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Biomedical subjects

C J Clark

Publications and source records attributed to C J Clark.

At least 37 records · Page 2Linked to original sources
PubMed1996

Low intensity peripheral muscle conditioning improves exercise tolerance and breathlessness in COPD.

This randomized, controlled study investigated the physiological effects of a specially designed 12 week programme of isolated conditioning of peripheral skeletal muscle groups. The programme required minimal infrastructure in order to allow continued rehabilitation at home after familiarization within hospital. Forty eight patients, aged 40-72 yrs with chronic obstructive pulmonary disease (COPD) (mean (SD) forced expiratory volume in one second (FEV1) 61 (27)% of predicted normal) were randomly allocated into training (n = 32) and control (n = 16) groups. Physiological assessments were performed before and after the 12 week study period, and included peripheral muscle endurance and strength, whole body endurance, maximal exercise capacity (maximum oxygen consumption (V'O2,max)) and lung function. The training group showed significant improvement in a variety of measures of upper and lower peripheral muscle performance, with no additional breathlessness. Whole body endurance measured by free arm treadmill walking increased by 6,372 (3,932-8,812) 3 (p < 0.001). Symptom-limited maximal V'O2 was unchanged. However, the training group showed a reduction in ventilatory equivalents for oxygen and carbon dioxide, both at peak exercise and at equivalent work rate (Wmax). In summary, low intensity isolated peripheral muscle conditioning is well-tolerated, simple and easy to perform at home. The various physiological benefits should enable patients across the range of severity of chronic obstructive pulmonary disease to improve daily functioning.

Exercise↗
PubMed1995

Efficiency of sampling: birthweight and gestational age distributions in two cohorts, < 31 weeks and 500-1499 grams.

We studied the efficiency of two common sampling strategies used to assemble cohorts to study the long-term problems of preterm infants: infants with birthweights of 500-1499 g, and infants with gestational ages (GA) of < 31 weeks. Birthweight, GA and 2-year outcome data from a population based study of infants < 2001 g, the Central New Jersey Brain Hemorrhage Study (NBH), were used to define the birthweight and GA distributions, at enrollment and at the age of 2 years, of overlapping subsets: infants 500-1499 g (n = 599) and infants < 31 weeks of age (n = 522). Using frequencies from the NBH study, we estimated that 1000 infants of 500-1499 g enrolled at birth would produce 712 infants at the age of 2 years, 498 below 31 weeks and 214 above. Enrolling 1000 infants < 31 weeks would produce a cohort of 697 infants at the age of 2, all of whom were < 31 weeks. Neither sampling strategy maximised the statistical power to investigate the pathophysiological determinants of long-term outcomes associated with short GA. Both methods oversampled older GAs. A stratified sampling technique based on GA, designed to produce equal numbers of subjects at each week of GA, would improve statistical power to study long-term outcomes. As we move from descriptive to analytical studies of preterm infants, we need to devise efficient, GA-based, sampling strategies that maximise statistical power to test pathophysiological hypotheses.

Birth Weight↗
PubMed1994

Guanine nucleotide regulatory protein alterations in young Milan hypertensive strain rats.

Vascular smooth muscle cell membranes from prehypertensive rats of the Milan hypertensive strain (MHS) were used to examine adenylyl cyclase activity and its regulation by guanine nucleotide regulatory proteins (G-proteins). Basal adenylyl cyclase activity was similar in MHS and Milan normotensive strain (MNS) membranes. Forskolin (10(-4) M) produced a significantly greater stimulatory response in MHS membranes, but this was not observed with NaF (10(-2) M). Isoproterenol (10(-4) M) caused a significantly decreased stimulation of adenylyl cyclase activity in MHS membranes, while prostaglandin E1 (10(-5) M) produced similar responses in the two strains. Gi function and GTP responses, as observed by biphasic effects of GTP on isoproterenol-stimulated membranes, were similar in both strains. The levels of Gi2 alpha and Gq alpha/G11 alpha were similar in the two strains, while the levels of Gs alpha (44 and 42 kDa forms) and the beta-subunit were significantly reduced by approximately 20% in MHS membranes. The alpha-subunit of Gi3 was dramatically reduced by approximately 80% in MHS membranes. The affinities of beta-adrenergic receptors for the antagonist, cyanopindolol, were similar in the two strains; however, the number of beta-adrenoceptors was substantially reduced in MHS membranes. These findings may be of relevance to altered vascular reactivity and transmembrane ion distribution observed in the MHS.

Adenylyl Cyclases↗
PubMed1994

Use of static and dynamic NMR microscopy to investigate the origins of contrast in images of biological tissues.

NMR imaging experiments have been carried out on a fruit (Actinidia deliciosa) and plant stem (Stachys sylvatica) using a wide range of image contrasts. These included T1, T2, T2*, diffusion, flow and chemical shift selection. In the case of fruit imaging we calculated relaxation time and diffusion maps and established that the imaged parameters varied significantly with fruit ripening. These changes we attribute to changes in water dynamics resulting from elevated sugar concentrations. For the plant stem, water flow has been observed in the xylem vessels with a maximum velocity of 70 microns s-1. The role of image artifacts is considered and, in the case of transverse relaxation, we have demonstrated that it is necessary to use a precursor Carr-Purcell-Meiboom-Gill pulse train if additional diffusive attenuation is to be avoided.

Fruit↗
PubMed1994

The influence of education on morbidity and mortality in asthma (including the use of open access hospital admission for severe attacks).

Despite the availability of effective drugs, asthma morbidity and mortality are increasing. Undertreatment is a significant contributory factor providing the rationale for improved concentration on education of asthmatics. A review of asthma education programmes reveals improvements in a variety of outcome measures. However, the types of patients studied in these programmes are very variable and it remains an unproven assumption that previously non-compliant and undertreated patients are amenable to improving asthma through education. The problems of compliance are common both in childhood and adult asthma. Further concentration on strategies to improve the management of this particular sub-group require development. In general, education programmes appear more effective when they consist of specific self-management instructions rather than general education regarding the disease process.

Adult↗
PubMed1994

The place of education in the management of chronic lung disease.

Health education, although an interesting logical requirement for management of chronic lung disease, is a complete process. It consists of more than transmission of a message with the expectation of implementation. The core materials can easily be identified, but the patient's response cannot be anticipated. Education of the health care providers, in this context respiratory physicians, regarding the second stage, should help to improve outcome.

Humans↗
PubMed1993

Guanine nucleotide regulatory proteins in the spontaneously hypertensive rat.

We compared guanine nucleotide regulatory protein (G protein) levels and function in plasma membranes from resistance vessels (mesenteric arteries) isolated from spontaneously hypertensive (SHR) and normotensive Wistar rats. G protein function was deduced from studies of adenylate cyclase activity. Although the basal level of adenylate cyclase activity (+/- Mn2+ ions) was significantly greater in SHR membranes, addition of agents that function via the stimulatory G protein--i.e., NaF (10(-2) M), (-)-isoproterenol (10(-4) M), and prostaglandin E1 (10(-5) M)--resulted in a significantly lower stimulatory response in SHR membranes. Ligands that function via the inhibitory G protein--i.e., adrenaline (10(-5) M)/propranolol (10(-5) M) (this combination being equivalent to an alpha 2-receptor agonist), carbachol (10(-3) M), and serotonin (10(-5) M)--were responsible for only slight inhibitory responses in both SHR and Wistar rat membranes, which were not significantly different. Western blotting identified the presence of Gs, Gi2, and Gi3 alpha-subunits in rat vascular smooth muscle, but there were no differences in the levels of these G protein alpha-subunits found in SHR and Wistar rat plasma membranes. The levels of the beta-subunit in the two sets of membranes were also similar. In conclusion, there is a reduced response in adenylate cyclase activity to agents that function via the stimulatory G protein in SHR membranes. However, this is not a consequence of altered levels of the different G protein subunits.

Adenylyl Cyclases↗
PubMed1993

Guanine nucleotide regulatory protein alterations in the Milan hypertensive rat strain.

OBJECTIVE: To examine whether the altered regulation of adenylyl cyclase that has been reported in vascular tissues from spontaneously hypertensive rats is also evident in the Milan hypertensive (MHS) rat strain. DESIGN: The plasma membranes of vascular smooth muscle cells derived from thoracic aortae from adult (60-day-old) MHS and Milan normotensive (MNS) strain rats were studied. METHODS: Guanine nucleotide regulatory protein (G-protein) function was inferred from adenylyl cyclase activity studies, and levels of G-protein subunits were assessed by immunoblotting. beta-Adrenergic receptor number and affinity were measured from the binding of the antagonist [125I]-cyanopindolol. RESULTS: Basal adenylyl cyclase activity was increased significantly in MHS rat cell membranes, and stimulation by 0.1 mmol/l isoproterenol and 0.01 mmol/l prostaglandin E1 was significantly greater in MHS than in MNS rat cell membranes. Forskolin (at 0.1 mmol/l) resulted in a significantly greater stimulatory response in MHS membranes, which was eliminated by 0.01 mol/l NaF. Biphasic effects of GTP on isoproterenol-stimulated membranes demonstrated similar Gi function in MHS and MNS rat cell membranes, although a greater stimulatory GTP response was observed in MHS rat cell membranes. The levels of Gs alpha (both forms), Gi3 alpha and the beta-subunit were reduced in MHS rat cell membranes, whereas the levels of Gi2 alpha and Gq alpha and G11 alpha were unchanged. The number of beta-adrenoceptors was increased significantly in MHS rat cell membranes, whereas receptor affinity for the antagonist was unaltered. CONCLUSIONS: There are differences in adenylyl cyclase stimulatory responses in MHS rat vascular smooth muscle cell membranes. We have found evidence of reduced levels of particular G-protein subunits, altered beta-adrenoceptor-Gs coupling and increased beta-adrenoceptor number.

Adenylyl Cyclases↗
PubMed1992

Guanine nucleotide regulatory protein levels and function in spontaneously hypertensive rat vascular smooth-muscle cells.

We compared G-protein levels and function in membranes from vascular smooth-muscle cells (VSMC) derived from mesenteric arteries from SHR, WKY and Wistar rats. Basal adenylyl cyclase activity was significantly reduced in SHR membranes compared with Wistar, but was similar to WKY. Isoproterenol stimulation (10(-4) M) was significantly lower in SHR membranes compared to WKY, but was similar to that in Wistar, which was also significantly lower than WKY. Forskolin (10(-4) M) and NaF (10(-2) M), resulted in a higher stimulatory response in SHR membranes. Biphasic effects of GTP on isoproterenol-stimulated membranes demonstrated unaltered Gi function in SHR membranes. No significant differences were seen in the levels of Gs alpha (44- and 42-kDa forms), Gi2 alpha and the beta-subunit in immunoblotting studies of the membranes. Amounts of Gq alpha/G11 alpha and Gi3 alpha were also unchanged. In conclusion, there are differences in adenylyl cyclase responses in SHR VSMC membranes which are not a consequence of altered levels of G-proteins, but may reflect genetic differences rather than effects of hypertension.

Adenylyl Cyclases↗
PubMed1992

Benign ovarian cysts in England and Wales and in the United States.

OBJECTIVE: To compare the rates of hospital admission for management of ovarian cysts in England and Wales and the United States between 1972 and 1974 and 1984 and 1986; and to determine whether these rates are related to rates of early diagnosis of ovarian cancer. DESIGN: Analysis of published and unpublished hospital discharge data based on national samples, the Hospital In-patient Enquiry (HIPE), a 10% hospital discharge sample for England and Wales, and the National Hospital Discharge Survey (NHDs), a 5% sample for the United States. MAIN OUTCOME MEASURES: Age-specific discharge rates for primary and secondary diagnoses of ovarian cyst or benign ovarian tumour. RESULTS: There was an age-adjusted increase in discharge rates of about 8% in both countries; discharge rates in the United States were approximately double those in England and Wales in both time periods. There was no difference in the rates of early diagnosis of ovarian cancer. CONCLUSIONS: Ovarian cysts are a common cause of hospital admission in both countries. The higher rates in the United States are not associated with earlier diagnosis of ovarian cancer.

Adult↗
PubMed1992

The role of physical training in asthma.

The wide interpatient and intrapatient variability in asthma severity necessitates an individualized approach to rehabilitation. Objectives of management are first, to determine the exercise capacity of the patient; second, to prescribe specific exercise rehabilitation according to the results of evaluation and illness severity; and third, to provide supervised hospital-based programs for specific subgroups. Disability in asthma is influenced by psychosocial variables, including attitude to exercise, education, social circumstances, and personality. A difference in perceived limitation and actual ability is often present. A 4-quadrant analysis is used to illustrate the interrelation between exercise intensity and the resulting ventilatory response in determining training effect in an individual with asthma. Medically supervised training using these principles can significantly improve "cardiovascular fitness" variables and submaximal ventilatory and metabolic responses. Breathlessness is also decreased over a wide range of work corresponding to activities of daily living. PIE evaluation can be used to determine the choice of rehabilitation program to improve either exercise capacity or alternatively muscle strength and mobility depending on individual capabilities.

Adolescent↗
PubMed1991

Increased airways reactivity after smoke inhalation.

13 fire victims who required treatment after smoke inhalation underwent lung function assessment within 3 days of injury and 3 months later. Initial airways hyperreactivity improved over this period, but FEV1 and airways specific conductance did not change significantly. There was a strong correlation between exposure carboxyhaemoglobin concentration (an indicator of smoke exposure) and initial airways specific conductance (r + 0.79; p = 0.006). Airways obstruction after smoke inhalation in house fires may be more common and more persistent than is generally recognised. Early lung function tests would allow the incidence of pulmonary complications after smoke inhalation and the potential benefits of early use of inhaled antiinflammatory drugs to be assessed.

Adult↗
PubMed1991

Effect of Hydrogen Cyanamide on Amino Acid Profiles in Kiwifruit Buds during Budbreak.

Buds, and resultant shoots, were collected from kiwifruit (Actinidia deliciosa [A. Chev.] CF Liang et AR Ferguson var deliciosa cv Hayward) vines from late autumn until late spring with and without hydrogen cyanamide treatment. Those samples were weighed and analyzed for total nitrogen and free amino acids. By 7 days after hydrogen cyanamide treatment, the amount of proline had risen to nearly one-quarter of the total amino acid pool in the treated buds and that proportion was maintained for at least 14 days before it declined. The maximum concentration detected in treated buds was 25.8 micromoles per gram dry weight, 6.6 times that detected in untreated buds. By 95 days after treatment, the relative amounts of proline were not significantly different.

Journal Article↗
PubMed1990

Changes in alveolar macrophage, monocyte, and neutrophil cell profiles after smoke inhalation injury.

Thirty two fire victims with smoke inhalation, with or without burns, and 26 control subjects had bronchoalveolar lavage performed. Cell yields and differential cell counts were assessed. All patients and controls were cigarette smokers. Patients with smoke inhalation (SI) injury generally showed higher total bronchoalveolar lavage (BAL) cell yields, and this was significant on repeat lavage from 12 patients. The increase was almost entirely due to an increase in the proportion of neutrophils in patients with smoke inhalation alone (S) and those with cutaneous burns as well as smoke inhalation (S + B). On sequential lavage of 12 patients with smoke inhalation (SI) the proportion of neutrophils had increased; this was significantly higher than on initial lavage. Using various macrophage markers, the proportions of macrophage subgroups were determined. There was an increase in UCHM1 and RFD9 positive cells in each subgroup: the increase in UCHM1 positive cells was significant in patients with burns as well as smoke inhalation, and the increase in RFD9 positive cells was significant in patients with smoke inhalation alone. Assessment of the role of such cells in the development of acute lung injury (such as adult respiratory distress syndrome) may be important in our understanding of the mechanisms entailed.

Bronchoalveolar Lavage Fluid↗