Satisfaction with nurse specialists in breast care clinics. Nurse led clinics may actually cost more.
Explore the source record for details and available documents.
Biopsy, Needle↗
Biomedical subjects
D Mitchell
Publications and source records attributed to D Mitchell.
A juxtacrine mechanism for neutrophil adhesion on platelets involves platelet-activating factor and a selectin-dependent activation process.
The aim of this study was to identify the molecular mechanisms involved in neutrophil adhesion to immobilized platelets with particular focus on the possible existence of a juxtacrine system for neutrophil-platelet interactions. Platelets were immobilized onto collagen (type I)-coated coverslips that were placed in a flow chamber and neutrophils were perfused across these confluent monolayers at a shear stress of 1 to 4 dynes/cm2. Neutrophils rolled, and a significant proportion (25% to 50%) adhered to platelet monolayers. P-selectin was expressed in very large quantities on the surface of platelets and mediated all of the rolling, whereas the beta2-integrin mediated firm adhesion. An activation mechanism for adhesion was necessary inasmuch as fixed neutrophils continued to roll on immobilized platelets, but did not adhere. Platelets adherent to collagen produced significant levels of platelet-activating factor (PAF). Accordingly, the firm adhesion of neutrophils to platelets was significantly inhibited by a PAF receptor antagonist (WEB 2086). Treatment of only the platelets with acetylhydrolase, which converts membrane-associated PAF to lyso-PAF, prevented 60% of the adhesion. These data suggest that PAF, on the surface of platelets, mediated a significant portion of the adhesive interaction. Addition of some selectin-binding carbohydrates (fucoidan or soluble SLEx analogs but not dextran sulfate) to the platelets caused rolling neutrophils to immediately adhere, an event that was not observed on histamine or thrombin-treated endothelium or P-selectin transfectants. These data support the view that a juxtacrine activation process exists on immobilized platelets for neutrophils. This process can be greatly enhanced on platelets and may involve a signaling mechanism through P-selectin.
Anticoagulants↗
Magnetic Field and Plasma Observations at Mars: Initial Results of the Mars Global Surveyor Mission
The magnetometer and electron reflectometer investigation (MAG/ER) on the Mars Global Surveyor spacecraft has obtained magnetic field and plasma observations throughout the near-Mars environment, from beyond the influence of Mars to just above the surface (at an altitude of approximately 100 kilometers). The solar wind interaction with Mars is in many ways similar to that at Venus and at an active comet, that is, primarily an ionospheric-atmospheric interaction. No significant planetary magnetic field of global scale has been detected to date (<2 x 10(21) Gauss-cubic centimeter), but here the discovery of multiple magnetic anomalies of small spatial scale in the crust of Mars is reported.
Journal Article↗
Mechanism of inhibition of electron transfer by amino acid replacement K362M in a proton channel of Rhodobacter sphaeroides cytochrome c oxidase.
The three-dimensional structure of cytochrome coxidase (COX) reveals two potential input proton channels connecting the redox core of the enzyme with the negatively charged (N-) aqueous phase. These are denoted as the K-channel (for the highly conserved lysine residue, K362 in Rhodobacter sphaeroides COX) and the D-channel (for the highly conserved aspartate gating the channel at the N-side, D132 in R. sphaeroides). In this paper, it is shown that the K362M mutant form of COX from R. sphaeroides, although unable to turnover with dioxygen as electron acceptor, can utilize hydrogen peroxide as an electron acceptor, with either cytochrome c or ferrocyanide as electron donors, with turnover that is close to that of the wild-type enzyme. The peroxidase activity is similar to that of the wild-type oxidase and is coupled to the generation of a membrane potential and to proton pumping. In contrast, no peroxidase activity is revealed in the D-channel mutants of COX, D132N, and E286Q. Reduction by dithionite of heme a3 in the fully oxidized oxidase is severely inhibited in the K362M mutant, but not in the D132N mutant. Apparently, mutations in the D-channel arrest COX turnover by inhibiting proton uptake associated with the proton-pumping peroxidase phase of the COX catalytic cycle. In contrast, the K-channel appears to be dispensable for the peroxidase phase of the catalytic cycle, but is required for the initial reduction of the heme-copper binuclear center in the first half of the catalytic cycle.
Amino Acid Substitution↗
Spontaneous movements during sleep in children: temporal organization and changes with age.
Developmental changes in the temporal organization of spontaneous movements during sleep was studied in children between 9 months and 11 years of age. Subjects were monitored in the home environment for the entire sleep period using actigraphy and videography. Rhythmicity in sleep-related spontaneous movements was examined using FFT and chi-square periodogram time series analyses. A dominant periodicity of 60-120 minutes was identified which was found to progressively lengthen with age. A microanalysis of the temporal structure of movements revealed a developmental decline in bout duration, but a paradoxical increase in bout frequency. These results show that motor activity becomes less robust and more fragmented as development progresses while retaining underlying rhythmic integrity, and argue for the dynamic influence of CNS maturation on the organization and expression of sleep-related spontaneous movements.
Age Factors↗
Purposeful activity for people with enduring mental health problems: reflections from a case study.
The desire to work is deeply rooted in the human psyche and involves both intrinsic and extrinsic factors. If this is indeed the case, then this form of human activity should be considered to be an important element of our lives and therefore worthy of intervention when circumstances restrict an individual's engagement with it. To investigate the therapeutic nature of work for people with enduring mental health problems, the author conducted a pilot case study of a work rehabilitation scheme in the United Kingdom. The main theme to emerge from the study was that of purposeful activity.
Goals↗
Promoting enjoyment and self-belief through work rehabilitation.
There has been a resurgence of interest in work rehabilitation in recent years. A variety of service models are in operation in a number of countries, all, to varying degrees, assisting mental-health clients achieve an optimum level of employment participation. However, little research has been conducted to examine how (and if) such schemes are structured to promote psycosocial rehabilitation. To explore such issues, the author carried out a pilot case study of a work-rehabilitation organization in Lincolnshire, United Kingdom. Two of the main themes, that emerged during the study, Hedonic Experiences and Self-Efficacy, are discussed in this article.
Health Promotion↗
Power, professions and evidence-based guidelines: lessons from an organizational case study.
AIM: This paper addresses the issues of evidence-based practice (EBP) in relation to power, professionalism and the British National Health Service reforms. BACKGROUND: There has been little discussion at organizational level over issues of professional boundaries, roles and tensions, which are inextricably linked with the drive for an evidence-based culture. METHODS: The paper is a reflection on the findings of a recent case study, which examined the management and organization of an independent sector provider of mental health services in its drive to address issues of EBP. FINDINGS: New managerial hegemony had altered the balance of power within the organization, there was an extension of managerial surveillance, competing political relationships and a general decline in medical dominance. CONCLUSION: Organizations should avoid 'personalizing' the debate on establishing a research-based culture. EBP requires structures to support it and groups representing the health care professions within the organization should be involved in identifying and making recommendations on EBP issues.
Evidence-Based Medicine↗
Different nocturnal body temperatures and sleep with forced-air warming in men and in women taking hormonal contraceptives.
We studied how forced-air warming, conventionally used to control body temperature during and after anaesthesia, affected the nocturnal rectal temperatures and sleep composition of young men and women. Seven healthy women who were taking oral or injection contraceptives, and six healthy men spent 3 nights in a controlled environment: an adaptation night followed by 2 nights when they slept under either a down duvet (baseline) or a quilt perfused with warm air (hot). Repeated analysis of variance (ANOVA) revealed significant gender differences in the body temperature responses. On the baseline night, despite sleeping under the same conditions, the women did not show a nocturnal drop in body temperature as shown by the men. Forced-air warming increased body temperature to a similar extent in the men and the women, and resulted in enhanced hyperthermia in the women, and blunted the drop in body temperature in the men, compared to their baseline nights. The significant increases in body temperature had no consequences, however, for the subjective sleep quality of either the men or women, and only minor consequences for objective sleep composition. Both men and women had increased amounts of Stage 2 sleep on the hot night (P < 0.04). In addition, the women had reduced rapid eye movement (REM) sleep when compared to their baseline night (P < 0.04). Our results confirm that in a passive thermal environment, women who are taking oral or injection contraceptives have higher nocturnal body temperatures than men. Also, as sleep architecture was minimally affected by the increases in body temperature of between 0.2 and 0.3 degree C on the hot night in the men and women, and subjective sleep quality was unaffected, our results question the existence of a tight association between sleep and body temperature.
Adult↗
The independent evolution of resistance to ciprofloxacin, rifampicin, and fusidic acid in methicillin-resistant Staphylococcus aureus in Australian teaching hospitals (1990-1995). Australian Group for Antimicrobial Resistance (AGAR).
Methicillin-resistant Staphylococcus aureus (MRSA) is endemic in teaching hospitals in eastern Australian states, with prevalence rates averaging 25-30% of all S. aureus. Between 1990 and 1995, 1467 non-duplicate MRSA isolates from clinically infected sites were tested in Sydney, Melbourne, and Brisbane as part of a national survey of staphylococcal susceptibility. We reviewed the differing evolution of resistance to ciprofloxacin, rifampicin, and fusidic acid. Despite similarities in community and hospital antibiotic use and MRSA prevalence rates, trends in resistance to the oral antibiotics in these cities have progressed independently of each other. In the 1995 survey in individual hospitals in Melbourne, 16-24% of strains were ciprofloxacin-resistant, compared with 80-100% in Sydney and 30-44% in Brisbane. There was great diversity of phage type patterns for ciprofloxacin-resistant strains, suggesting heterogeneous development of resistance. Rifampicin resistance was more closely associated with distinct dominant epidemic phage types, common to institutions in the same city, but without spread to the other cites. Between 1990 and 1995, these comprised 30-60% of all MRSA in Brisbane, compared with 5-10% in Melbourne and < 25% in Sydney. Fusidic acid resistance was uncommon and sporadic (< 5%), and was distributed equally between methicillin-resistant and methicillin-susceptible strains. Resistance to the oral agents in MRSA is due to a complex mix of antibiotic selection pressures and cross-infection with local and epidemic strains in closely related institutions. Each of these mechanisms can predominate, dependent on local factors and the antibiotics used.
Anti-Bacterial Agents↗
Chronic cough in the Holmes-Adie syndrome: association in five cases with autonomic dysfunction.
The Holmes-Adie syndrome consists of unilateral or bilateral tonic pupils with near light dissociation and tendon areflexia. It is associated with autonomic disturbances affecting sudomotor and vasomotor function. Five such patients are reported on who also had a troublesome chronic dry cough, which was of unknown aetiology and was resistant to a range of treatments. The cough may be related to involvement of afferent or efferent pathways in the vagus. Chronic cough may be an accompaniment in the Holmes-Adie syndrome, like other forms of autonomic dysfunction.
Adie Syndrome↗
Brain and abdominal temperatures at fatigue in rats exercising in the heat.
We measured brain and abdominal temperatures in eight male Sprague-Dawley rats (350-450 g) exercising voluntarily to a point of fatigue in two hot environments. Rats exercised, at the same time of the day, in three different trials, in random order: rest 23 degrees C, exercise 33 degrees C; rest 23 degrees C, exercise 38 degrees C; and rest 38 degrees C, exercise 38 degrees C. Running time to fatigue was 29.4 +/- 5.9 (SD), 22.1 +/- 3.7, and 14.3 +/- 2.9 min for the three trials, respectively. Abdominal temperatures, measured with intraperitoneal radiotelemeters, at fatigue in the three trials (39.9 +/- 0.3, 39.9 +/- 0.3, and 39.8 +/- 0.3 degrees C, respectively) were not significantly different from each other. Corresponding brain temperatures, measured with thermocouples in the hypothalamic region (40.2 +/- 0.4, 40.2 +/- 0.4, and 40.1 +/- 0.4 degrees C), also did not differ. Our results are consistent with the concept that there is a critical level of body temperature beyond which animals will not continue to exercise voluntarily in the heat. Also, in our study, brain temperature was higher than abdominal temperature throughout exercise; that is, selective brain cooling did not occur when body temperature was below the level limiting exercise.
Abdomen↗
Depletion of EBV-infected cells in donor marrow by counterflow elutriation.
Epstein-Barr virus (EBV)-associated posttransplantation lymphoproliferative disease (PTLD) is a well-recognized complication of T cell-depleted (TCD) allogeneic bone marrow transplantation (BMT). Certain methods of TCD, such as counterflow elutriation (CE), have not been associated with an increased incidence of PTLD. Since CE depletes B cells as well as T cells, the hypothesis that CE depletes donor marrow of EBV-infected cells was tested in this study. Marrow samples from 70 donors were assayed by qualitative and semi-quantitative polymerase chain reaction (PCR) amplification to detect EBV DNA in four cellular fractions produced by elutriation: a small cell fraction (F70), two intermediate-sized cell fractions (F110 and F140), and a large cell (hematopoietic precursor-enriched, lymphocyte-depleted) rotor-off (R/O) fraction. The distribution of B cells in elutriation fractions was 21% (F70), 59% (F110), 18% (F140), and 2% (R/O). Qualitatively, the frequency of EBV DNA detected in fractions was 49% (F70), 57% (F110), 73% (F140), and 44% (R/O). The relative concentration of EBV DNA in each fraction was determined by semiquantitative PCR. The mean number of EBV DNA copies per 150,000 cells was 0.57 (F70), 4.6 (F110), 5.7 (F140), and 0.61 (R/O). Relative EBV DNA load in each fraction was calculated by multiplying the mean concentration of EBV DNA per fraction and mean mononuclear cell content in each fraction. The relative distribution of EBV DNA was 0.5, 58, 40, and 1.5% in the F70, F110, F140, and R/O fractions, respectively. No correlation between the amount of EBV in the graft and development of PTLD could be made, because only one of the 70 recipients developed PTLD and this was following autologous hematopoietic recovery. Although these results demonstrate that the majority of EBV-infected cells in marrow are separated from the TCD graft by counterflow elutriation, further studies are required to differentiate the role of this phenomenon from that of other potential factors, such as the amount of T cell depletion and recovery of EBV immunity in the pathogenesis of PTLD after BMT.
Bone Marrow Cells↗
What you need to learn as a clinical director.
With the anticipated roll out of the main implications of the Government's white paper and the hoped for improvements in health care, it is a good time to review new roles for clinical directors in secondary and tertiary care trusts. This will inevitably mean changes in training needs for clinical directors who will face new demands and challenges as the complexity of life for them increases.
Education, Medical, Continuing↗
The roles of the two proton input channels in cytochrome c oxidase from Rhodobacter sphaeroides probed by the effects of site-directed mutations on time-resolved electrogenic intraprotein proton transfer.
The crystal structures of cytochrome c oxidase from both bovine and Paracoccus denitrificans reveal two putative proton input channels that connect the heme-copper center, where dioxygen is reduced, to the internal aqueous phase. In this work we have examined the role of these two channels, looking at the effects of site-directed mutations of residues observed in each of the channels of the cytochrome c oxidase from Rhodobacter sphaeroides. A photoelectric technique was used to monitor the time-resolved electrogenic proton transfer steps associated with the photo-induced reduction of the ferryl-oxo form of heme a3 (Fe4+ = O2-) to the oxidized form (Fe3+OH-). This redox step requires the delivery of a "chemical" H+ to protonate the reduced oxygen atom and is also coupled to proton pumping. It is found that mutations in the K channel (K362M and T359A) have virtually no effect on the ferryl-oxo-to-oxidized (F-to-Ox) transition, although steady-state turnover is severely limited. In contrast, electrogenic proton transfer at this step is strongly suppressed by mutations in the D channel. The results strongly suggest that the functional roles of the two channels are not the separate delivery of chemical or pumped protons, as proposed recently [Iwata, S., Ostermeier, C., Ludwig, B. & Michel, H. (1995) Nature (London) 376, 660-669]. The D channel is likely to be involved in the uptake of both "chemical" and "pumped" protons in the F-to-Ox transition, whereas the K channel is probably idle at this partial reaction and is likely to be used for loading the enzyme with protons at some earlier steps of the catalytic cycle. This conclusion agrees with different redox states of heme a3 in the K362M and E286Q mutants under aerobic steady-state turnover conditions.
Animals↗
Solar UVB-induced DNA damage and photoenzymatic DNA repair in antarctic zooplankton.
The detrimental effects of elevated intensities of mid-UV radiation (UVB), a result of stratospheric ozone depletion during the austral spring, on the primary producers of the Antarctic marine ecosystem have been well documented. Here we report that natural populations of Antarctic zooplankton also sustain significant DNA damage [measured as cyclobutane pyrimidine dimers (CPDs)] during periods of increased UVB flux. This is the first direct evidence that increased solar UVB may result in damage to marine organisms other than primary producers in Antarctica. The extent of DNA damage in pelagic icefish eggs correlated with daily incident UVB irradiance, reflecting the difference between acquisition and repair of CPDs. Patterns of DNA damage in fish larvae did not correlate with daily UVB flux, possibly due to different depth distributions and/or different capacities for DNA repair. Clearance of CPDs by Antarctic fish and krill was mediated primarily by the photoenzymatic repair system. Although repair rates were large for all species evaluated, they were apparently inadequate to prevent the transient accumulation of substantial CPD burdens. The capacity for DNA repair in Antarctic organisms was highest in those species whose early life history stages occupy the water column during periods of ozone depletion (austral spring) and lowest in fish species whose eggs and larvae are abundant during winter. Although the potential reduction in fitness of Antarctic zooplankton resulting from DNA damage is unknown, we suggest that increased solar UV may reduce recruitment and adversely affect trophic transfer of productivity by affecting heterotrophic species as well as primary producers.
Animals↗
Comparable effects of arteriolar and capillary stimuli on blood flow in rat skeletal muscle.
Although the capillary wall represents an active interface between blood and tissue, the potential role of the capillary in blood flow control has not been determined. The goals were (i) to establish the presence of the capillary sensing and communication phenomenon (Dietrich and Tyml, Microvasc. Res. 43, 87-99, 1992) in mammalian microvasculature and (ii) to determine the relative sensitivity of the capillary and the arteriole to locally applied vasoactive agents. Using intravital video microscopy, norepinephrine (NE; 10(-7)-3 x 10(-3) M), acetylcholine (ACh; 10(-4)-10(-2) M), or bradykinin (BK; 10(-9)-10(-3) M) was applied via micropipettes on capillaries (300 microm downstream from feeding arterioles) or on arterioles, at the surface of the extensor digitorum longus muscle of anesthetized rats. Red blood cell velocity (VRBC) in capillaries and arteriolar diameters was measured from video recordings. The overall control VRBC and control diameter were 190 microm/sec and 8.3 microm, respectively. NE applied on the capillary caused a dose-dependent reduction in VRBC (up to 100%, i.e., 0 microm/sec) via a constriction of the feeding arteriole. Both ACh and BK applied on the capillary caused a dose-dependent increase in VRBC (up to 115%) via arteriolar dilation. Based on two different approaches, these responses could not be explained in terms of diffusion of agents from capillary to the arteriole. When testing for the relative sensitivity of the arteriole and the capillary, application of NE and ACh on arterioles caused VRBC and diameter responses similar to those of capillary stimulations. When testing for the speed of response in these two microvessels, the time of noticeable VRBC change after NE (i.e., 10% from control) was also similar. We concluded that (i) the rat skeletal muscle capillary could respond to a variety of locally applied materials and (ii) the capillary could have as profound an effect on microvascular flow as the arteriole. Thus capillary could have the potential to participate in microvascular flow control.
Acetylcholine↗
Activity, blood temperature and brain temperature of free-ranging springbok.
We used miniature data loggers to record temperature and activity in free-ranging springbok (Antidorcas marsupialis) naturally exposed to severe nocturnal cold and moderate diurnal heat. The animals were active throughout the day and night, with short rests; the intensity of activity increased during daylight. Arterial blood temperature, averaged over many days, exhibited a circadian rhythm with amplitude < 1 degree C, but with a wide range which resulted from sporadic rapid deviations of body temperature. Peak blood temperature occurred after sunset. Environmental thermal loads had no detectable effect on blood temperature, even though globe temperature varied by > 10 degrees from day to day and > 20 degrees C within a day. Brain temperature increased approximately linearly with blood temperature but with a slope < 1, so that selective brain cooling tended to be activated at high body temperature, but without a precise threshold for the onset of brain cooling. Low activity attenuated selective brain cooling and high activity abolished it, even at high brain temperature. Our results support the concept that selective brain cooling serves to modulate thermoregulation rather than to protect the brain against heat injury.
Animals↗