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D J Wright

Publications and source records attributed to D J Wright.

At least 91 records · Page 5Linked to original sources

The routine use of sublingual GTN with resting 99Tcm-tetrofosmin myocardial perfusion imaging.

Nitrates can be used to improve resting myocardial blood flow in patients with severe coronary artery disease. This may enhance tracer uptake during rest myocardial perfusion imaging. Recent studies using nitrates at rest have shown increased detection of reversible ischaemia in this patient group with the 201Tl and 99Tcm perfusion tracers MIBI and tetrofosmin. However, it is not always possible to assess the severity of coronary artery disease before the rest injection and therefore whether a patient would benefit from nitrate administration. To improve the sensitivity for the detection of reversible ischaemia and to avoid a repeat study with nitrates (especially in patients with 'fixed' defects), a protocol in which all patients routinely receive nitrates prior to the rest injection is required. This prospective study evaluated the effect of nitrate administration prior to rest imaging in a randomly selected group of patients. Thirty patients selected at random from routine referrals had stress, rest and rest + GTN tetrofosmin imaging on three separate days. Changes in reversibility between the rest and rest + GTN images were assessed both visually and using semi-quantitative analysis. Defects at stress were seen in 43 coronary artery territories, 33 of which were reversible at rest and 37 reversible at rest + GTN. Of these 43 defects, 82% demonstrated either increased or the same degree of reversibility at rest + GTN imaging compared to standard rest imaging. All defects with reduced reversibility at rest + GTN imaging (i.e. the remaining 18%) were, however, still reversible compared to the stress images. Some of this reduced reversibility may be due to attenuation artefacts. We conclude that the routine use of GTN with rest tetrofosmin imaging will result in increased detection of ischaemic areas with no loss of sensitivity or specificity.

Administration, Sublingual↗

Cortisol is higher in parkinsonism and associated with gait deficit.

INTRODUCTION: We propose an active pathogenic mechanism, involving circulating cortisol, in parkinsonism. MATERIALS AND METHODS: Serum cortisol was measured in 96 subjects with idiopathic parkinsonism, 170 without, and in 17 spouses and 36 siblings of elderly sufferers with double the number of controls, all obeying inclusion/exclusion criteria. RESULTS: Cortisol, adjusted for sampling time, was greater (17%, on average, P<0.001) in parkinsonians, but not in relatives. The central cortisol lowering effect of anti-muscarinics was seen (P=0.025). Selegiline may attenuate the disease, and parkinsonism is less frequent in tobacco smokers. Selegiline was associated with a lower cortisol (P=0.03): chronic smoking appeared (P=0.08) to be, irrespective of parkinsonism. Bowel stasis has been implicated in the pathogenesis: cortisol was higher in parkinsonians requiring laxatives (P=0.05). In controls, cortisol was lower, the longer the stride (P=0.02): in parkinsonians, this relationship was numerically reversed. A similar (P=0.01) group performance interaction was seen for deterioration, over 4 years, in gait. CONCLUSION: Cortisol is doing harm or mirroring something which is. A common pathway for neuronal protection/rescue emerges.

Adult↗

Physiological cardiac reserve: development of a non-invasive method and first estimates in man.

OBJECTIVE: To investigate whether physiological cardiac reserve can be measured in man without invasive procedures and whether it is a major determinant of exercise capacity. DESIGN: Development of method of measurement and an observational study. SETTING: A regional cardiothoracic centre. SUBJECTS: 70 subjects with a wide range of cardiac function, from heart failure patients to athletes. METHODS: Subjects underwent treadmill, symptom limited cardiopulmonary exercise tests to measure aerobic exercise capacity (represented by VO2max) and cardiac reserve. Cardiac output was measured non-invasively using the CO2 rebreathing technique. RESULTS: Cardiac power output (CPOmax) at peak exercise was found to be significantly related to aerobic capacity: CPOmax (W) = 0.35 + 1.5 VO2max (1/min), r = 0.87, p < 0.001. It also correlated well with exercise duration (r = 0.62, p < 0.001), suggesting that cardiac reserve is a major determinant of exercise capacity. In the study, cardiac reserve ranged from 0.27 to 5.65 W, indicating a 20-fold difference between the most impaired cardiac function and that of the fittest subject. CONCLUSIONS: A non-invasive method of estimating physiological cardiac reserve was developed. The reserve was found to be a major determinant of exercise capacity in a population of normal subjects and patients with heart disease. This method may thus be used to provide a clearer definition of the extent of cardiac impairment in patients with heart failure.

Adolescent↗

Expression of myosin heavy chain isoforms during development of domestic pigeon pectoralis muscle.

The pectoralis muscle of birds provides virtually all the power for the downstroke of the wing during flight. In adults it consists almost entirely of FOG (fast-twitch oxidative-glycolytic) and/or FG (fast-twitch glycolytic) fiber types. The aims of this study are to contrast MyHC (myosin heavy chain) transitions occurring within avian FG and FOG fibers during development, and to test the hypothesis that the pectoralis matures before the acquisition of flight. Pectoralis was obtained from pigeons (Columba livia) aged from 13 days in ovo to adult. Monoclonal antibodies generated against chicken MyHC isoforms were used with Western blots and immunocytochemistry. FG and FOG fibers were differentiated using a histochemical method demonstrating NADH (nicotinamide adenine dinucleotide), and "lesser fiber diameters" were quantified. Western blots confirm that the antibodies label pigeon MyHCs. A small number of the fibers are slow type in ovo, but these are quickly restricted in distribution and lost after hatching. In ovo fast-twitch fibers contain a ventricular isoform, and at least two embryonic-neonatal forms (designated E-N103 and E-N165). One week after hatching, fast-twitch fibers can be distinguished by NADH as FG or FOG. At fledging, four weeks after hatching, FG and FOG fibers are smaller than in older birds and E-N103 and E-N165 persist in both fibertypes. E-N103 wanes in all fibers shortly after fledging. E-N165 gradually disappears from FG fibers. Thus, despite pigeons being at adult body mass at fledging, their pectoralis is not fully mature.

Animals↗

The safety and pharmacokinetics of single-agent and combination therapy with megestrol acetate and dronabinol for the treatment of HIV wasting syndrome. The DATRI 004 Study Group. Division of AIDS Treatment Research Initiative.

This randomized, open-labeled, multicenter study was designed to assess safety and pharmacokinetics of dronabinol (Marinol) tablets and megestrol acetate (Megace) micronized tablets, alone and in combination, for treatment of HIV wasting syndrome. Weight and quality of life data were also collected. Fifty-two patients (mean CD4+ count, 59 cells/microliter) were randomized to one of four treatment arms: dronabinol 2.5 mg twice/day (D); megestrol acetate 750 mg/day (M750); megestrol acetate 750 mg/day+dronabinol 2.5 mg twice/day (M750+D); or megestrol acetate 250 mg/day+dronabinol 2.5 mg twice/day (M250+D). After therapy initiation, 47 patients returned for at least one visit, and 39 completed the planned 12 weeks of study visits. Occurrence of adverse events, drug discontinuation, new AIDS-defining conditions, or CD4+ T lymphocyte changes were not statistically significantly different among arms. Serious adverse events assessed as related to dronabinol included CNS events (e.g., confusion, anxiety, emotional lability, euphoria, hallucinations) and those assessed as related to megestrol acetate included dyspnea, liver enzyme changes, and hyperglycemia. The mean weight change +/- SE over 12 weeks was as follows: D, -2.0 +/- 1.3 kg; M750, +6.5 +/- 1.1 kg; M750+D, +6.0 +/- 1.0 kg; and M250+D, -0.3 +/- 1.0 kg (difference among treatment arms, p = 0.0001). Pharmacokinetic parameters measured after 2 weeks of therapy for M750 were Cmax = 985 ng/ml and AUC = 22,487 ng x hr/ml, and for dronabinol and its active metabolite (HO-THC), respectively, were Cmax = 2.01; 4.61 ng/ml and AUC = 5.3; 23.7 ng x hr/ml. For megestrol acetate, but not dronabinol, there was a positive correlation at week 2 between both Cmax and AUC with each of the following: (1) weight change, (2) breakfast visual analog scale for hunger (VASH) score, and (3) dinner VASH score.

Adolescent↗

Risk factors for human T-cell lymphotropic virus types I and II (HTLV-I and -II) in blood donors: the Retrovirus Epidemiology Donor Study. NHLBI Retrovirus Epidemiology Donor Study.

In the United States, blood donors have been routinely screened for human T-cell lymphotropic virus (HTLV) since 1988. HTLV-I and -II seropositive blood donors have been identified through confirmatory testing at five participating blood centers and frequency-matched seronegative controls provided information on potential HTLV sociodemographic, parenteral, and sexual risk factors during structured interviews. After adjustment, low educational attainment; accidental needlesticks or cuts; prior blood transfusion; > or = 7 sex partners; and a sex partner from an HTLV-I endemic area were significantly associated with both HTLV-I and -II. Gender did not modify the odds ratios (OR) in the final logistic regression models, despite apparent male-female differences in gender-specific bivariable analysis. Injection drug use (IDU) or having sex with an IDUs were significant risks for HTLV-II, but not for HTLV-I. The OR for donors who had IDU sex partners was 20.6 times higher than those who did not. For IDUs, the OR was increased 10.5 times over nonusers. Abortion was a significant HTLV-II risk factor for women. Our findings indicate that IDU and sex with IDUs are important risk factors for HTLV-II transmission, even among low-risk populations such as blood donors.

Adult↗

Desiccation survival and water contents of entomopathogenic nematodes, Steinernema spp. (Rhabditida:Steinernematidae).

The survival of exsheathed infective juveniles (IJs) of 4 Steinernema species, S. glaseri (NC), S. feltiae (UK76), S. carpocapsae (All) and S. riobravis (Biosys355), was assessed following fast and slow drying on glass slides and 1% (w/v) agarose, respectively. Freshly harvested and aged (75-day-old) IJs were desiccated on glass slides after removal of superficial water, at 0, 20, 40, 60 and 80% relative humidity (r.h.). Survival was assessed after rehydration with water, and movement was used as the criterion for survival. Evidence for an intrinsic mechanism to control water loss and survive desiccation was found in freshly harvested S. carpocapsae IJs. At all r.h.s tested, S. carpocapsae had the greatest survival and the slowest rate of water loss. For example, at 80% r.h. the survival time for 50% (S50) of S. carpocapsae IJs was ca. 45 min compared with 5-20 min for the other species. Survival of aged IJs was markedly reduced in the case of S. carpocapsae and S. riobravis, and to a lesser extent in S. feltiae and S. glaseri. The 2nd stage juvenile cuticle (sheath) was not important in aiding desiccation survival of S. carpocapsae and S. glaseri. Drying IJs slowly on 1% agarose at 80% r.h. greatly improved the survival of all 4 species, particularly S. glaseri and S. feltiae. The work is discussed in relation to possible mechanisms for survival of IJs during fast and slow drying.

Acclimatization↗

Fatty acid composition of neutral lipid energy reserves in infective juveniles of entomopathogenic nematodes.

The fatty acid composition of neutral lipids from infective juveniles (IJs) of Steinernema carpocapsae strain All, S. riobravis strain Biosys 355, S. feltiae strain UK76, and S. glaseri strain NC stored in distilled water at 25 degrees C was determined. Newly emerged IJs of all four species had similar neutral lipid fatty acid profiles and of the 18 fatty acids identified, C18:1n-9 (43-49 mol %), C16:0 (18-23%), C18:2n-6 (8-14%) and C18:0 (4-8%) were the most abundant. Unsaturated fatty acids predominated, with about 50% being monoene and 14-22% polyene; the unsaturation index ranged from 91.6 in S. glaseri to 111.6 in S. carpocapsae. The fatty acid composition of the total lipid and the free fatty acid fraction mirrored that of the neutral lipids. During storage, the relative levels (%) of C16:0, C18:0, and C18:ln-9 in the neutral lipids declined significantly, suggesting they were preferentially utilised.

Animals↗

Relative importance of neutral lipids and glycogen as energy stores in dauer larvae of two entomopathogenic nematodes, Steinernema carpocapsae and Steinernema feltiae.

The infectivity of Steinernema carpocapsae dauer larvae (infective juveniles) remained nearly constant up to 60 days of storage in water at 25 degrees C and then declined rapidly over the next 30 days. Few individuals remained infective after 120 days. Concurrent measurements showed that the mean neutral lipid content of individual S. carpocapsae declined to about 10% of initial levels after 60 days, and staining of individual nematodes with Oil Red O indicated that the population was almost homogeneous for low levels of neutral lipids. In contrast, the mean glycogen content of S. carpocapsae only declined significantly between 60 and 90 days of storage. These results show that the decline in infectivity in S. carpocapsae is correlated primarily with the decline in glycogen reserves and suggests that glycogen is the key late energy store in aged infective juveniles. In contrast, Steinernema feltiae dauer larva showed a much more gradual decline in infectivity over a 150- to 180-day storage period with a concurrent decline in neutral lipids, whereas glycogen levels declined up to 90 days of storage and then remained nearly constant. Thus, unlike S. carpocapsae, neutral lipids remain an important energy store in S. feltiae during storage, although glycogen also appears to be important, at least initially.

Animals↗

Phospholipids and their fatty acids in infective juveniles of entomopathogenic steinernematid nematodes.

The composition of phospholipids and their fatty acids was investigated in the infective juveniles (IJs) of four species of entomopathogenic nematodes: Steinernema carpocapsae (strain All), S. riobravis (strain Biosys 355), S. feltiae (strain UK76) and S. glaseri (strain NC). In newly emerged IJs of the four species, phospholipids comprised 15-18% dry weight of the total lipids (or 5-6% dry weight of the nematode), and phosphatidylethanolamine and phosphatidylcholine constituted about 40 and 30%, respectively, of the total phospholipids, with phosphatidylserine (PS) and phosphatidylinositol (PI) collectively accounting for about 25%. Qualitatively, the four species had identical total phospholipid (combined non-acidic and acidic fractions) fatty acid profiles, although there were some differences in the relative proportions (mol%) of specific fatty acids. The fatty acid composition of the total phospholipids in newly emerged IJs was dominated by C16 fatty acids, specifically C16:0 (14-18%), C16:1n-7 (up to 20%) and C16:4 (up to 26%), whereas the major C18 fatty acid was C18:1n-9 (20-23%). Polyunsaturated C20 fatty acids collectively made up 8-13% of the total composition. When newly emerged IJs were stored in distilled water at 25 degrees C, the proportions of C16:0 and C16:4 decreased with storage time, whereas C16:3n-3 increased (by 30-fold in S. glaseri). These changes were mostly observed in the acidic phospholipid fraction (mainly PI and PS). No evidence was found for a correlation between the fatty acid composition of the phospholipids and the relative ability of the IJs of the four Steinernema species to survive desiccation stress.

Animals↗

Desiccation survival of populations of the entomopathogenic nematodes Steinernema feltiae and Heterorhabditis megidis from Greece and the UK.

The desiccation survival and ability to control water loss during drying of individual infective juveniles (IJs) of populations of Steinernema feltiae and Heterorhabditis megidis from Greece and the UK were examined at different relative humidities. Survival at all relative humidities was for minutes only and there was no evidence of enhanced survival of the populations of either species from Greece compared with those from the UK. The survival of individuals of both populations of H. megidis was superior to that of S. feltiae and the rate of drying of H. megidis was significantly slower. The sheath surrounding the IJs of H. megidis appears to be involved in slowing the rate of water loss of the enclosed nematodes.

Animals↗

Neutral lipids and the assessment of infectivity in entomopathogenic nematodes: observations on four Steinernema species.

An 8-point visual index was developed for Oil Red O staining of neutral lipids in infective juveniles (IJs) of Steinernema carpocapsae (A11), S. riobravis (Biosys 355), S. feltiae (UK76) and S. glaseri (NC). The visual index was found to be a reliable and rapid method for determining the relative neutral lipid content of individual IJs and was validated quantitatively by gas chromatography. The relationship between neutral lipid utilization and infectivity of IJs stored in distilled water at 25 degrees C was also investigated and the first quantitative results on neutral lipid utilization in entomopathogenic nematodes are reported. Neutral lipid contents of freshly harvested IJs of S. carpocapsae, S. riobravis. S. feltiae and S. glaseri were 31, 31, 24 and 26% dry wt, respectively. Steinernema carpocapsae showed a sigmoidal pattern for neutral lipid utilization while S. riobravis used neutral lipids at an almost constant rate. Survivorship of these two species ranged between 120 and 135 days, whereas S. feltiae and S. glaseri lived > 450 days and had a slower rate of lipid utilization during a 260 day storage period. Oil Red O staining showed that individual IJs in each population utilized lipids at different rates, even though they had the same initial lipid index. The infectivity of S. riobravis, S. feltiae and S. glaseri declined with lipid utilization. In contrast, S. carpocapsae maintained a high level of infectivity even at relatively low lipid levels. Therefore, neutral lipid content was found to be a suitable indicator of infectivity for S. riobravis, S. feltiae and S. glaseri but not for S. carpocapsae.

Animals↗

Increased prevalence of infectious diseases and other adverse outcomes in human T lymphotropic virus types I- and II-infected blood donors. Retrovirus Epidemiology Donor Study (REDS) Study Group.

Disease associations of human T lymphotropic virus types I and II (HTLV-I and -II) infection were studied in 154 HTLV-I-infected, 387 HTLV-II-infected, and 799 uninfected blood donors. Adjusted odds ratios (ORs) and 99% confidence intervals (CIs) were derived from logistic regression models controlling for demographics and relevant confounders. All subjects were human immunodeficiency virus type 1-seronegative. HTLV-II was significantly associated with a history of pneumonia (OR, 2.6; 99% CI, 1.2-5.3), minor fungal infection (OR, 2.9; 99% CI, 1.2-7.1), and bladder or kidney infection (OR, 1.6; 99% CI, 1.0-2.5) within the past 5 years and with a lifetime history of tuberculosis (OR, 3.9; 99% CI, 1.3-11.6) and arthritis (OR, 1.8; 99% CI, 1.2-2.9). Lymphadenopathy (> or =1 cm) was associated with both HTLV-I (OR, 6.6; 99% CI, 2.2-19.2) and HTLV-II (OR, 2.8; 99% CI, 1.1-7.1) infection, although no case of adult T cell leukemia/lymphoma was diagnosed. Urinary urgency and gait disturbance were associated with both viruses. This new finding of increased prevalence of a variety of infections in HTLV-II-positive donors suggests immunologic impairment.

Adolescent↗

Influence of other maternal variables on the relationship between maternal virus load and mother-to-infant transmission of human immunodeficiency virus type 1.

To assess the relationship between maternal human immunodeficiency virus (HIV) type 1 RNA level, other important covariates, and mother-to-infant (vertical) transmission of HIV-1, third trimester repository specimens from 160 HIV-1-seropositive women enrolled in the Mothers and Infants Cohort Study between 1986 and 1991 were assayed in batch for HIV-1 RNA. A significant association between peripheral blood HIV-1 RNA level and vertical transmission remained after controlling for CD4 cell level, duration of ruptured membranes, "hard" drug (cocaine and heroin) use, and frequency of sexual activity during pregnancy. However, the association was attenuated among women with advanced HIV infection and those with a high frequency of sexual activity during pregnancy. In these settings, interventions that target risk factors other than virus load may be particularly important for preventing vertical transmission of HIV-1.

Acquired Immunodeficiency Syndrome↗

Coordinate developmental expression of genes regulating sterol economy and cholesterol side-chain cleavage in the porcine ovary.

To investigate the coordinate developmental expression of low-density lipoprotein (LDL) receptor, 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, sterol carrier protein 2 (SCP2), steroidogenic acute regulatory protein (StAR), and cytochrome P450 side-chain cleavage (P450scc) enzyme messages throughout the pig estrous cycle, RNase protection analysis was performed using homologous (partially cloned) porcine sequences. Total RNA was isolated from ovarian tissues from unstimulated prepubertal gilts and gilts stimulated with eCG (Day -3) and hCG (Day 0) to induce follicular growth and ovulation. Specific transcripts (relative to 18S rRNA) were quantified in immature ovaries, preovulatory follicles (> or = 5 mm), corpora lutea (CL), and corpora albicantia. As an index of steroidogenesis, tissue progesterone content (per microgram protein) was low in the unstimulated ovary and preovulatory follicles, and it began to increase 4 days post-hCG, peaked at 12 days, and returned to preovulatory concentrations by 20 days post-hCG. HMG-CoA reductase mRNA was expressed at low levels and did not change significantly throughout the estrous cycle. The amount of LDL receptor mRNA increased approximately 6-fold after eCG stimulation and was expressed at similar concentrations in both preovulatory follicles and functional CL. Expression of SCP2 mRNA did not differ among the four tissue types but tended to be highest in midcycle (Day 12) CL compared other stages of CL (p = 0.007). StAR mRNA expression was minimal in unstimulated ovaries, was higher in preovulatory follicles (p = 0.014), and then rose again in CL (p = 0.009 compared with unstimulated ovary). P450scc mRNA concentrations were low in unstimulated ovaries, increased in preovulatory follicles (p = 0.044), and increased further in CL (p = 0.001 compared with preovulatory follicles). P450scc and StAR mRNA levels correlated with progesterone levels (r = +0.37, p = 0.025, and r = +0.71, p < 0.001, respectively). The expression of LDL receptor, StAR, and P450scc messages showed a dramatic decline by Day 20 post-hCG (p = 0.002, p = 0.003, p = 0.006, respectively, compared with CL) corresponding with functional regression of the CL. In summary, P450scc and StAR message expression are coordinately amplified during the pig follicular and luteal phase, whereas LDL receptor message after an initial increase is expressed at constitutively high levels, thus indicating a differential regulation of ovarian sterol-metabolizing genes during the steroidogenic life of the follicle and CL.

Animals↗

Borrelia recurrentis characterization and comparison with relapsing-fever, Lyme-associated, and other Borrelia spp.

Borrelia recurrentis, the cause of louse-borne relapsing fever, has until recently been considered noncultivable, which has prevented characterization of this spirochete. We successfully cultivated 18 strains from patients with louse-borne relapsing fever and present the initial characterization of these isolates. Electron microscopy revealed spirochetal cells with pointed ends, an average wavelength of 1.8 microns, an amplitude of 0.8 micron, and 8 to 10 periplasmic flagella. The G+C ratio was 28.4 mol%. Whole DNA-DNA hybridizations showed similarity between the isolates of B. recurrentis but not with Borrelia hermsii, Borrelia parkeri, Borrelia turicatae, or the Lyme-associated borreliae. Sequencing studies of both the flagellin and 16S RNA genes revealed that the greatest similarity was between B. recurrentis and Borrelia duttonii. Analysis of the sodium dodecyl sulfate-polycarylamide gel electrophoresis profiles of strains revealed four groups based on the position of a major protein band (one of the groups showed some heterogeneity and was subdivided into four subgroups). Pulsed-field gel electrophoresis revealed five distinct patterns.

Borrelia↗