb/CD18, down-regulated L-selectin, and also increased F-actin assembly in eosinophils. The expression of these activation markers was not influenced by A3-R, A2a, or A1-R stimulation. Activation of A3-R may play an important role in inflammation by inhibiting eosinophil migration.

Adenosine↗
PubMed1997

Localization of leukaemia inhibitory factor to airway epithelium and its amplification of contractile responses to tachykinins.

1. In neural tissue, leukaemia inhibitory factor (LIF) is an important trophic cytokine. In this investigation, we determined if LIF was present in human and guinea-pig airways and examined the role of this cytokine in modulating airway responses to endogenous and exogenous tachykinins as well as muscarinic receptor and beta-adrenoceptor stimulation. 2. The presence of LIF in both human and guinea-pig airways was determined by immunohistochemistry. Guinea-pig tracheal explants were incubated in CRML-1066 media containing LIF (0.5, 5 or 50 ng ml-1) for periods of 3, 6, 24 and 48 h. Tracheal rings were then transferred to organ baths for measurement of isometric force in response to carbachol, capsaicin, the neurokinin1 (NK1) receptor agonist [Sar9,Met(O2)11]-substance P (SP), the NK2 receptor agonist neurokinin A (NKA) and isoprenaline. 3. LIF immunoreactivity was observed primarily in basally situated cells in the airway epithelium of both large and small airways. Less intense immunoreactivity was observed in vascular endothelium and glandular epithelium. 4. Treatment with LIF (0.5 ng ml-1) for 3 and 6 h significantly increased contractile responses to capsaicin by 42% and 43%, respectively, compared to time controls, whereas higher concentrations of LIF (5 and 50 ng ml-1) enhanced capsaicin-induced contractions only after 6 h. After 24 h, responses to capsaicin were not significantly different from 0 h control. Contractile responses to capsaicin following exposure to LIF at any concentration for 24 h were not significantly different from relative time control values. 5. Responses to [Sar9,Met(O2)11]-SP, carbachol and isoprenaline were not influenced by time in culture or by exposure to LIF for up to 48 h. Contractile responses induced by NKA were not influenced by 3 or 6 h exposure to LIF, but at 24 and 48 h the mean maximum contractile responses to NKA were significantly increased by 33% and 35%, respectively, compared to control. 6. These results demonstrate that LIF is present in guinea-pig and human airway epithelium, and modulates airway responses to tachykinins. In the acute setting LIF augments the capsaicin-induced release of endogenous tachykinins, whilst in the longer term (> 24 h), LIF increases airway smooth muscle responses to tachykinins via an NK2 receptor selective mechanism. We conclude that LIF may be an important effector molecule in the response of airways to injury or inflammation.

Animals↗
PubMed1996

Influence of angioscopic vein graft preparation on development of neointimal hyperplasia in an organ culture model of human saphenous vein.

PURPOSE: Angioscopy for in situ vein graft preparation has been criticized on the basis that the trauma of instrumentation may predispose to accelerated intimal hyperplasia, jeopardizing patency rates following infrainguinal revascularization. The aim of this study was to assess the effects of angioscopic preparation on endothelial integrity and smooth muscle cell (SMC) behavior in an established organ culture model of human saphenous vein (HSV). METHODS: HSV was harvested from 12 patients during bypass surgery before and after angioscopic preparation. Endothelial integrity was evaluated by immunohistochemical staining with JC-70 and scanning electron microscopy (SEM); remaining segments of pre- and postangioscopy vein were maintained in culture for 14 days in medium supplemented with 30% fetal calf serum. Viability was confirmed by measurement of tissue adenosine triphosphate on day 14 and thickness of the neointima was measured by computerized image analysis of histologic sections. Monoclonal antibodies to proliferating cell nuclear antigen (PCNA) were used as an immunohistochemical marker for proliferating SMCs. RESULTS: There was a significant reduction in the percentage staining by JC-70 (71.3% versus 20.4%) in pre- versus postangioscopy vein (p = 0.002 by Wilcoxon's rank test; n = 12). This was supported by SEM images. Despite this, there were no significant differences between the pre- and postangioscopy HSVs after 14 days of culture with respect to neointimal thickness (61 versus 56 microns) and staining with PCNA (4.80 versus 4.08 nuclei per 10 microns), all according to Wilcoxon's rank test. CONCLUSIONS: Angioscopic vein graft preparation is associated with endothelial cell loss but does not induce additional neointimal hyperplasia in HSV in vitro. These results suggest that angioscopic manipulation does not alter SMC behavior.

Adenosine Triphosphate↗
PubMed1996

Science and culture in mid-Victorian Britain: the reviews, and William Crookes' Quarterly Journal of Science.

Charles Darwin's Origin of Species was published in 1859, and we are often disposed to see it as marking an epoch in the struggle between religion and science. Recent analyses especially of the part played by T. H. Huxley, 'Darwin's bulldog', emphasise instead (or as well) Huxley's aim to exclude affable 'gentlemen of science' from what was becoming a profession for experts. Evidence from the Reviews of the period show that science accounted for some 10% of the articles; but also that demand for this very general literature was falling, as science and humanities indeed grew apart into what C.P. Snow later called 'two cultures'.

History, 19th Century↗
PubMed1996

General practitioners and clinical guidelines: a survey of knowledge, use and beliefs.

BACKGROUND: Clinical practice guidelines are being developed for a variety of reasons. To date, there has been little investigation of the perspectives of those who are recommended to use them. AIM: The survey reported here set out to investigate how familiar general practitioners are with a range of published guidelines, to assess whether they have used them, and to describe their attitudes to the guidelines and the methods of implementing them. METHOD: A postal questionnaire was sent to a random sample of 559 general practitioners in the North and Yorkshire region in March 1995. Questions were organized around the topics of: knowledge; use; practice change; beliefs; pressure felt to use the guidelines; and methods of implementation. Basic classificatory data on gender; year of qualification; partnership and fundholding status were also collected. RESULTS: Replies were received from 300 doctors (54%). Knowledge and use of the three selected guidelines varied, but was generally towards the 'high' end of the scale. Doctors showed a high degree of homogeneity in their attitudes to guidelines, which were generally positive. Only single-handed practitioners varied from this pattern of responses. Most of the pressure to use the guidelines was felt to come from the Department of Health, and the least pressure from patients. Doctors felt that the methods of implementation that involved them in educational events and discussion with colleagues were most likely to have an impact on them. CONCLUSION: General practitioners are receptive to guideline initiatives, and their views are in line with existing or proposed implementation strategies. More investigation of the concept of 'use' is needed.

Attitude of Health Personnel↗
PubMed1995

Lipopolysaccharide (LPS) neutralizing peptides reveal a lipid A binding site of LPS binding protein.

Endotoxic shock follows a cascade of events initiated by release of lipopolysaccharide during infection with Gram-negative organisms. Two overlapping 15-mer peptides were identified, corresponding to residues 91-108 of human lipopolysaccharide binding protein that specifically bound the lipid A moiety of lipopolysaccharide with high affinity. The peptides inhibited binding of lipopolysaccharide to lipopolysaccharide binding protein, inhibited the chromogenic Limulus amebocyte lysate reaction, and blocked release of tumor necrosis factor alpha following lipopolysaccharide challenge both in vitro and in vivo. These results suggest lipopolysaccharide binding protein residues 91-108 form at least part of the lipopolysaccharide binding site. Moreover, derivatives of lipopolysaccharide binding protein residues 91-108 might modulate lipopolysaccharide toxicity in the clinical setting.

Acute-Phase Proteins↗