Transmyocardial laser revascularisation in clinical practice.
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Angina Pectoris↗
Biomedical subjects
D J Wright
Publications and source records attributed to D J Wright.
The kinetic mechanism of EcoRI endonuclease.
Steady-state parameters governing cleavage of pBR322 DNA by EcoRI endonuclease are highly sensitive to ionic environment, with K(m) and k(cat) increasing 1,000-fold and 15-fold, respectively, when ionic strength is increased from 0.059 to 0.23 M. By contrast, pre-steady-state analysis has shown that recognition, as well as first and second strand cleavage events that occur once the enzyme has arrived at the EcoRI site, are essentially insensitive to ionic strength, and has demonstrated that the rate-limiting step for endonuclease turnover occurs after double-strand cleavage under all conditions tested. Furthermore, processive cleavage of a pBR322 variant bearing two closely spaced EcoRI sites is governed by the same turnover number as hydrolysis of parental pBR322, which contains only a single EcoRI sequence, ruling out slow release of the enzyme from the cleaved site or a slow conformational change subsequent to double-strand cleavage. We attribute the effects of ionic strength on steady-state parameters to nonspecific endonuclease.DNA interactions, reflecting facilitated diffusion processes, that occur prior to EcoRI sequence recognition and subsequent to DNA cleavage.
DNA, Bacterial↗
The inhibitory action of Mycobacterium ulcerans soluble factor on monocyte/T cell cytokine production and NF-kappa B function.
Buruli ulcer is a chronic and progressive necrotizing ulcer for which there is no medical treatment. Historically, a soluble toxin (factor) derived from the causative Mycobacterium ulcerans was found to induce the massive necrosis of skin and s.c. tissue seen in this condition. However, the persistence of the disease is thought to be caused by a lack of any immune response. We therefore investigated whether the factor was related to immunosuppression. A protocol to partially purify the factor was developed, and its effects on immune competent cells were tested. The factor produced >95% inhibition of LPS-induced release of TNF and IL-10 from human monocytes and caused a loss of adherence of these cells without cell death. The factor also blocked the production of IL-2 from activated T lymphocytes. The factor had no effect on TNF-induced cytotoxicity, but abrogated TNF-induced NF-kappa B activation. Surprisingly, a synergy was observed between the factor and phorbol ester-directed NF-kappa B activation. The factor had no effect on IL-1- or LPS-induced NF-kappa B activity, indicating selective activity of the factor. The factor did not inhibit the degradation of I kappa B alpha induced by TNF, indicating that the target for its activity lies within an undefined part of the TNF signaling mechanism. The data indicate that the localized immunosuppression associated with Buruli ulcer relates to the activity of the released factor, and this may provide a target for future therapeutic strategies for this intractable disease.
Animals↗
Increased incidence of infectious diseases during prospective follow-up of human T-lymphotropic virus type II- and I-infected blood donors. Retrovirus Epidemiology Donor Study.
BACKGROUND: To determine whether human T-lymphotropic virus type II (HTLV-II) infection is associated with an increased incidence of bacterial infections, we prospectively observed cohorts of HTLV-I- and HTLV-II-infected and seronegative subjects in 5 US cities. METHODS: Of 1340 present and former blood donors examined at enrollment, 1213 (90.5%) were re-examined after approximately 2 years, including 136 HTLV-I- and 337 HTLV-II-seropositive subjects and 740 demographically stratified HTLV-seronegative subjects. All subjects were seronegative for human immunodeficiency virus. Odds ratios (ORs) for incident disease outcomes were adjusted for covariates, including age, sex, race or ethnicity, education, and, if significantly associated with the outcome, blood center, donation type, income, smoking, alcohol intake, and injected drug use. RESULTS: Compared with seronegative status, HTLV-II infection was associated with an increased incidence of bronchitis (OR, 1.81; 95% confidence interval [CI], 1.20-2.75), bladder and/or kidney infection (OR, 1.94; 95% CI, 1.26-2.98), oral herpes infection (OR, 9.54; 95% CI, 3.33-27.32), and a borderline increased incidence of pneumonia (OR, 2.09; 95% CI, 0.92-4.76); HTLV-I infection was associated with an increased incidence of bladder and/or kidney infection (OR, 2.79; 95% CI, 1.63-4.79). One incident case of HTLV-I-positive adult T-cell leukemia was observed (incidence, 348 per 100,000 HTLV-I person-years), and 1 case of HTLV-II-positive tropical spastic paraparesis-HTLV-associated myelopathy was diagnosed (incidence, 140 per 100,000 HTLV-II person-years). CONCLUSIONS: These data support an increased incidence of infectious diseases among otherwise healthy HTLV-II- and HTLV-I-infected subjects. They are also consistent with the lymphoproliferative effects of HTLV-I, and with neuropathic effects of HTLV-I and HTLV-II.
Adolescent↗
Evaluation of spinning disc technology for the application of entomopathogenic nematodes against a foliar pest.
Two spinning disc spray application systems, the Micron Herbaflex and Micron Ulva+, were assessed for their potential for the application of infective juveniles (IJs) of entomopathogenic nematodes (EPNs) against larvae of the diamondback moth (DBM), Plutella xylostella. The effect of initial concentration of IJs on subsequent infection was examined for three species of EPNs: Steinernema sp. (M87), Steinernema sp. (SSL85), and Heterorhabditis sp. Increasing the concentration of IJs generally resulted in a significant increase in both DBM mortality and the mean number of nematodes per larva following spray application with the Micron Herbaflex sprayer. Application with the Micron Ulva+ was examined using two different initial concentration of IJs, which generally resulted in an increase in DBM mortality and intensity of infection. The effect of changing the flow rate to the Ulva+ was also examined. This generally resulted in increased DBM mortality as flow rate was increased but there was little change in the mean number of nematodes per host larva. The effect of addition of a number of adjuvants to the spray solution on subsequent infection showed that DBM mortality by the IJs was not significantly affected but that the mean number of nematodes infecting was significantly enhanced by some of the adjuvants. Desiccation survival studies with IJs of Heterorhabditis sp. following application with both sprayers onto Chinese cabbage leaf discs, with or without the addition of an adjuvant, showed that the survival time of 50% of IJs was over 3 h. Infection of DBM larvae was also assessed following desiccation on Chinese cabbage leaf discs. High levels of infection were attainable, in terms of resultant DBM mortality, for at least 150 min following spray application.
Animals↗
Changes in immune activation markers during pregnancy and postpartum.
Changes in CD4 + cell levels and other immune parameters have been reported to occur during pregnancy but the timing of these alterations and their relationship to changes in immune function have not been well characterized. In addition, the influence of sociodemographic, obstetric, and other covariates on these relationships is largely unknown. We measured three immune activation markers, soluble interleukin-2 receptor (sIL-2Ralpha), soluble CD8 antigen (sCD8), and neopterin during pregnancy and postpartum in 170 HIV-1-seronegative women enrolled in the Mothers and Infants Cohort Study. Ante-partum and postpartum changes in these markers were examined using multivariable longitudinal random effects models. Neopterin levels began to rise well before delivery and were in decline by 2 months postpartum. sIL-2Ralpha and sCD8 levels increased at or near delivery and peaked by 2 months postpartum. After adjustment for other variables, the peak in sIL-2Ralpha was greater among women with pre-term than full-term deliveries (P = 0.05). All three markers were higher in whites than non-whites and in 'hard' drug users than non-users (P < or = 0.001 for each). After adjustment for these and other variables, hepatitis C virus (HCV) seropositivity was associated with higher levels of sCD8 and neopterin (P < or = 0.001 for each) but not sIL-2Ralpha (P = 0.27). These longitudinal data indicate that a state of broad immune activation develops at or near delivery. A number of maternal variables appear to influence the magnitude of these changes.
Adult↗
Fatty acid composition of Heterorhabditis sp. during storage.
The fatty acid composition of three North West European isolates of Heterorhabditis sp. from different geographical origins, UK211 (England), HF85 (The Netherlands) and EU17 (Estonia) was assessed directly after harvest and, for UK211 and HF85, after 5 weeks storage in water at 20 degrees C. Lipid represented 34-43% of the dry weight of fresh nematodes. Of this, neutral lipid (NL) comprised from 70% (HF85) to over 90% (UK211, EU17). The fatty acid patterns were similar between the three isolates. Oleic (C18:In-9), palmitic (C16:0), and linoleic (C18:2n-6) acid predominated with 51, 13 and 12%, respectively in the total lipid (TL) of fresh nematodes (average for the three isolates). Levels of unsaturation (U.I.) of fresh nematodes were on average 110, 112, 113 and 152 for the TL, NL, phospholipid and free fatty acid fractions, respectively. EU17 had a slightly lower U.I than the other two strains, despite its more northern origin. Changes in fatty acid composition due to storage were most significant in the NL fraction. The U.I. for the NL fraction increased during storage, suggesting a preferential use of saturated fatty acids.
Animals↗
Clinical pharmacy interventions by community pharmacists during the dispensing process.
AIMS: To evaluate the professional contact between the community pharmacist and general practitioner during the dispensing process on issues other than the legality or simple clarification of the prescription. METHODS: Fourteen community pharmacists from five adjacent localities completed details of each clinical pharmacy intervention during 1 week of each month for a period of 1 year. Each week of the month was randomly selected. When a community pharmacist had to contact the prescriber, during the dispensing of a prescription, the following data were recorded: brief patient details, the prescribed drug therapy, the reason for intervention, the outcome and the time taken. The main outcome measures were the type and nature of each intervention, the BNF category of the drug involved and the time taken. A multidisciplinary clinical panel assessed the potential of each intervention to alter the outcome of the patient's clinical management and to prevent a drug related hospital admission. These assessments were ranked between 0 and 10 (100% confident). RESULTS: During a period covering 1 week per month over 1 year, 1503 clinical pharmacy interventions were made out of 201 000 items dispensed. When normalized for the dispensing volume of each community pharmacy the lower the number of items dispensed then the greater was the percentage of interventions (P=0.013). The clinical panel decided that between 19 (0.01% of the total items dispensed) and 242 (0.12%) interventions may have prevented a drug-related hospital admission, 71 (0.04%) to 483 (0.24%) could have prevented harm whilst 103 (0.05%) to 364 (0.18%) had the potential to improve the efficacy of the intended therapeutic plan. The panel also decided that 748 (0.37%) interventions improved the clinical outcome and could have saved a visit to or by the general practitioner. Conclusion Clinical pharmacy provided by a community pharmacist during the dispensing process has the potential to provide a valuable contribution to health care.
Community Pharmacy Services↗
Correlation of quantitative bone marrow and blood cultures in AIDS patients with disseminated Mycobacterium avium complex infection.
The relationship between Mycobacterium avium complex (MAC) infection of blood and bone marrow was studied in human immunodeficiency virus-infected patients before and during treatment. Quantitative cultures were obtained at baseline from 17 persons with newly detected MAC bacteremia. Serial blood cultures were obtained, and a second bone marrow sample was obtained at 4 or 8 weeks. At baseline, the median MAC load in bone marrow core samples was 3 log10 higher than in blood. Bone marrow MAC loads ranged widely (866-847,315 cfu/g), and no significant correlation was found between MAC load in blood and that in bone marrow core samples. MAC loads in bilateral bone marrow biopsy samples from 7 subjects were highly correlated. MAC loads declined in blood and bone marrow at similar rates during therapy, but blood was sterilized before bone marrow. Length of survival was inversely associated with initial bone marrow core MAC load but not with blood MAC load. Initiation of treatment when tissue MAC load is low may increase the likelihood of favorable clinical outcome.
AIDS-Related Opportunistic Infections↗
Successful in vitro cultivation of Borrelia duttonii and its comparison with Borrelia recurrentis.
Borrelia duttonii, the cause of East African tick-borne relapsing fever, has until now been refractory to growth in laboratory media. This spirochaete has only be propagated in mice or by tissue culture, restricting both yield and purity of cells available for research. The successful isolation of five clinical isolates of B. duttonii from patients in Central Tanzania and their comparison with Borrelia recurrentis is reported. Electron microscopy revealed spirochaetal cells with pointed ends, a mean wavelength of 1.8 microns with an amplitude of 0.8 micron, similar to the findings for B. recurrentis. Cells contained 10 periplasmic flagella inserted at each end of the spirochaete, again comparable with the counts of 8-10 flagella found in B. recurrentis. PFGE revealed a chromosome of approximately 1 Mb, a large plasmid of approximately 200 kb, and a small plasmid of 11 kb in all strains of B. duttonii and in B. recurrentis. B. duttonii possessed a further 7-9 plasmids with sizes ranging from 20 to 90 kb. In two isolates of B. duttonii, the profiles were identical. In contrast, all 18 isolates of B. recurrentis fell into one of five plasmid patterns with 3-4 plasmids ranging from 25 to 61.5 kb in addition to those of 11 and 200 kb described above. Analysis of the SDS-PAGE profiles of B. duttonii strains revealed a high-molecular-mass band of 33.4-34.2 kDa in four strains (variable large protein, VLP) and a low-molecular-mass band of 22.3 kDa in the remaining strain (variable small protein, VSP). This resembles the protein profiles found in B. recurrentis. The G + C ratio of B. duttonii was 27.6 mol%. Nucleotide sequence of the rrs gene (16S rRNA) from four B. duttonii isolates revealed 100% identity among these strains and 99.7% homology with three strains deposited by others in GenBank. The rrs gene of eight representative clinical isolates of B. recurrentis confirmed their close similarity with B. duttonii.
Bacteriological Techniques↗
The role of exercise testing in the evaluation and management of heart failure.
The clinical syndrome of heart failure has been investigated so extensively that it may now almost be regarded as a metabolic disorder. Although an initial insult reduces cardiac pump efficacy, the resultant physiological response culminates in complex neurohormonal dysfunction. This has created confusion and prevented the acceptance of a universal definition of cardiac failure. With much current research concentrating on the pharmacological modification of neuroendocrine imbalance, it is easy to lose sight of the fundamental principles behind heart failure management, namely, to improve cardiac function. In attempting to achieve this, the issues of morbidity and mortality must be addressed jointly; they are not mutually exclusive entities. Discrepant results between mortality studies and changes in exercise capacity have undermined the value of exercise testing. Because a treatment enhances longevity we should not ignore its effect on symptomatic status, and likewise we should not discard a therapy, which improves function because adverse events result in occasional premature deaths. Informed patient choice must exist. Historically, exercise testing has been quintessential in our understanding and evaluation of heart failure. Peak oxygen consumption remains the best overall indicator of symptomatic status, exercise capacity, prognosis and hospitalisation. Unfortunately, muddling of surrogate and true end-points has confused many of these issues. Improved comprehension may be gained by applying the concept of cardiac reserve which has been described in a variety of heart conditions and used in cardiac failure patients to provide an indication of prognosis and functional capacity.
Exercise Test↗
Cardiac rehabilitation: are the potential benefits being realized?
Cardiac rehabilitation or exercise training programmes are provided by many hospitals. This article discusses the evidence supporting the implementation of such facilities and reviews the reality of services in the UK.
Coronary Disease↗
Developing an effective research question.
Ideas for research can come from numerous sources, and should be explored in depth to identify key areas for research. Question stems can be used to generate the research question. The research question must be carefully worded to avoid misinterpretation and ambiguities.
Algorithms↗
The influence of pregnancy on human immunodeficiency virus type 1 infection: antepartum and postpartum changes in human immunodeficiency virus type 1 viral load.
OBJECTIVE: Our objective was to examine the influence of pregnancy on human immunodeficiency virus type 1 viral load by measuring human immunodeficiency virus type 1 ribonucleic acid levels during pregnancy and post partum. STUDY DESIGN: One or more plasma or serum specimens obtained before and during the third trimester, and at 2, 12, and 24 months post partum were available for 160 human immunodeficiency virus type 1-seropositive women enrolled in the Mothers and Infants Cohort Study between January 1986 and January 1991. All specimens were frozen and stored at -70 degrees C until analyzed in batch for human immunodeficiency virus type 1 ribonucleic acid by polymerase chain reaction. A multivariate longitudinal random effects model was developed to examine changes in human immunodeficiency virus type 1 ribonucleic acid levels over time. RESULTS: Overall, human immunodeficiency virus type 1 ribonucleic acid levels rose significantly during the study period, particularly during the second year post partum (mean, 0.09 log per year; 95% confidence interval, 0.03 to 0.15 logs per year; p = 0.005). However, the mean slope during pregnancy was not significantly different from zero (p = 0.65). CONCLUSION: Pregnancy had little immediate effect on human immunodeficiency virus type 1 viral load in most human immunodeficiency virus type 1-seropositive women.
Acquired Immunodeficiency Syndrome↗
The ultrastructure of the cuticle and sheath of infective juveniles of entomopathogenic steinernematid nematodes.
The ultrastructure of the cuticle of infective juveniles (IJs) of Steinernema carpocapsae (newly emerged and 80-day-old) and newly emerged IJs of S. riobravis, S. feltiae and S. glaseri was examined using transmission electron microscopy. The thickness of four distinctive layers of the cuticle was measured: epicuticle, cortical and median layer, striated layer and fibrous mat. The thickness of the cuticle was correlated with the size of the IJ. In the case of newly emerged IJs, the smallest species, S. carpocapsae, had a cuticle thickness of c. 270 nm compared with c. 460 nm for S. glaseri, the largest of the four species. The overall thickness of the cuticle or the thickness of the cuticle layers was not correlated with the ability of the IJs of the four species to survive desiccation per se. The major difference between newly emerged IJs of the four species was that S. carpocapsae had a proportionately thicker striated layer compared with the other three species. The significance of this is not known but it may be an adaptation involving the nictation behaviour of this species. A substantial change was observed in the cuticle of aged (80-day-old) IJs of S. carpocapsae, whereby the thickness of the cortical and median layer increased by more than 100% and the overall thickness of the cuticle increased by about 50%. Two possible explanations for this increase are: (i) new material was synthesized; or (ii) the fluid content of this layer increased due to an increase in the permeability of the outer layers of the cuticle. The ultrastructure of the sheaths of S. feltiae and S. glaseri was also examined and, apart from S. glaseri having a thicker sheath, the structure of the sheath in both species was similar, with the epicuticle and striated layer still visible.
Aging↗
Changes in the lipid content and fatty acid composition of 2nd-stage juveniles of Globodera rostochiensis after rehydration, exposure to the hatching stimulus and hatch.
The total lipid content of the dry weight of whole cysts and 2nd-stage juveniles (J2) of Globodera rostochiensis was 17.1% in dry cysts, 20.9% in cysts soaked in distilled water (DW), 20.3% in cysts that had been in potato root diffusate (PRD) for 7 days, 7.3% in cysts that had been in PRD for 28 days and 29.2% for hatched J2. The fatty acid composition of the total lipid did not differ between dry cysts, cysts in DW and cysts in PRD for 7 days. However, major differences in the fatty acid composition of all lipid classes were found between rehydrated cysts in PRD and freshly hatched J2. After hatching, the degree of saturation and the percentage of monounsaturated fatty acids decreased and the percentage of polyunsaturated fatty acids increased considerably, especially in the free fatty acid fraction, where C20:1 showed an 8-fold decrease and C20:4 a 33-fold increase. There was a difference in the fatty acid composition of cysts in PRD for 7 days and cysts in PRD for 28 days (after most of the J2 had hatched); with increased time in PRD the percentage of polyunsaturated fatty acids increased and the percentage of monounsaturated fatty acids decreased in all lipid classes. Differences in the fatty acid profiles between cysts in PRD for 28 days and hatched J2 were found mainly in the free fatty acid and the non-acidic phospholipid fractions. The free fatty acid fraction of the cysts was dominated by monounsaturated fatty acids (52%), whereas the same fraction of hatched J2 contained large amounts of polyunsaturated fatty acids (60%). These polyunsaturated fatty acids, especially C20:4, might play an important part in nematode-plant interactions during infection.
Analysis of Variance↗
Variable major lipoprotein is a principal TNF-inducing factor of louse-borne relapsing fever.
Massive release of tumor necrosis factor is responsible for the potentially fatal larisch-Herxheimer reaction that follows antibiotic treatment of relapsing fever due to Borrelia recurrentis. We have undertaken the quantitative purification of the components of B. recurrentis that stimulate human monocytes to produce tumor necrosis factor. We show that the predominant factor inducing tumor necrosis factor is a variable lipoprotein homologous to the variable major protein of B. hermsii. We found antibodies to different forms of variable major protein in two patients with louse-borne relapsing fever. The three purified variable major proteins studied here differ in their ability to induce tumor necrosis factor production, which may partly explain the variable clinical severity of borrelial infection. These results may be of considerable relevance for the pathogenesis of Lyme disease and other forms of human borreliosis.
Amino Acid Sequence↗
Should exercise blood pressure be measured in clinical practice?
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Blood Pressure↗