Elevated cholesterol. A nurse's guide to drug therapy.
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Anticholesteremic Agents↗
Biomedical subjects
P Howard
Publications and source records attributed to P Howard.
Two years treatment with almitrine bismesylate in patients with hypoxic chronic obstructive airways disease.
Eighty nine patients with hypoxic chronic obstructive airways disease (COAD) were enrolled into the 1 year Vectarion International Multicentre Study-VIMS in 4 centres, Sheffield (UK), and Antwerp, Liege and Namur (Belgium). At the end of the year the remainder were invited to continue taking placebo or almitrine bismesylate (100-200 mg daily) in the same double blind manner for a further 12 months. In the almitrine treated patients mean arterial oxygen tension (Pao2) at the end of the treatment period improved from 7.5 (0.5) kPa to 8.2 (1.3) kPa (p less than 0.01) and arterial carbon dioxide tension (Paco2) fell from 6.1 (0.8) kPa to 5.8 (0.9) kPa (p less than 0.01). Forced expiratory volume in one second (FEV1), forced vital capacity (FVC) and measurements of breathlessness were unchanged. In the placebo treated group changes in the above variables were not significant. Twenty nine patients withdrew from the almitrine group with seven deaths and six cases of peripheral neuropathy, and 22 patients withdrew from the placebo group with six deaths and two cases of peripheral neuropathy. Death rates between the groups were not significantly different. In conclusion, 2 yrs of almitrine treatment (100-200 mg daily) leads to a persistent slight improvement in PaO2 and PaCO2 but no benefit in survival was demonstrated. Patients in this study had a high incidence of drug related side-effects. Lower dose schedules should be investigated.
Almitrine↗
Acute effects of external negative pressure ventilation in chronic obstructive pulmonary disease compared with normal subjects.
This study compares the acute physiological effects of external negative pressure ventilation (ENPV) in normal subjects and patients with chronic obstructive pulmonary disease (COPD). The equipment consisted of an airtight jacket (Pneumosuit) and vacuum pump. Minute ventilation (Ve) was recorded using a light-emitting turbine transducer. Oxygen uptake (VO2) and carbon dioxide output (VCO2) were calculated every 30 s. Measurements were made at rest and during ENPV with pressures of -20 cmH2O and -40 cmH2O. The ventilator rate was fixed at 16.min-1. In 10 normal subjects, Ve increased from 8.6 to 22.9 l.min-1 (p less than 0.01) accompanied by an increase in VCO2 from 0.25 to 0.39 l.min-1 (p less than 0.01). In 10 normocapnic COPD patients (arterial carbon dioxide tension (PaCO2) less than 6.0 kPa) Ve increased from 11.5 to 17.1 l.min-1 (p less than 0.01) whilst in 10 hypercapnic patients (PaCO2 greater than 6.0 kPa) Ve increased from 9.7 to 12.4 l.min-1 (p less than 0.01). A change in VCO2 was not detected in the COPD patients, and VO2 did not change in any group. Arterial blood samples were obtained in eight hypercapnic patients. Baseline mean physiological deadspace ventilation (VD) was calculated to be 4.9 l.min-1 (56% of Ve) whilst Ve was 8.8 l.min-1 in this subgroup. During ENPV, arterial oxygen tension (PaO2) increased from 6.8 to 8.2 kPa (p less than 0.01) whilst PaCO2 decreased from 6.8 to 5.8 kPa (p less than 0.01) suggesting that despite the large physiological deadspace, a significant increase in alveolar ventilation had occurred. In advanced COPD, thoracic compliance falls and limits the ventilatory response to ENPV.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
DNA sequences required for expression of the LH beta promoter in primary cultures of rat pituitary cells.
To begin analysis of the DNA sequences necessary for luteinizing hormone (LH) gene transcription, fusion genes containing the 5' flanking region of the rat LH beta or the human alpha-subunit gene linked to luciferase were transfected into primary cultures of rat pituitary cells. The LH beta-luciferase construct was expressed in the primary cultures at a level 50 times greater than a promoterless luciferase control plasmid. Little or no expression of the LH beta-luciferase construct was detected following transfection of MCF-7, JAR or GH3 tumor cell lines. Treatment of transfected cells with gonadotropin-releasing hormone resulted in a modest induction of LH beta-luciferase activity. Considerably higher levels of LH beta-luciferase activity were obtained with cultures from ovariectomized rats than were obtained with cultures from intact female rats. Analysis of 5' deletions of the LH beta-luciferase construct demonstrated that activity was well maintained even after substantial deletions. The shortest construct, which contained 75 base pairs of 5' flanking sequence had 38% of the activity of the longest which contained 1.7 kilobase pairs of flanking sequence. These findings demonstrate that transfection of primary cultures of rat pituitary cells may provide a useful system for analysis of the cis-acting sequences and trans-acting factors required for LH gene expression.
Animals↗
Post-transcriptional regulation of cAMP-dependent protein kinase activity by cAMP in GH3 pituitary tumor cells. Evidence for increased degradation of catalytic subunit in the presence of cAMP.
The effects of cyclic AMP treatment on total cAMP-dependent protein kinase activity in GH3 pituitary tumor cells have been studied. Incubation of cells for 24 h with 1 microM forskolin resulted in a 50% decrease in total cAMP-dependent protein kinase activity which was reversible upon removal of forskolin from culture media. A similar response was observed in GH3 cells treated with 5 ng/ml cholera toxin and 0.5 mM dibutyryl cAMP but not 0.5 mM dibutyryl cGMP. Northern blot analysis demonstrated that the steady-state level of the mRNA for each of the six kinase subunit isoforms studied was not detectably altered after treatment with 1 microM forskolin for 24 h. The concentration of catalytic subunit was also assessed by binding studies using a radiolabeled heat-stable protein kinase inhibitor. Treatment of GH3 cells with 1 microM forskolin for 24 h reduced protein kinase inhibitor binding activity by 50%, consistent with the observed forskolin-induced decrease in total kinase activity. Analysis of endogenous heat-stable protein kinase inhibitor activity in GH3 cell extracts showed no significant difference between forskolin-treated cells and cells maintained under control conditions. To assess possible effects on catalytic subunit degradation, pulse-chase experiments were performed and radiolabeled catalytic subunit was isolated by affinity chromatography. The results demonstrated that treatment of cells with chlorophenylthio-cAMP detectably increased the apparent degradation of radiolabeled catalytic subunit. The increased degradation of the catalytic subunit was sufficient to account for the observed decreases in kinase activity. These results suggest that relatively long term cAMP treatment can alter total cAMP-dependent protein kinase activity through effects to alter the degradation of the catalytic subunit of the enzyme.
Animals↗
Natural history of obstructive airways disease and hypoxia: implications for therapy.
Chronic irreversible obstructive airways disease (COAD) is the end result of a number of disorders: airway damage from tobacco smoke, atmospheric pollution and occupational dust and fume, bronchiectasis, cystic fibrosis, bronchial asthma and a number of congenital disorders of defective airway defence. The clinical features include sputum, wheeze, breathlessness and infective and noninfective airway inflammation. The pathological consequences are airways obstruction, emphysema and respiratory failure. Except in bronchiectasis, the volume of daily sputum and bronchial infection is less than 20-30 years ago. At autopsy, bronchial gland hypertrophy is now an inconstant feature. Bronchial infection probably contributes little to airways obstruction, but the load of activated neutrophils in bronchiectasis is an important feature. Wheeze comes late to many patients with COAD. It is associated with less reversibility to bronchodilator drugs and more fixed airways obstruction compared to the conventional asthmatic and is probably of different aetiology. Breathlessness is of variable severity when the forced expiratory volume (FEV1) falls below 1.0 liters resulting in disability ranging from manageable to severe. The FEV1 declines an average by 70-80 ml/year (normal approx. 25 ml/year) until the value falls below 1.0 liters, then the rate of decline slows to a plateau which can persist for several years. During this period, hyperinflation, breathlessness and respiratory failure continue to worsen. Significant respiratory failure may be a terminal event or be present for many years. Arterial oxygen tension (PaO2) slowly declines in most patients--"pink puffers" generally have a minimal rate of fall until weeks or months before death, "blue bloaters," by contrast, several times as great.(ABSTRACT TRUNCATED AT 250 WORDS)
Aged↗
Characteristics of children and adolescents in a psychiatric hospital and a corrections facility.
Popular opinion holds that youngsters in corrections programs are delinquents in need of reform, whereas youngsters in psychiatric settings have mental health problems and need therapy. Yet some literature suggests that youth in the two settings may not differ greatly in their mental health status. The authors compared demographic, emotional, and behavioral characteristics of youngsters placed in public psychiatric hospital and corrections settings, and they found few differences. Child Behavior Checklist scores for social competence and total problems were high and quite similar for youngsters in the two settings. White children scored significantly worse than black children on Child Behavior Checklist Internalizing, Externalizing, and total problems in corrections settings but not in the psychiatric hospital. Moreover, race was the only variable that predicted the site in which youth were placed. The findings suggest a need to study (1) the mental health needs of youngsters in nonmental health settings and (2) the procedures by which youth are assigned to service settings.
Adolescent↗
Almitrine bismesylate and oxygen therapy in hypoxic cor pulmonale.
The effect of oral treatment with the thiazine derivative almitrine bismesylate was studied in 28 patients with chronic obstructive pulmonary disease and arterial hypoxaemia receiving long term domiciliary oxygen therapy in a placebo controlled, double blind crossover trial. The initial treatment was given for three months and the second for two months. Because almitrine had an unexpectedly prolonged washout effect crossover analysis could not be performed; data from the placebo treatment administered in the second arm of the trial were used to calculate the half life of almitrine. Nine patients were withdrawn from the study (5 almitrine, 4 placebo). Patients' tolerance of the drug was good. The estimated plasma half life of almitrine was 20.5 days, considerably longer than previously reported. Almitrine caused a significant improvement in arterial oxygen tension (PaO2) with a mean maximum increase of 0.7 kPa at a plasma concentration of 500 ng/ml. Higher plasma concentrations were not associated with any further increase in PaO2. There was no significant effect on arterial carbon dioxide tension (PaCO2). In a second, acute study at the end of each arm of the chronic trial nine patients were subjected to increasing oxygen delivery rates (2, 4, and 6 l/min) for 90 minutes or until blood gas concentrations plateaued. Almitrine increased PaO2 in a dose dependent fashion at all delivery rates, but the effect diminished as PaO2 approached normoxic levels. There was no significant effect on PaCO2. Almitrine treatment results in a significant improvement in PaO2 over that achieved by oxygen alone, an effect that diminishes at high flow rates. Whether this is of clinical benefit is not known. In view of the prolonged half life revised dosage schedules are required.
Almitrine↗
Long term domiciliary oxygen treatment for chronic respiratory failure reviewed.
The use of long term domiciliary oxygen therapy in the Sheffield area from June to August 1987 has been surveyed. Of the 74 patients prescribed long term domiciliary oxygen therapy, 64 were visited at home. These had arterial blood gas tensions or oxygen saturation measured (while breathing oxygen and air), and the indications for long term domiciliary oxygen therapy were examined retrospectively. Fifty two patients had chronic bronchitis and emphysema, the remainder having pneumoconiosis, bronchiectasis, fibrosing alveolitis, and congestive cardiac failure. Of the 54 cases where indications for treatment could be compared with the Department of Health and Social Security (DHSS) guidelines, only 23 (43%) met the full DHSS criteria before the start of treatment. The median length of treatment was 16 months. At follow up 51 patients had an arterial oxygen tension (PaO2) greater than 8.0 kPa when breathing oxygen. They had a significantly higher PaO2 when breathing air than before long term oxygen therapy (6.7 (SD 1.2) kPa before oxygen treatment, 7.6 (1.4) kPa on reassessment). A similar change was seen in the 23 patients assessed as recommended by the DHSS (6.1 (0.8) kPa; 7.2 (1.2]. PaO2 during the breathing of air was less than 7.3 kPa at reassessment in only 21 (33%) patients. Thirteen patients had carboxyhaemoglobin concentrations above 2.5%, the 95th centile of the distribution in nonsmokers in the laboratory.
Aged↗
Evaluation of a turbine flow meter (Ventilometer Mark 2) in the measurement of ventilation.
We have evaluated a turbine flow meter (Ventilometer Mark 2, PK Morgan, Kent, UK) at low flow rates and levels of ventilation which are likely to be encountered during exercise in patients with chronic respiratory disease. Pulsatile flows were generated from a volume-cycled mechanical ventilator, the flow wave-form was modified by damping to simulate a human breathing pattern. Comparative measurements of ventilation were made whilst varying tidal volume (VT) from 0.22 to 1.131 and respiratory rate (fR) from 10 to 35 min-1. At lower levels of ventilation the instrument tended to underread especially with increasing fR. The calibration factor must be adjusted to match the level of ventilation if the measurement errors are to be within 5%.
Calibration↗
From alveoli back to bronchi: new perspectives of bronchoalveolar lavage.
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Asthma↗
Heparin therapy for pregnant women with lupus anticoagulant or anticardiolipin antibodies.
Maternal lupus anticoagulants and anticardiolipin antibodies are associated with a syndrome of recurrent pregnancy loss or preterm birth in live-borns, fetal growth retardation, and placental infarction. Fourteen women with one or more abnormal pregnancy outcomes (total 28 losses, one severely growth-retarded premature live-born) and no normal outcomes were treated with full-dose, subcutaneous, twice-daily heparin therapy in subsequent pregnancies. Treatment was started at an estimated gestational age of 10.3 +/- 4.0 (mean +/- SD) weeks (range 6-18), in a mean total daily dosage of 24,700 +/- 7400 units (range 10,000-36,000). Fourteen of 15 pregnancies resulted in live births at 36.1 +/- 1.7 weeks (range 33-39). The mean birth weight percentile was 57 +/- 21 (range 10-90), and Apgar scores were good to excellent. The number of placental infarcts was fewer in treated cases than in previous deliveries. Five fetuses had third-trimester or perinatal problems with no sequelae, four discovered by close maternal-fetal monitoring. There was an increased rate of preterm and cesarean deliveries. Maternal complications of treatment were few and minor, with no hypertension, preeclampsia, or serious drug-related complications. Heparin appears suitable for further investigation in the treatment of this obstetric syndrome.
Abortion, Spontaneous↗
New thoughts on long term domiciliary oxygen therapy.
The establishment of long term oxygen therapy (LTOT) in the patients' home for chronic respiratory failure associated with obstructive airways disease, is reviewed. The numbers of patients treated in different countries varies widely due to the acceptance of additional physiological criteria to basic measurements of arterial blood gases. The inclusion of these additional criteria has not yet been shown to result in prolonged survival or confer other clinical benefit. Further research studies should be undertaken before they are added to therapeutic guidelines. The selection of patients for home care is still the most difficult problem. It is probably best achieved by a panel of experts to include the local General Practitioner. The most cost effective oxygen administration system is still the oxygen concentrator. Longer term follow up of LTOT has demonstrated a limited survival benefit of approximately five years. It seems that hypoxaemia is being adequately treated but airway disease continues to increase and is eventually responsible for the death of the patient. It was once hoped that oxygen treatment would arrest progress of the disease. As this is not so, further treatments must be sought in addition to oxygen which will deal with progressive airways obstruction. There is a continuing need for research and audit of oxygen therapy particularly in the home environment.
Chronic Disease↗
Enhanced reactivity to bradykinin, angiotensin I and the effect of captopril in the pulmonary vasculature of chronically hypoxic rats.
We compared the reactivity of pulmonary vessels to bradykinin (BK) and angiotensin I (AI) in normal and chronically hypoxic rats; the latter have pulmonary hypertension and muscularized pulmonary arterioles. These peptides are respectively inactivated and activated by the angiotensin converting-enzyme (ACE) on pulmonary endothelium. Isolated lungs were perfused at a constant flow rate when changes in pulmonary artery pressure (Ppa) reflect changes in vascular resistance. Dose-response curves to BK (1 ng-10 micrograms) were derived during normoxia and pre-constriction by hypoxia; BK both decreased and increased vascular resistance, i.e. vasodilation and vasoconstriction. In normal rats only constriction was seen in normoxia, which reflected low basal vascular tone, whereas in chronically hypoxic rats there was only dilatation which reflected high basal vascular tone. In hypoxia in normal rats, low doses caused dilatation, high doses constriction; in chronically hypoxic rats there was again only dilatation which was larger than in controls. After the ACE-inhibitor captopril, constriction was exaggerated in control rats in both normoxia and hypoxia and took place in chronically hypoxic rats after high doses in both normoxia and hypoxia; oedema often followed. Dose-response curves to AI (1 ng-micrograms) in normoxia showed greatly enhanced pressor responses in chronically hypoxic compared with normal rats, probably attributable to increased sensitivity to angiotensin II (AII) rather than enhanced conversion of AI to AII. Captopril caused a proportionate reduction in responses in both groups of rats.(ABSTRACT TRUNCATED AT 250 WORDS)
Angiotensin I↗
Devices for low flow O2 administration.
Long-term oxygen therapy requires a practical regulated oxygen delivery system which works in the home. Although face-masks are cheap and efficient, they are awkward and need removal for talking and eating. Few patients would comply with this for 15 h her day. Nasal prongs are reliable, cheap, safe and well tolerated but are wasteful of oxygen. This waste is important both practically and financially when oxygen is supplied from portable or large cylinders or from a liquid source. The Oxymizer pendants and moustache or inspiration phased delivery devices improve nasal prong efficiency. Nasopharyngeal catheters are an alternative but more invasive means of oxygen conservation. Percutaneous transtracheal catheterization is both oxygen efficient and cosmetically acceptable. As it requires an invasive surgical procedure with some serious potential complications its use should probably be reserved for those patients in whom adequate oxygenation is not achieved by standard nasal prongs. Its use is rarely justified on merely cosmetic grounds. Permanent tracheostomy is not indicated in most cases of hypoxic chronic obstructive airways disease (COAD). Nasal prongs would seem the most reasonable method of oxygen delivery. Their use with oxygen concentrators lessens the need for oxygen conservation.
Catheters, Indwelling↗
Clinical usefulness of bronchoalveolar lavage.
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Bronchoalveolar Lavage Fluid↗
Chromosome 1 studies in Wilms' tumor.
Ten newly diagnosed patients with Wilms' tumor had blood and tumor samples taken for cytogenetic analysis. DNA was also extracted from these samples, along with blood obtained from both parents and an age- and sex-matched control. Molecular biological techniques were employed to study changes present in these samples with respect to chromosome 1. Two DNA probes, PIB 174 and PFBl, mapping to 1q12-qter and 1p12-pter, respectively, were examined for the presence of restriction fragment length polymorphisms (RFLPs) and to detect copy numbers of sequences homologous to the probes. These were normalized with respect to themselves and with regard to a control probe P30. No RFLPs were found with the restriction enzymes used. However, seven patients showed a marked alteration in hybridization signal in tumor and/or blood samples compared to control samples and the control probe. This was apparent using probe PFBl, but just failed to reach statistical significance using nonparametric testing. This would suggest that submicroscopic chromosome 1 changes are present more often in Wilms' tumor than previously recognized, and they may play a leading role in the genesis of this tumor.
Blotting, Southern↗
Hypoxia, almitrine, and peripheral neuropathy.
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Almitrine↗