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Biomedical subjects

C A Wright

Publications and source records attributed to C A Wright.

At least 37 records · Page 2Linked to original sources
PubMed1993

Lack of rebound during intermittent transdermal treatment with glyceryl trinitrate in patients with stable angina on background beta blocker.

OBJECTIVE: To assess whether intermittent transdermal treatment with glyceryl trinitrate causes clinically significant rebound in patients maintained on beta blockers for stable angina pectoris. DESIGN: Serial treadmill exercise testing in a double blind, randomised, placebo controlled cross over trial. Baseline exercise testing was performed at 0900 and 1100 at visit 1. Transdermal glyceryl trinitrate patches releasing 15 mg/24 h were applied at 2200 the evening before visits 2 and 3, and exercise testing was performed at 0900 the next morning. The patch was removed and replaced with either an identical patch or matching placebo and exercise tests were repeated two hours later. The alternative treatment was given at visit 3. SETTING: Tertiary referral centre. PATIENTS: 14 patients with stable angina pectoris maintained on beta blocker treatment alone. MAIN OUTCOME MEASURES: Time to angina, 1 mm ST segment depression, and total time, together with heart rate, systolic blood pressure, and rate-pressure product. RESULTS: Active treatment improved treadmill performance at 0900 and 1100. Time to angina, time to 1 mm ST segment depression, and total time fell significantly on placebo compared with the 0900 exercise test on active treatment, but were not significantly different to the baseline exercise test either. CONCLUSIONS: Intermittent transdermal treatment with glyceryl trinitrate is not associated with the rebound phenomenon in patients maintained on beta blockers for stable angina pectoris.

Administration, Cutaneous↗
PubMed1993

Recalcitrant vulvodynia. A clinicopathological study.

This study is an analysis of 26 women with burning vulva syndrome. They seldom had frankly abnormal physical findings, and application of acetic acid and colposcopically directed biopsy are therefore mandatory. Histopathological study showed characteristic features of human papillomavirus (HPV) in 20 patients (77%). HPV has been shown to be a cause of vulvar vestibulitis syndrome and was an associated problem in 3 of the 5 patients who had essential or dysaesthetic vulvodynia. The latter is similar to causalgia, with a poor prognosis for resolution. Single patients had the following specific conditions: lichen planus, lichen sclerosus, mature neuroma and chronic candidiasis. The study shows that vulvodynia is a multifactorial problem for which management strategies have evolved over the course of time. Although interferon-alpha-2b offers much promise for the treatment of vulvodynia caused by subclinical HPV infection, the complete cure rate was only 58%. Overall 38% of patients still experience their problem, which indicates that they should be discouraged from going from physician to physician in the hopes of finding a 'cure'.

Adolescent↗
PubMed1991

Three dimensional closed loop control of the human circulation.

In the control of the circulation it is suggested there is merit in describing states which are the object of each therapy. Considering the determinants of venous return rather than those of cardiac output, we suggest that the mean systemic filling pressure is a parsimonious description of the volume state. A method is described of deriving a mean systemic filling pressure analogue based on stopping the flow in a notional regional systemic circulation. The mean systemic filling pressure (PM) forms a quantitative link between volume therapy and circulatory dynamics. The systemic vascular resistance is a conventional measure of the state of arteriolar resistance. We suggest that the ratio (PM - PRA)/PM (where PRA is the right atrial pressure) is a global measure of the effect of cardioactive drugs. Studies are reported in which the mean blood pressure, right atrial pressure and cardiac output are simultaneously controlled within desired tolerances using state based control.

Blood Circulation↗
PubMed1990

The start of breast development and age at menarche in South African black females.

Age at the start of breast development and at menarche are important maturity indicators in adolescent females. Breast development is usually the first event of puberty and menarche virtually the last. Irregularities in the age of the subject at their appearance can denote a lack of synchronisation between pubertal events, which, in turn, may indicate hormonal or psychosocial disturbance. Data are presented on the age of occurrence of breast development, according to Tanner's criteria, and age at menarche for urban and rural South African black females. In addition published reports are reviewed to determine whether there is a pattern of change in these ages. Breast development seems to be fairly stable, occurring in girls between the ages of 10.5 years and 11.5 years. Age at menarche appears to have decreased over the last 40 years in children from both urban and rural environments. Girls from rural areas have a delay of about 1.5 years in both pubertal events.

Adolescent↗
PubMed1988

Renal failure and nephrotic syndrome associated with sulindac.

Four elderly patients developed nephrotic syndrome while receiving sulindac. Sulindac treatment had commenced 4-12 months prior to presentation with the nephrotic syndrome. Two patients also developed oliguric renal failure. Renal biopsy in one showed minimal change nephropathy and in three cases membranous nephropathy. Interstitial nephritis was present on renal biopsy in all cases. The nephrotic syndrome and renal failure resolved in all cases after withdrawal of sulindac. Two patients received steroid therapy and improvement in renal function and disappearance of proteinuria seemed to be temporarily related to steroid therapy in both cases. Despite the fact that sulindac is less likely to cause renal failure due to inhibition of renal prostaglandin secretion this report shows that sulindac treatment can be associated with renal failure and the nephrotic syndrome.

Acute Kidney Injury↗
PubMed1986

Characterisation of chicken erythroid nuclear proteins which bind to the nuclease hypersensitive regions upstream of the beta A- and beta H-globin genes.

Chicken erythrocyte sequence-specific nuclear DNA-binding proteins, which bind to the 5'-flanking DNAseI hypersensitive sites of the erythrocyte chromosomal beta A- and beta H-globin genes, have been fractionated by HPLC gel filtration. Three beta A-globin gene DNA binding activities (to sites A, B and B' (10-12)) were separated. The erythroid precursor cell line HD3 has beta A-globin gene sites B and B' binding activities, but binding to site A is detected only after the HD3 cells are induced to differentiate. The fractionated protein binds to a redefined site B', which contains at its center the globin CACCC consensus sequence. The chromosomal beta H-globin gene has two 5'-flanking DNAseI hypersensitive sites which bracket two sequences (H and H') bound by erythrocyte and HD3 nuclear protein in vitro. The beta H- and beta A-globin gene binding sites (H and B) contain variants of the sequences bound by Nuclear Factor 1 and the TGGCA-binding protein, and their protein binding activity(ies) co-purify after HPLC gel filtration.

Animals↗
PubMed1986

Sequence-specific DNA-binding proteins which interact with (G + C)-rich sequences flanking the chicken c-myc gene.

The interaction of nuclear sequence-specific DNA-binding proteins from definitive chicken erythrocytes, thymus and proliferating transformed erythroid precursor (HD3) cells with the 700-base-pair (700-bp) DNA 5'-flanking region of the chicken c-myc gene was investigated by in vitro footprint analysis. The major HD3 protein-binding activity binds to a site (site V) 200 bp upstream from the 'cap' site but, after further fractionation, a second distinct binding activity is detected to a site (site VIII) which contains both the 'CAAT' and 'SP1-binding' consensus sequences. Protein from thymus and erythrocyte cells which express c-myc at lower levels, bind to seven and eight sites respectively. In common with HD3 cell protein, they both bind to site VIII and, although binding to the sequence at site V is also detected, the footprint protection pattern is sufficiently different (site V') to suggest the involvement of different proteins in terminally differentiated and proliferating cells. The DNA-binding activities were partially fractionated by high-performance liquid chromatography gel filtration and include an erythrocyte-specific protein which binds to a c-myc gene poly(dG) homopolymer sequence similar to that found upstream of the chicken beta A-globin gene.

Animals↗
PubMed1986

Value of the bipolar lead CM5 in electrocardiography.

Only bipolar lead recording are available during ambulatory monitoring. Their sensitivity in detecting ST segment changes in relation to standard electrocardiographic leads is not known. The magnitude and direction of ST segment changes in the bipolar lead CM5 were compared with those in standard electrocardiographic leads in patients during exercise testing and percutaneous transluminal coronary angioplasty. Thirty patients with coronary artery disease were studied during exercise tests in which ST segment depression (greater than 0.5 mm) occurred in one or more standard electrocardiographic leads and 13 patients were studied during angioplasty that resulted in ST segment change in one or more leads (I, II, III, V2, V5, and CM5). Lead CM5 was the most sensitive lead (93%) during exercise testing and also showed the greatest magnitude of ST segment change below the isoelectric line in 93% of the patients. Only two patients, one with ST segment elevation in inferior leads and one with changes restricted to septal leads, had no ST segment depression in lead CM5. When ST segment shift from the baseline electrocardiogram was measured the magnitude of depression was greatest in lead CM5 in only 63% of the patients. During angioplasty of the left anterior descending coronary artery, lead CM5 showed ST segment depression in seven patients, ST segment elevation in two, and a biphasic response in one. Two of the three patients with balloon inflation in right coronary artery developed ST segment elevation in lead CM5. Thus lead CM5 is a reliable lead for detecting subendocardial ischaemia experienced during everyday activities in anginal patients. During total occlusion of coronary arteries (as in variant angina or myocardial infarction) lead CM5 commonly shows ST segment depression and changes due to right coronary artery occlusion may not be detected.

Coronary Disease↗
PubMed1985

Multiple sequence-specific DNA binding activities are eluted from chicken nuclei at low ionic strengths.

DNA sequence-specific binding proteins eluted from chicken erythrocyte and thymus nuclei, and fractionated as described by Emerson and Felsenfeld (19), have been investigated by filter binding and footprint analyses. The erythrocyte nuclear protein fraction specifically binds to at least two sites within the 5' flanking chromatin hypersensitive site of the chicken beta A-globin gene, and to a site 5' to the human beta-globin gene. The major chicken beta A globin gene binding site [G)18CGGGTGG) and the human beta-globin gene binding site [TA)6(T)8C(T)4) occur at or near sequences which are hypersensitive to S1 nuclease cleavage in supercoiled plasmids. Downstream, the second chicken beta A-globin gene binding site includes the beta-globin gene CACCC consensus sequence. Filter binding studies also show other sequence specific binding activities to human N-ras and human (but not chicken) c-myc gene sequences.

Animals↗
PubMed1985

The effect of salt extraction on the structure of transcriptionally active genes; evidence for a DNAseI-sensitive structure which could be dependent on chromatin structure at levels higher than the 30 nm fibre.

The procedure developed by Lawson and Cole (Biochemistry, 1979, 18 2161-2166) for removing lysine-rich histones from nuclei at low pH also quantitatively extracts proteins HMG14 and 17. The effect of this low pH extraction on the DNAseI-sensitive structures of active genes in avian red blood cells has been investigated. No major perturbation of a developmentally regulated DNAseI hypersensitive site in the beta-globin domain and at the 5' end of the alpha D gene was seen. The overall DNAseI-sensitive conformation of the beta A-globin gene (relative to the ovalbumin gene) is minimally affected by pH3 salt extraction, but there is some loss of sensitivity of the alpha D gene. Removal of HMG proteins at neutral pH had no effect on the sensitivity of active genes in erythroid or fibroblast nuclei. These results, together with those carried out on DNAseI sensitivity and HMG binding to monomer nucleosomes, indicate that there is a major structural feature of active genes responsible for DNAseI-sensitivity which is independent of HMG proteins or nucleosome core particle structure but may be dependent on higher order chromatin structures.

Animals↗
PubMed1985

Fractionation by high-performance liquid chromatography of the low-molecular-mass high-mobility-group (HMG) chromosomal proteins present in proliferating rat cells and an investigation of the HMG proteins present in virus transformed cells.

The low-molecular-mass high-mobility-group (HMG) proteins from young rat thymus nuclei were fractionated by high-performance liquid chromatography. Two proteins analogous to calf HMG14 and HMG17 were found together with a third major component HMGI similar to that found in HeLa cells [Lund et al. (1983) FEBS Lett. 152, 163-167]. HMGI has as amino acid composition similar to but distinct from HMG14 and HMG17. The three proteins form a family of proteins with HMG14 having an amino acid composition intermediate between HMG17 and HMGI. HMGI is present in proliferating fibroblasts and embryos but is present in very low levels in rat liver, a non-dividing tissue, supporting the notion that HMGI is required for proliferating cells. Fibroblasts transformed with avian sarcoma virus have high levels of HMGI and an additional band HMGI' but the presence of HMGI and HMGI' is not dependent on a functional src gene product.

Amino Acids↗
PubMed1985

Effects of myocardial revascularisation in patients with effort angina and those with effort and nocturnal angina.

The effects of coronary artery bypass graft operation were studied in 32 patients with daytime ambulatory ST segment changes and 14 patients with daytime and nocturnal angina and ST segment changes. Patients had ambulatory ST segment monitoring and exercise testing before and after operation and coronary arteriography was repeated in 34 patients after operation. Before operation, patients with daytime and nocturnal ischaemia tended to have more severe coronary artery disease, lower exercise tolerance, and more frequent ambulatory ST segment changes than those who had daytime ST segment changes only. After operation chest pain recurred in 22% of patients and ST segment depression during exercise testing or ambulatory ST segment monitoring recurred in 37% of the patients and was significantly more frequent in those with nocturnal ischaemia than in those with daytime ischaemia. Graft patency rates were similar in patients with and those without recurrence of ischaemia. After operation the frequency and magnitude of ST segment changes and exercise duration were improved in patients with preoperative daytime angina and also in those with daytime and nocturnal angina. The improvement was more pronounced in the latter groups. Thus, absence of postoperative angina is not a reliable indicator of the absence of reversible myocardial ischaemia. After revascularisation, patients with rest and nocturnal angina can expect relief from ischaemia, and if this recurs postoperatively, the threshold is improved and pain usually occurs only on exertion.

Angina Pectoris↗
PubMed1984

Mechanisms of nocturnal angina pectoris: importance of increased myocardial oxygen demand in patients with severe coronary artery disease.

Changes in heart rate before and throughout episodes of ST-segment depression were recorded during ambulatory electrocardiographic monitoring in five patients with daytime and nocturnal resting angina and six patients with daytime angina only, who all had severe obstructive coronary disease. In 16 of 17 nocturnal episodes and in all the daytime episodes the heart rate increased before the onset of ST-segment depression. There were no significant differences in the sequence and magnitude of changes in daytime, nocturnal, painful, or painless episodes. The maximum heart rate during individual episodes preceded the maximum ST-segment depression by a mean 80.7 s and in the majority of episodes the heart rate returned to baseline before the ST segment. Thus, in severe coronary artery disease the mechanisms producing nocturnal resting ischaemia were apparently similar to those during daytime exertion; increased myocardial oxygen demand not coronary spasm seemed responsible for most of the episodes of nocturnal ischaemia.

Aged↗
PubMed1984

Comparative efficacies of mezlocillin and ampicillin alone or in combination with gentamicin in the treatment of Streptococcus faecalis endocarditis in rabbits.

The in vitro and in vivo activities of mezlocillin and ampicillin, alone and in combination with gentamicin, against Streptococcus faecalis were compared. In vitro, relative bactericidal and activities for 10 strains of S. faecalis were as follows: mezlocillin plus gentamicin greater than ampicillin plus gentamicin (P is not significant) greater than mezlocillin (P less than 0.01) greater than ampicillin (P less than 0.01) greater than gentamicin (P less than 0.01) greater than control (P less than 0.01). One of the strains was used to induce endocarditis in rabbits. Infected rabbits were treated by random selection with ampicillin, mezlocillin, ampicillin plus gentamicin, mezlocillin plus gentamicin, or saline (control) for 7 days. Among antibiotic-treated rabbits, survival rates were the same, but ampicillin was less effective than the other regimens in sterilizing both blood cultures (P less than 0.001 on day 4) and cardiac vegetations (P less than 0.05 on day 7). Differences in quantitative vegetation cultures among rabbits treated with mezlocillin, mezlocillin plus gentamicin, or ampicillin plus gentamicin and sacrificed on day 7 were not significantly different. Peak inhibitory and bactericidal antibacterial activity titers in serum determined during treatment were higher with mezlocillin (with or without gentamicin) than with ampicillin (with or without gentamicin) (P less than 0.01). Mezlocillin may be more effective than ampicillin in the treatment of S. faecalis infections in humans.

Ampicillin↗
PubMed1983

The nuclease sensitivity of active genes.

Brief micrococcal nuclease digestion of chick embryonic red blood cells results in preferential excision and solubilization of monomer nucleosomes associated with beta-globin sequences and also 5'-sequences flanking the beta-globin gene. Both regions are DNAse-I sensitive in nuclei. Such salt-soluble nucleosomes are enriched in all four major HMG proteins but HMG1 and 2 are only weakly associated. These nucleosomes appear to have lost much of the DNAse-I sensitivity of active genes. The HMG14 and 17-containing salt-soluble nucleosomes separated by electrophoresis are not DNAse-I sensitive and contain inactive gene sequences as well as active sequences. Reconstitution of HMG proteins onto bulk nucleosomes or chromatin failed to reveal an HMG-dependent sensitivity of active genes as assayed by dot-blot hybridization and it was found that the DNAse-I sensitivity of ASV proviral sequences as assayed by dot-blot hybridization was not HMG-dependent. These results indicate that higher order chromatin structures might be responsible for nuclease sensitivity of active genes.

Animals↗