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1.
Anaesthesia ; 75(3): 353-358, 2020 Mar.
Article in English | MEDLINE | ID: mdl-31828768

ABSTRACT

In our previous study, a Paediatric Early Warning Score could be calculated for only one-fifth of 102,993 children transported by ambulance to hospital, as components other than supplemental oxygen were not reliably measured: respiratory rate 90,358 (88%); Glasgow Coma Score 83,648 (81%); heart rate 83,330 (81%); time to capillary reperfusion 81,685 (79%); oxygen saturation 71,372 (69%); temperature 60,402 (59%); systolic blood pressure 37,088 (36%). We tested 12 abbreviated scores with 3-5 components. The discrimination of these 12 scores for the primary outcome (30-day mortality or admission to paediatric intensive care), as measured by the area under the receiving operator characteristic curve, ranged from 0.69 to 0.80. Scores could be calculated for at most 74,508 (72%) children when heart rate, conscious level and respiratory rate were measured, with or without supplemental oxygen: the discrimination of these two versions was 0.75 and 0.77, respectively. Optimal threshold scores of 3 and 2 for these two abbreviated versions discriminated an outcome rate of 2-3% in about one third of children from the other children who had < 1% rate of outcome.


Subject(s)
Early Warning Score , Emergency Medical Services/methods , Adolescent , Child , Child, Preschool , Consciousness Disorders/diagnosis , Critical Care , Female , Glasgow Coma Scale , Heart Rate , Humans , Infant , Male , Oxygen/therapeutic use , ROC Curve , Reproducibility of Results , Respiratory Rate , Scotland , Transportation of Patients , Treatment Outcome
2.
Resuscitation ; 133: 153-159, 2018 12.
Article in English | MEDLINE | ID: mdl-30336232

ABSTRACT

INTRODUCTION: Physiological deterioration often precedes clinical deterioration as patients develop critical illness. Use of a specific Paediatric Early Warning Score (PEWS), based on basic physiological measurements, may help identify children prior to their clinical deterioration. NHS Scotland has adopted a single national PEWS - PEWS (Scotland). We aim to look at the utility of PEWS (Scotland) in unselected paediatric ambulance patients. METHODS: We performed a retrospective cohort of all ambulance patients aged under 16 years conveyed to hospital in Scotland between 2011 and 2015. Patients were matched to their 30 day mortality and ICU admission using data linkage. RESULTS: Full results were available for 21,202 children and young people (CYP). On multivariate logistic regression, PEWS (Scotland) was an independent predictor of the primary outcome (ICU admission within 48 h or death within 30 days) with an odds ratio of 1.403 (95%CI 1.349-1.460, p < 0.001). Area Under Receiving Operator Curve (AUROC) for aggregated PEWS was 0.797 (95% CI 0.759 to 0.836, p < 0.001). The optimal PEWS using Youlden's Index was 5. DISCUSSION: These data show PEWS (Scotland) to be a useful tool in a pre-hospital setting. A single set of physiological observations undertaken prior to arrival at hospital can identify a group of children at higher risk of an adverse in-hospital outcome. Paediatric care is becoming more specialised and focussed on a smaller number of centres. In this context, use of PEWS (Scotland) in the pre-hospital phase may allow changes to paediatric pre-hospital pathways to improve both admission to ICU and child mortality rates.


Subject(s)
Clinical Deterioration , Emergency Medical Services/statistics & numerical data , Hospitalization/statistics & numerical data , Severity of Illness Index , Vital Signs , Adolescent , Child , Child, Preschool , Critical Illness/epidemiology , Female , Humans , Infant , Infant, Newborn , Logistic Models , Male , Predictive Value of Tests , ROC Curve , Retrospective Studies , Scotland/epidemiology
3.
Ann Oncol ; 26(10): 2085-91, 2015 Oct.
Article in English | MEDLINE | ID: mdl-26272806

ABSTRACT

BACKGROUND: This randomised, open-label, phase I/II study evaluated the efficacy and safety of nintedanib, an oral, triple angiokinase inhibitor, combined with chemotherapy, relative to bevacizumab plus chemotherapy as first-line therapy in patients with metastatic colorectal cancer (mCRC). PATIENTS AND METHODS: Patients with histologically confirmed mCRC (adenocarcinoma), an Eastern Cooperative Oncology Group performance status ≤ 2 and adequate organ function were included. Patients were randomised 2:1 to receive nintedanib 150 mg or 200 mg b.i.d. plus mFOLFOX6 (oxaliplatin 85 mg/m(2), l-leucovorin 200 mg/m(2) or d,l-leucovorin 400 mg/m(2), 5-fluoruracil bolus 400 mg/m(2) followed by 2400 mg/m(2), every 2 weeks) or bevacizumab (5 mg/kg every 2 weeks) plus mFOLFOX6. During phase I, patients underwent a 3 + 3 dose-escalation schema to determine the maximum tolerated dose (MTD) of nintedanib in combination with mFOLFOX6. The primary end point was progression-free survival (PFS) rate at 9 months. Objective response (OR) was a secondary end point. RESULTS: The nintedanib recommended phase II dose was 200 mg b.i.d. plus mFOLFOX6 based on safety data from phase I (n = 12). Of 128 patients randomised in the phase II part, 126 received treatment (nintedanib plus mFOLFOX6, n = 85; bevacizumab plus mFOLFOX6, n = 41). PFS at 9 months was 62.1% with nintedanib and 70.2% with bevacizumab [difference: -8.1% (95% confidence interval -27.8 to 11.5)]. Confirmed ORs were recorded in 63.5% and 56.1% of patients in the nintedanib and bevacizumab groups, respectively. The incidence of adverse events (AEs) considered related to treatment was 98.8% with nintedanib and 97.6% with bevacizumab; the incidence of serious AEs was 37.6% with nintedanib and 53.7% with bevacizumab. The pharmacokinetics of nintedanib and the components of mFOLFOX6 were unaffected by their combination. CONCLUSIONS: Nintedanib in combination with mFOLFOX6 showed efficacy as first-line therapy in patients with mCRC with a manageable safety profile and further studies in this population are warranted.


Subject(s)
Adenocarcinoma/drug therapy , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Colorectal Neoplasms/drug therapy , Adenocarcinoma/mortality , Adenocarcinoma/secondary , Adult , Aged , Aged, 80 and over , Bevacizumab/administration & dosage , Colorectal Neoplasms/mortality , Colorectal Neoplasms/pathology , Female , Fluorouracil/administration & dosage , Follow-Up Studies , Humans , Indoles/administration & dosage , Leucovorin/administration & dosage , Male , Middle Aged , Neoplasm Metastasis , Neoplasm Staging , Organoplatinum Compounds/administration & dosage , Oxaliplatin , Prognosis , Survival Rate
4.
J Thromb Haemost ; 7(2): 277-87, 2009 Feb.
Article in English | MEDLINE | ID: mdl-19054318

ABSTRACT

BACKGROUND: We assessed the relation between admission levels of activated factor XII type A (XIIaA), and long-term all-cause and cardiac mortality and recurrent troponin T (TnT) positive cardiovascular events in a consecutive cohort of 870 patients admitted with a clinically strongly suspected acute coronary syndrome (ACS). METHODS AND RESULTS: After a 24-month follow-up period, 138 patients (15.8%) had died and 155 (17.8%) had suffered from a recurrent TnT positive (TnT > 0.05 ng mL(-1)) event. XIIaA levels were significantly lower in long-term survivors than in patients who died (22.9 (17.7-32.1) vs. 27.2 (20.0-39.7) pmol L(-1) [median, 25 and 75% percentiles], P < 0.001). The unadjusted hazard ratio for death within 2 years in patients with XIIaA in the highest quartile was 2.49 (95% confidence interval (CI), 1.52-4.06) as compared with patients with XIIaA in the lowest quartile. In a stepwise Cox regression model for death within 2 years, XIIaA added prognostic information for all-cause mortality (HR 2.05; 95% CI, 1.21-3.47) above and beyond age, a history of heart failure, ST-segment elevation, TnT and B-type natriuretic peptide (BNP). In the subgroup of patients with an admission TnT < or = 0.05 ng mL(-1), XIIaA provided independent prognostic information for all-cause mortality (HR 3.88; 95% CI, 1.66-9.08) and for the combined endpoint of death or recurrent TnT positive event (HR 2.46; 95% CI, 1.34-4.50). CONCLUSION: XIIaA, a recently identified in vivo form of activated factor XII is an independent indicator of long-term all-cause mortality in patients admitted with chest pain, providing prognostic information above and beyond conventional risk factors.


Subject(s)
Chest Pain/mortality , Factor XIIa/analysis , Predictive Value of Tests , Aged , Female , Humans , Male , Middle Aged , Mortality , Prognosis , Proportional Hazards Models , Risk Factors , Survival Analysis , Survivors
5.
Gut ; 58(5): 668-78, 2009 May.
Article in English | MEDLINE | ID: mdl-19091821

ABSTRACT

OBJECTIVE: Unlike excisional haemorrhoidectomy, stapled anopexy (SA), which does not involve radical excision, has theoretical advantages, thus offering potential patient benefits. We compared the clinical efficacy, safety and patient acceptability of SA, with closed haemorrhoidectomy (CH). PATIENTS AND METHODS: 182 patients with symptomatic haemorrhoids (grades II, III, IV) were randomly assigned to receive SA or CH and were followed for up to 1 year (6, 12, 24, 48 weeks) after operation. Postoperative pain, symptom control, complications, re-treatment rates, patient satisfaction, and quality of life were compared on an intention-to-treat basis. RESULTS: Postoperative pain in the SA group (n = 91) was significantly lower (p = 0.004, Mann-Whitney U test). At 1 year there were no significant differences in the symptom load, symptom severity or the disease severity between the two groups. Overall complication rates were similar but faecal urgency was reported more frequently following SA (p = 0.093, Fisher's exact test). Despite a similar rate of residual symptoms, prolapse control was better with CH (p = 0.087, Fisher's exact test), and more patients in the SA group required re-treatment for residual prolapse at 1 year (p = 0.037, Fisher's exact test). However, more patients rated SA as an excellent operation at 6 and 12 weeks (p = 0.008 and 0.033, binary logistic regression) and were willing to undergo a repeat procedure if required (p = 0.018, Fisher's exact test). CONCLUSION: Stapled anopexy offers a significantly less painful alternative to excisional haemorrhoidectomy and achieves a higher patient acceptability. Although the overall symptom control and safety are similar in the majority of the patients, the re-treatment rate for recurrent prolapse at 1 year is higher following SA when compared to CH.


Subject(s)
Anal Canal/surgery , Diathermy/adverse effects , Hemorrhoids/surgery , Surgical Stapling/adverse effects , Digestive System Surgical Procedures/instrumentation , Female , Hemorrhoids/complications , Humans , Male , Middle Aged , Pain, Postoperative/etiology , Patient Satisfaction , Prospective Studies , Quality of Life , Suture Techniques , Treatment Outcome
6.
Ultrason Sonochem ; 15(3): 171-6, 2008 Mar.
Article in English | MEDLINE | ID: mdl-17482498

ABSTRACT

Our previous report based on a batch reactor system for the Advanced Fenton Process (AFP) showed that pH, hydrogen peroxide and the organic substances treated are among the most important factors affecting the oxidation efficiency. As an extended study towards its potential commercialisation, this paper reports the effects of the main process parameters including those relating to a new laboratory scale AFP flow-through system. In order to systemise and correlate the results, the Taguchi experimental design method was used. Total organic carbon (TOC) removal was utilised as the measure of the oxidation efficiency and it was found that the removal of phenol from aqueous solution at pH 2.0 and 2.5 was very similar but hydrogen peroxide supply significantly affected the TOC removal with the change of flow rate from 14.4 ml/h to 60 ml/h. Also, the initial concentration of phenol was a highly significant factor, with higher concentrations resulting in a lower TOC removal rate. The temperature effects in the range of 14-42 degrees C were investigated and it was found that there was accelerated oxidation of phenol in the early stages but after 90 min there was no significant difference between the results. Sonication with a bath type sonicator resulted in relatively small enhancements of TOC removal but further studies with cup-horn sonication showed that TOC removal increased with higher intensity of sonication.


Subject(s)
Iron/chemistry , Phenol/chemistry , Sonication , Ultrasonics , Carbon/chemistry , Chemistry, Organic/methods , Equipment Design , Hydrogen Peroxide/chemistry , Hydrogen-Ion Concentration , Models, Chemical , Oxygen/chemistry , Temperature , Time Factors
7.
Br Poult Sci ; 45(3): 400-3, 2004 Jun.
Article in English | MEDLINE | ID: mdl-15327127

ABSTRACT

1. Sample fertility and the median number of points of hydrolysis produced by spermatozoa in the perivitelline layer from the germinal disc area were determined in samples of 60 eggs taken weekly from each of two commercial broiler breeder flocks. 2. Flock fertility remained above 90% from weeks 30 to 45, after which it fell in both flocks, reaching 85% in Flock A by week 51 and 76% in Flock B by week 55. 3. Sample fertility, as assessed by the Kosin test, followed a similar trend, but showed more variation; the same was true for the proportion of eggs with at least one perivitelline hole. 4. In Flock A, the median number of perivitelline holes in samples increased from 145 in week 30 to reach a maximum of 323 on week 39, thereafter falling to 109 in week 51; for Flock B, the equivalent figures for weeks 30, 36 and 55 were 160, 266 and 29, respectively. A quadratic model confirmed that the weekly sample median perivitelline holes peaked at weeks 40 and 37 in Flocks A and B, respectively. 5. The results show that transfer of spermatozoa by males into females and subsequently into eggs begins to decline 8 (Flock A) to 9 (Flock B) weeks before it is noticeable as a significant reduction in flock fertility and that mating efficiency, unlike fertility, is never in apparent equilibrium, but rises to a peak before 40 weeks and then falls. 6. The pattern of sperm transfer suggests that the reduction in fertility of broiler flocks could well be for social or for physiological reasons other than those associated with 'ageing'.


Subject(s)
Breeding , Chickens/physiology , Fertility , Sperm-Ovum Interactions/physiology , Agriculture/methods , Animals , Female , Male , Time Factors
8.
Nurse Educ Today ; 23(3): 183-90, 2003 Apr.
Article in English | MEDLINE | ID: mdl-12672386

ABSTRACT

A previous qualitative study [Nurse Education Today 20 (2000) 499] investigated perceptions of nurse teachers, student nurses and preceptors of the theory-practice gap said to exist within nursing. One theme was views of how the theory-practice gap could be closed. A subsequent quantitative study is reported here, in which this theme was translated into three factors. A full factorial experimental design was used to study the effect of these factors on theoretical knowledge and practical skill acquisition in a sample of first year undergraduate student nurses from one institution of higher education (n=19). The effect of whether a nurse teacher or preceptor taught students theoretical elements relating to a clinical specialty, whether the nurse teacher and preceptor collaborated on the content of what was taught to students and whether students went straight to, or delayed the clinical specialty following theoretical input, was examined. The results demonstrated preceptors were more effective than nurse teachers in promoting theoretical knowledge relating to their clinical specialty. Collaboration between the preceptors and nurse teachers on teaching content was ineffective at increasing theoretical knowledge. Delay between theoretical input and clinical experience was not detrimental for medical placements and for rehabilitation placements, resulted in an improved theoretical knowledge.


Subject(s)
Clinical Competence , Interprofessional Relations , Nursing Theory , Preceptorship , Specialties, Nursing/education , Analysis of Variance , Education, Nursing/methods , Humans , United Kingdom
9.
Reprod Fertil Dev ; 14(7-8): 401-5, 2002.
Article in English | MEDLINE | ID: mdl-12617782

ABSTRACT

Semen quality in captive-bred Houbara bustards, Chlamydotis undulata undulata, was assessed during three consecutive breeding seasons. In any one season, sperm quality, in terms of the proportion of eosin-permeable spermatozoa and of spermatozoa with abnormally large nuclei, varied among individual males, but not among their ejaculates. Neither the proportion of spermatozoa with large nuclei, nor those permeable to eosin were related to the total sperm output of males. The fertilizing ability of males was related to their mean seasonal proportion of eosin-permeable spermatozoa, but not the proportion of spermatozoa with large nuclei. The ranking of males on the basis of the proportion of spermatozoa with large nuclei in their ejaculates was significantly positively correlated between seasons, although ranking on the basis of sperm eosin-permeability was not. The cause or consequence of producing spermatozoa with large nuclei (and excess DNA) remains to be elucidated, but appears to be a trait that is characteristic of houbara bustard males that is maintained between breeding seasons.


Subject(s)
Animals, Zoo , Birds , Semen/physiology , Animals , Breeding , Cell Nucleus/ultrastructure , Eosine Yellowish-(YS) , Male , Permeability , Seasons , Spermatozoa/physiology , Spermatozoa/ultrastructure
10.
FEBS Lett ; 500(1-2): 45-51, 2001 Jun 29.
Article in English | MEDLINE | ID: mdl-11434924

ABSTRACT

The properties of the malaria parasite-induced permeability pathways in the host red blood cell have been a major area of interest particularly in the context of whether the pathways are host- or parasite-derived. In the present study, the whole-cell configuration of the patch-clamp technique has been used to show that, compared with normal cells, chicken red blood cells infected by Plasmodium gallinaceum exhibited a 5-40-fold larger membrane conductance, which could be further increased up to 100-fold by raising intracellular Ca(2+) levels. The increased conductance was not due to pathways with novel electrophysiological properties. Rather, the parasite increased the activity of endogenous 24 pS stretch-activated non-selective cationic (NSC) and 62 pS calcium-activated NSC channels, and, in some cases, of endogenous 255 pS anionic channels.


Subject(s)
Erythrocytes/parasitology , Ion Channels/metabolism , Plasmodium gallinaceum/physiology , Animals , Chickens , Electrophysiology , Erythrocytes/metabolism , Erythrocytes/physiology , Host-Parasite Interactions , Ion Channels/physiology , Patch-Clamp Techniques
11.
Am J Physiol Cell Physiol ; 280(6): C1576-87, 2001 Jun.
Article in English | MEDLINE | ID: mdl-11350753

ABSTRACT

In human erythrocytes infected with the mature form of the malaria parasite Plasmodium falciparum, the cytosolic concentration of Na(+) is increased and that of K(+) is decreased. In this study, the membrane transport changes underlying this perturbation were investigated using a combination of (86)Rb(+), (43)K(+), and (22)Na(+) flux measurements and a semiquantitative hemolysis technique. From >15 h postinvasion, there appeared in the infected erythrocyte membrane new permeation pathways (NPP) that caused a significant increase in the basal ion permeability of the erythrocyte membrane and that were inhibited by furosemide (0.1 mM). The NPP showed the selectivity sequence Cs(+) > Rb(+) > K(+) > Na(+), with the K(+)-to-Na(+) permeability ratio estimated as 2.3. From 18 to 36 h postinvasion, the activity of the erythrocyte Na(+)/K(+) pump increased in response to increased cytosolic Na(+) (a consequence of the increased leakage of Na(+) via the NPP) but underwent a progressive decrease in the latter 12 h of the parasite's occupancy of the erythrocyte (36-48 h postinvasion). Incorporation of the measured ion transport rates into a mathematical model of the human erythrocyte indicates that the induction of the NPP, together with the impairment of the Na(+)/K(+) pump, accounts for the altered Na(+) and K(+) levels in the host cell cytosol, as well as predicting an initial decrease, followed by a lytic increase in the volume of the host erythrocyte.


Subject(s)
Erythrocyte Membrane/enzymology , Erythrocyte Membrane/parasitology , Malaria/metabolism , Plasmodium falciparum , Sodium-Potassium-Exchanging ATPase/metabolism , Animals , Biological Transport/physiology , Cytosol/enzymology , Humans , Models, Biological , Potassium/metabolism , Potassium Radioisotopes/pharmacokinetics , Rubidium Radioisotopes/pharmacokinetics , Sodium/metabolism , Sodium Radioisotopes/pharmacokinetics
12.
Cryo Letters ; 22(4): 255-62, 2001.
Article in English | MEDLINE | ID: mdl-11788866

ABSTRACT

A biometric approach partly involving principal component analysis has been used to examine the changes in phenotypic characters of shoot-tip derived potato plants recovered from tissue culture, dimethyl sulphoxide (DMSO) and cryopreservation in comparison with field-grown tuber-derived plants. There were significant differences in the quantitative characters height and tuber weight in the cryopreserved plants compared to those derived from DMSO treatment and tissue culture. These three experimental groups were shown to significantly differ from field-grown plants in the characters, tuber weight followed by height and length of petiole. The use of biometrics as an analytical approach in genetic stability assessments of plants recovered from cryopreservation to relatively small sample sizes is discussed.


Subject(s)
Cryopreservation , Cryoprotective Agents/pharmacology , Culture Techniques , Dimethyl Sulfoxide/pharmacology , Plant Shoots , Solanum tuberosum/anatomy & histology , Biometry , Phenotype , Solanum tuberosum/growth & development
13.
Br Poult Sci ; 41(4): 395-400, 2000 Sep.
Article in English | MEDLINE | ID: mdl-11128379

ABSTRACT

1. The frequency distribution of points of hydrolysis produced by spermatozoa in the perivitelline layer from directly over the germinal disc was examined in 60 samples of 60 eggs from commercial broiler breeder flocks. 2. Typically, these distributions were positively skewed, although log transformation of the data revealed 2 populations: one representing eggs which contained no evidence of spermatozoa and another in which the data were, generally, normally distributed. 3. Problem flocks with low fertility had more eggs without evidence of spermatozoa and, compared to control flocks with acceptable fertility, a lower median and mean before and after log transformation, respectively. 4. In 4 flocks studied between 30 to 55 weeks of age, the median number of points-of-hydrolysis in samples of eggs fell from around 200 at peak to less that 20 at 55 weeks, whilst the mean proportion of fertile eggs laid by the whole flocks fell from 94% at peak to around 79% at 55 weeks. 5. A log-linear relationship was demonstrated between flock fertility and the median points-of-hydrolysis from the inner perivitelline layer over the germinal disc in samples of 60 eggs (R2=0.79). 6. The main advantages of this system for measuring sperm-in-eggs are that it is technically simple and presents a more expanded scale than fertility, so that an estimation of whole flock fertility can be derived from a sample of 60 eggs.


Subject(s)
Chickens/physiology , Reproduction/physiology , Sperm-Ovum Interactions/physiology , Age Factors , Animals , Female , Male , Ovum/physiology , Spermatozoa/physiology , Statistics, Nonparametric , Vitelline Membrane/physiology
14.
J Adv Nurs ; 31(5): 1216-27, 2000 May.
Article in English | MEDLINE | ID: mdl-10840256

ABSTRACT

'You feel helpless, that's exactly it': parents' and young people's control beliefs about bed-wetting and the implications for practice Young people wet the bed when they fail to wake up to a full bladder. The causes of bed-wetting are far from certain and this uncertainty is reflected in the diversity of treatments on offer and the lack of any guarantee that treatment will work in a particular case. Most young people are sad and ashamed about the bed-wetting and want it to stop, but they vary widely in their belief in their own capacity to influence the situation, and in their optimism about what the future holds. The problem can persist into adolescence or even adulthood, with far reaching social and emotional consequences, both for the young people and their families. In an ethnographic study involving 19 families 'perceived helplessness' emerged as a key issue permeating the whole system and often activating a downward spiral, leading to abdication of effort and responsibility by the young people themselves, by their parents and sometimes by health care professionals. Informed by the insights gained from this study and an extensive review of the literature on perceived control the Family Perspectives on Bed Wetting Questionnaire has been developed to explore family members' feelings, degree of concern and dimensions of perceived control relating to: effort, ability, luck, important others and the unknown. This questionnaire was used as a basis for structured interviews with family members in a longitudinal survey, involving 40 families attending one of nine community-based, nurse-led enuresis clinics in Greater Glasgow. It was found that only 38% of the young people were entering into treatment with the belief that they had the ability to be dry at night. This became self-fulfilling, with only 33% achieving initial success of 14 consecutive dry nights in a 16-week period (chi-squared test, P=0.029). Seventy per cent of young people felt that luck was important, while most parents felt that luck had little part to play. Implications for practice include the need to assess the families' readiness to engage in treatment, to create opportunities for effective control and to encourage realistic expectations.


Subject(s)
Enuresis/psychology , Enuresis/rehabilitation , Internal-External Control , Self Efficacy , Adolescent , Child , Child, Preschool , Enuresis/nursing , Female , Follow-Up Studies , Humans , Male , Nursing Assessment , Parents/psychology , Program Evaluation , Psychological Theory , Scotland
15.
J Physiol ; 525 Pt 1: 125-34, 2000 May 15.
Article in English | MEDLINE | ID: mdl-10811731

ABSTRACT

The active Ca2+ transport properties of malaria-infected, intact red blood cells are unknown. We report here the first direct measurements of Ca2+ pump activity in human red cells infected with Plasmodium falciparum, at the mature, late trophozoite stage. Ca2+ pump activity was measured by the Co2+-exposure method adapted for use in low-K+ media, optimal for parasitised cells. This required a preliminary study in normal, uninfected red cells of the effects of cell volume, membrane potential and external Na+/K+ concentrations on Ca2+ pump performance. Pump-mediated Ca2+ extrusion in normal red cells was only slightly lower in low-K+ media relative to high-K+ media despite the large differences in membrane potential predicted by the Lew-Bookchin red cell model. The effect was prevented by clotrimazole, an inhibitor of the Ca2+-sensitive K+ (KCa) channel, suggesting that it was due to minor cell dehydration. The Ca2+-saturated Ca2+ extrusion rate through the Ca2+ pump (Vmax) of parasitised red cells was marginally inhibited (2-27 %) relative to that of both uninfected red cells from the malaria-infected culture (cohorts), and uninfected red cells from the same donor kept under identical conditions (co-culture). Thus, Ca2+ pump function is largely conserved in parasitised cells up to the mature, late trophozoite stage. A high proportion of the ionophore-induced Ca2+ load in parasitised red cells is taken up by cytoplasmic Ca2+ buffers within the parasite. Following pump-mediated Ca2+ removal from the host, there remained a large residual Ca2+ pool within the parasite which slowly leaked to the host cell, from which it was pumped out.


Subject(s)
Calcium-Transporting ATPases/metabolism , Erythrocyte Membrane/metabolism , Plasmodium falciparum/parasitology , Animals , Biological Transport , Calcimycin/pharmacology , Calcium/metabolism , Clotrimazole/pharmacology , Cobalt/metabolism , Culture Media/chemistry , Erythrocyte Membrane/parasitology , Humans , Ionophores/pharmacology , Kinetics , Membrane Potentials
16.
Biochim Biophys Acta ; 1463(1): 88-98, 2000 Jan 15.
Article in English | MEDLINE | ID: mdl-10631297

ABSTRACT

The human malaria parasite, Plasmodium falciparum, induces in the plasma membrane of its host red blood cell new permeation pathways (NPP) that allow the influx of a variety of low molecular weight solutes. In this study we have demonstrated that the NPP confer upon the parasitised erythrocyte a substantial permeability to a range of monovalent organic (quaternary ammonium) cations, the largest having an estimated minimum cross-sectional diameter of 11-12 A. The rate of permeation of these cations showed a marked dependence on the nature of the anion present, increasing with the lyotropicity of the anion. There was no clear relationship between the permeation rate and either the size or the hydrophobicity of these solutes. However, the data were consistent with the rate of permeation being influenced by a combination of these two factors, with the pathways showing a marked preference for the relatively small and hydrophobic phenyltrimethylammonium ion over larger or less hydrophobic solutes. Large quaternary ammonium cations inhibited flux via the NPP, as did long-chain n-alkanols. For both classes of compound the inhibitory potency increased with the size and hydrophobicity of the solute. This study extends the range of solutes known to permeate the NPP of malaria-infected erythrocytes as well as providing some insight into the factors governing the rate of permeation.


Subject(s)
Erythrocyte Membrane/metabolism , Erythrocyte Membrane/parasitology , Plasmodium falciparum/pathogenicity , Animals , Cations/chemistry , Cations/metabolism , Cations/pharmacology , Cell Membrane Permeability/drug effects , Choline/pharmacokinetics , Erythrocyte Membrane/drug effects , Hemolysis , Humans , In Vitro Techniques , Magnetic Resonance Spectroscopy , Models, Molecular , Quaternary Ammonium Compounds/chemistry , Quaternary Ammonium Compounds/metabolism , Quaternary Ammonium Compounds/pharmacology
17.
Qual Health Care ; 8(2): 86-91, 1999 Jun.
Article in English | MEDLINE | ID: mdl-10557683

ABSTRACT

OBJECTIVE: To evaluate patients' views on the process and outcome of day surgery in Scotland, and to study patients' satisfaction with care in a range of specific procedures. DESIGN: Questionnaires completed by a census of day case surgery patients within a band of 25 procedures under the umbrella of five broad groups: (1) general surgery; (2) urology; (3) gynaecology; (4) orthopaedics; (5) ear, nose, and throat; ophthalmology. SETTING: 13 hospitals in six health board areas in Scotland. SUBJECTS: During the period 1995-6, 5069 day case patients were asked to complete a questionnaire within two weeks of their operation and discharge from hospital. MAIN OUTCOME MEASURES: Arrangements before admission; immediate postoperative symptoms and complications; problems experienced after discharge; readmission after discharge. RESULTS: A response rate of 68% was obtained from 13 sites ranging from 43% to 82%. The overall satisfaction score was 85. A total of 894 patients (26%) experienced pain after surgery and 783 (23%) had relatively minor medical problems after discharge. In total, 265 (7.8%) patients were readmitted to hospital after discharge. Few notable differences existed between specialties or hospitals in terms of satisfaction scores, although notable pain was experienced more frequently in gynaecology and general surgery patients. Readmission was more common for urological procedures. CONCLUSION: Overall, patient satisfaction with day case surgery was high. Dissatisfaction was largely related to waiting times between admission, operation, and discharge. The amount of pain experienced also had a notable impact on the level of patient satisfaction. Day surgery is not without complications, with 26% of patients experiencing notable degrees of pain; 23% having minor medical problems after discharge; and 8% of respondents having to reattend hospital with problems relating to their original operations.


Subject(s)
Ambulatory Surgical Procedures/standards , Outcome and Process Assessment, Health Care/statistics & numerical data , Patient Satisfaction/statistics & numerical data , Adolescent , Adult , Aged , Female , Health Care Surveys , Hospitals, Public/standards , Humans , Male , Middle Aged , Pain, Postoperative , Patient Discharge , Postoperative Complications , Scotland , Surveys and Questionnaires , Time Management , Waiting Lists
18.
J Membr Biol ; 172(1): 13-24, 1999 Nov 01.
Article in English | MEDLINE | ID: mdl-10552010

ABSTRACT

Previous reports have indicated that Plasmodium falciparum-infected red cells (pRBC) have an increased Ca(2+) permeability. The magnitude of the increase is greater than that normally required to activate the Ca(2+)-dependent K(+) channel (K(Ca) channel) of the red cell membrane. However, there is evidence that this channel remains inactive in pRBC. To clarify this discrepancy, we have reassessed both the functional status of the K(Ca) channel and the Ca(2+) permeability properties of pRBC. For pRBC suspended in media containing Ca(2+), K(Ca) channel activation was elicited by treatment with the Ca(2+) ionophore A23187. In the absence of ionophore the channel remained inactive. In contrast to previous claims, the unidirectional influx of Ca(2+) into pRBC in which the Ca(2+) pump was inhibited by vanadate was found to be within the normal range (30-55 micromol (10(13) cells. hr)(-1)), provided the cells were suspended in glucose-containing media. However, for pRBC in glucose-free media the Ca(2+) influx increased to over 1 mmol (10(13) cells. hr)(-1), almost an order of magnitude higher than that seen in uninfected erythrocytes under equivalent conditions. The pathway responsible for the enhanced influx of Ca(2+) into glucose-deprived pRBC was expressed at approximately 30 hr post-invasion, and was inhibited by Ni(2+). Possible roles for this pathway in pRBC are considered.


Subject(s)
Calcium/blood , Erythrocytes/metabolism , Erythrocytes/parasitology , Plasmodium falciparum/pathogenicity , Potassium/blood , Animals , Calcimycin/pharmacology , Cell Membrane Permeability/drug effects , Erythrocytes/drug effects , Humans , In Vitro Techniques , Ion Transport , Ionophores/pharmacology , Malaria, Falciparum/blood , Nickel/pharmacology , Plasmodium falciparum/growth & development , Potassium Channels/blood , Rubidium/pharmacokinetics
19.
Poult Sci ; 78(3): 428-36, 1999 Mar.
Article in English | MEDLINE | ID: mdl-10090271

ABSTRACT

Systems used to measure fertility in poultry have themselves presented a major impediment to progress in maintaining or improving fertility. Generally, these systems have been time-consuming, quantitatively inadequate, or both. A simplistic illustration of the basis of the problem is that if six fertile eggs were laid by a turkey hen during 1 wk after insemination, then all we know is what happened to six sperm: they fertilized the eggs. If 100 million sperm were inseminated, then information on the other 999,999,994 is missing. A better approach for quantitating breeding efficiency is to estimate the numbers of sperm that interact with the egg in the infundibulum. These can be identified in laid eggs, as sperm in the outer perivitelline layer (OPVL sperm), or holes produced by sperm in the inner perivitelline layer (IPVL holes). Eggs can contain up to 250,000 OPVL sperm, so the scale improves on binary estimation of fertilization status. The number of spermatozoa interacting with the perivitelline layer is related to the artificial insemination (AI) dose, the number of oviducal sperm, and the probability of fertilization, not just for one egg, but for subsequent eggs laid by the same hen. Practical applications of sperm:egg interaction measurements include: replacement of fertility trials for evaluation of semen; general fertility evaluation; and monitoring breeding efficiency of commercial turkey and broiler breeders. Furthermore, studies of sperm transfer into eggs raise interesting questions about the efficiency of turkey hens' response to AI or mating frequency of broiler hens in commercial flocks.


Subject(s)
Chickens/physiology , Fertility , Sperm-Ovum Interactions , Turkeys/physiology , Animal Husbandry/methods , Animals , Female , Male , Selection, Genetic
20.
Novartis Found Symp ; 226: 55-66; discussion 66-73, 1999.
Article in English | MEDLINE | ID: mdl-10645538

ABSTRACT

The malaria-infected erythrocyte shows an increased permeability to a wide range of solutes. The increase is mediated in part by parasite-induced new permeation pathways (NPP) and in part (for some solutes, under some conditions) by increased activity of endogenous transporters. The NPP provide the major route for the influx into the infected cell of a number of essential nutrients, but although the functional characteristics of these pathways are understood in some detail, they are yet to be identified at a molecular level. Lucifer yellow, a fluorescent anion, is taken up by malaria-infected erythrocytes to a much greater extent than uninfected erythrocytes via a pathway that differs in its pharmacological characteristics from the NPP. The nature, origin and location of this pathway remain to be established.


Subject(s)
Erythrocytes/parasitology , Host-Parasite Interactions , Plasmodium , Animals , Biological Transport, Active
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