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Biomedical subjects

C Hall

Publications and source records attributed to C Hall.

At least 19 recordsLinked to original sources
PubMed1997

The cervical spine in Crouzon syndrome.

STUDY DESIGN: All cervical spine radiographs of 44 patients with Crouzon syndrome treated at Great Ormond Street Hospital during the past 10 years were studied. OBJECTIVES: To assess the incidence and pattern of cervical spine abnormalities of patients with a confirmed diagnosis of Crouzon syndrome, but particularly regarding progressive fusion. SUMMARY OF BACKGROUND DATA: Previous studies into the cervical spine anomalies in those with Crouzon syndrome have shown an increased incidence of congenital abnormalities compared with the normal population. There is some suggestion from previous studies that cervical spine fusions are progressive in nature. METHODS: All radiographs were reviewed by the craniofacial team, along with a single pediatric radiologist with experience in assessment of skeletal dysplasias. RESULTS: Radiologic abnormalities included "butterfly" vertebrae and fusions of the bodies and the posterior elements. Evidence of fusion was present in eight of 44 (18%) of patients. C2-C3 and C5-C6 were almost equally affected. Block fusions involving multiple vertebrae were seen. Analysis of sequential studies in 16 patients showed evidence of progression in five. CONCLUSIONS: These results reveal an incidence of fusions that is lower than reported previously. There is radiologic evidence from serial studies that the fusions are progressive, and because these patients are children, the fusion process may not be complete, which may account for the lower incidence of fusions than in previous studies. The pattern of fusions is different from that in earlier studies, which may be a result of the method of diagnosis because this population is less likely to include atypical forms of other syndromes (which have a higher incidence of cervical fusions, particularly at C2-C3). Regarding other congenital anomalies, it appears that butterfly vertebrae are especially prevalent in association with Crouzon syndrome.

Cervical Vertebrae↗
PubMed1997

Neuroperceptual differences in consonant and vowel discrimination: as revealed by direct cortical electrical interference.

The effects of direct cortical electrical interference on consonant and vowel discrimination were investigated in five patients with implanted subdural electrode arrays. Without electrical interference, patients performance discriminating consonants and vowels was intact. With electrical interference, consonant discrimination was impaired at one electrode site in each patient on the superior temporal gyrus of the lateral left perisylvian cortex. Conversely, vowel and tone discrimination remained relatively intact when tested with electrical interference at the same site. Analysis of patients' consonant discrimination errors revealed that neither differences in acoustic temporal structure nor syllable position fully account for the consonant-vowel perceptual dissociations elicited. Our data suggest that at the cortical level consonant and vowel perception are intrinsically distinct perceptual phenomena. The selective impairment of consonant, but not vowel, discrimination further suggests that consonant and vowel perception are distinguished by differences in relative dependence on the functional--perhaps integrative--resources of the left lateral superior temporal gyrus.

Adolescent↗
PubMed1997

Effects of angiotensin II receptor blockade on N-terminal proatrial natriuretic factor plasma levels in chronic heart failure.

BACKGROUND: Plasma N-terminal proatrial natriuretic factor (N-terminal proANF) has been shown to reflect intraatrial pressures in heart failure patients, and may be used as a biochemical parameter of atrial pressures. It is still unclear how treatment of heart failure influences the relationship between hemodynamic parameters and plasma levels of N-terminal proANF. METHODS AND RESULTS: This double-blind, placebo-controlled study investigated whether 12 weeks of treatment with the angiotensin II receptor blocker losartan influenced N-terminal proANF plasma levels in 129 chronic heart failure patients. After 12 weeks of treatment, N-terminal proANF level was increased in patients given placebo by 344 +/- 1126 pmol/L, whereas in patients given 50 mg losartan, the levels had decreased by 251 +/- 886 pmol/L (P < .01 vs placebo). The change in N-terminal proANF correlated significantly with the corresponding change in pulmonary capillary wedge pressure (r = .53, P < .001). CONCLUSION: The correlation between N-terminal proANF plasma levels and pulmonary capillary wedge pressure at baseline, as well as the correlation between the changes in these parameters during treatment, suggests that plasma N-terminal proANF may be used to monitor effects on left ventricular filling pressures in patients treated with losartan.

Aged↗
PubMed1997

Plasma N-terminal atrial natriuretic factor: a predictor of survival in patients with congestive heart failure.

BACKGROUND: Congestive heart failure results in biatrial stretch, which stimulates myocyte release of atrial natriuretic factor (1-126). The N-terminal fragment, proatrial natriuretic factor(1-98), (proANF), is released on an equimolar basis with the C-terminal (99-126) active hormone and may be assayed simply because of prolonged in vitro stability. Proatrial natriuretic factor has been shown to be predictive of clinical status in patients with congestive heart failure. This retrospective analysis was undertaken to evaluate the relationship between N-terminal atrial natriuretic factor(1-98) and survival in patients with stable congestive heart failure. METHODS AND RESULTS: Proatrial natriuretic factor was sampled from 316 patients (mean age, 68 (+/-) 11 years; 71% men) recruited from an outpatient heart failure clinic. The mean ejection fraction was 34 (+/-) 13%. Seventy-three deaths were registered during the period of data collection (42 months). Deaths per proANF quartile (n = 79) were as follows: 2 (2.5%) in quartile I. 13 (16.5%) in quartile II, 21 (26.6%) in quartile III, and 37 (46.8%) in quartile IV. The odds ratio estimates for death adjusted for age and sex were 7.6, 13.9, and 33.9 for the second, third, and fourth quartiles, respectively. Survival curves constructed according to proANF quartiles demonstrate significant differences in mortality rates. The correlation with death was greater for proANF as compared with left ventricular end-diastolic diameter (P < .001), systolic pulmonary artery pressure (P < .005), or ejection fraction (P < .05). CONCLUSION: These data indicate that the concentration of proANF is related to prognosis in patients with heart failure and that moderate elevation is associated with markedly decreased survival. Analysis should be of practical value in the assessment of prognosis in this heterogeneous population.

Adolescent↗
PubMed1997

Consumption of non-steroidal anti-inflammatory drugs and the development of functional renal impairment in elderly subjects. Results of a case-control study.

AIMS: The aim of the present study was to explore the level of risk associated with community use of non-steroidal anti-inflammatory drugs (NSAIDs). METHODS: We carried out a matched case-control study of the relationship between recent use of NSAIDs and the presence of functional renal impairment present at the time of hospitalisation with a range of clinical problems. Cases (n = 110) were consecutive patients admitted acutely to hospital who had serum creatinine levels greater than or equal to 0.15 mmol l(-1) , which improved by 20% or more within the next 14 days, or prior to discharge from hospital. Controls (n= 189) were subjects of the same sex and age (to within 5 years) as the cases, who were admitted to the same hospital, who had normal serum creatinine levels (<0.12 mmol l(-1) throughout their hospital stay. Information on a number of study factors, including recent use of aspirin and other NSAIDs, was obtained by structured interview. RESULTS: Overall, there was a weak association between consumption of NSAIDs (including non-prophylactic aspirin) and the development of functional renal impairment-adjusted odds ratios (OR) with use of NSAIDs in the previous week or in the previous month: OR 1.5 (95% CI 0.80, 2.9) and 1.8 (95% CI 0.97, 3.4) respectively. In subjects with a previous history of renal disease the adjusted OR was 6.6 (0.75, 57.8) and in those with a history of gout or hyperuricaemia the OR was 7.2 (1.3, 40.2). There was a weak positive relationship between the dose of drug consumed in the previous week and the odds of functional renal impairment. The relationship between risk and published figures for drug half-lives (t1/2) was stronger. The odds ratio increased from 1.2 (95% CI 0.61, 2.4) with a t1/2 < or = 4 h, to 4.8 (1.5, 15.8) with a t1/2 of < or = 12 h (P=0.012, test for trend). This relationship remained statistically significant after adjustment for a number of clinical variables and the dose of drug ingested. CONCLUSIONS: NSAIDs are an important cause of functional renal impairment in subjects with renal disease or a history of gout or hyperuricemia. The half-life of the drug is more important than the ingested dose in determining the risk of this outcome. Long half-life drugs should be avoided in individuals who are at risk of developing renal impairment.

Aged↗
PubMed1997

Atrial natriuretic peptides predict mortality in the elderly.

OBJECTIVES: To ascertain whether atrial natriuretic peptides could be used as prospective and independent predictors of total mortality in an elderly population. DESIGN: Atrial natriuretic peptides, ANP(1-98) and ANP(99-126), were measured in 541 subjects from the 85-year-old population of Gothenburg, Sweden. Before the study cardiovascular disorders such as congestive heart failure, ischaemic heart disease, hypertension and atrial fibrillation were defined. Total mortality was recorded during the prospective 60-month follow-up period. SETTING: Individuals aged 85 years from the population of Gothenburg, Sweden, were visited once at home and made one visit to Vasa Hospital. MAIN OUTCOME MEASURES: Sixty-month mortality in relation to circulating concentrations of atrial natriuretic peptides. RESULTS: Circulating concentrations of ANP(1-98) and ANP(99-126) were significantly correlated with 60-month mortality in the total study population (ANP(1-98), P < 0.001: ANP(99-126), P < 0.01). In subjects with cardiovascular disorders, 60-month mortality was significantly correlated with increased concentrations of ANP(1-98) (P < 0.01) and ANP(99-126) (P < 0.05). In subjects with no defined cardiovascular disorder, 60-month mortality was significantly correlated with increased ANP(1-98) concentrations (P < 0.01). CONCLUSIONS: In the elderly population, atrial peptides predict mortality in subjects with defined cardiovascular disorders as well as in the total population and may predict future cardiovascular disorder.

Aged↗
PubMed1997

Recalling demonstrated and guided movements using imaginary and verbal rehearsal strategies.

This study investigated the recall of movement patterns presented either by demonstration or guided movement with vision eliminated. Participants were instructed to rehearse and remember each of the 12 patterns using one of four strategies: imagery, verbal labeling, imagery and verbal labeling, or no rehearsal strategy (i.e., control condition). Recall was better for patterns that were demonstrated than for those presented via guided movement. In addition, more patterns were remembered if a combination of imagery and verbal labeling were employed as a rehearsal strategy compared to using imagery alone. These results are discussed using Annett's (1994) model showing the relationships between action, language, and imagination in the acquisition of motor skills.

Analysis of Variance↗
PubMed1997

Gas exchange and neurohumoral response to exercise: influence of the exercise protocol.

Maximal oxygen uptake varies with the exercise protocol, but the extent to which hormonal and metabolic responses to exercise are influenced by the exercise protocol has not been precisely defined. Twelve healthy subjects underwent maximal exercise testing using two incremental bicycle tests with individualized, identical work rate increments between 40 and 70 W. One protocol employed a 1-min and the other a 3-min duration per stage. Expiratory gas and venous blood were sampled at regular intervals for metabolic and hormonal analysis. Exercise duration for the 1-min and 3-min protocols was 6.0 +/- 0.1 and 14.3 +/- 0.3 min, respectively (P < 0.001). Significantly higher values were observed for peak VO2 and maximal ventilation during the 3-min protocol compared with the 1-min protocol (41.1 +/- 1.8 vs 38.3 +/- 1.6 ml.kg-1.min-1, P < 0.001; and 104.9 +/- 8.0 vs 97.2 + 5.7 l.min-1, P < 0.05, for peak VO2 and peak ventilation, respectively). However, the maximal workload achieved was higher during the 1-min versus the 3-min protocol (330 + 24 vs 280 + 21 W, P < 0.01). No differences were observed for maximal heart rate or blood pressure, whereas maximal plasma lactate was roughly twice as high during the 3-min compared with the 1-min protocol (7.5 +/- 0.8 vs 3.8 +/- 0.5 mmol.l-1, P < 0.001). Norepinephrine, epinephrine, dopamine, and growth hormone levels were generally higher throughout exercise during the 3-min compared with the 1-min protocol. When expressed as a percentage of peak VO2, however, differences in catecholamine levels were not observed. Endothelin levels did not change. We conclude that the exercise protocol profoundly influences exercise capacity as well as the metabolic and hormonal response to exercise and should be considered when using these variables to evaluate an intervention.

Adult↗
PubMed1997

Effect of bolus injection versus continuous infusion of furosemide on diuresis and neurohormonal activation in patients with severe congestive heart failure.

Previous studies have demonstrated that continuous infusion of furosemide results in increased diuresis and natriuresis compared with bolus administration of the drug in patients with severe heart failure. We reasoned that continuous infusion of furosemide caused less activation of neurohumoral mechanisms, since other studies have shown that bolus administration of furosemide may activate this system. We therefore tested the hypothesis that continuous administration of furosemide would increase water and sodium excretion due to less activation of neurohormones. Eight patients with severe heart failure were studied during continuous infusion over 24 h and bolus injections of furosemide twice daily in a randomized cross-over study. Bolus administration of furosemide increased diuresis and natriuresis significantly in the first 4 h after administration compared with continuous administration, but this was later reversed, resulting in similar 24 h total output. The neurohormones measured at baseline were all markedly elevated. Neither regimens of furosemide caused any further significant changes in neurohumoral response except that pro-ANF decreased more during the first 8 h after bolus administration compared to continuous infusion. This study has demonstrated that bolus administration of furosemide in conventional doses is equally effective as continuous intravenous infusion in patients with severe heart failure. This may be due to maximal neurohormonal activation in severe heart failure (NYHA III-IV) which could not be further activated by bolus administration.

Atrial Natriuretic Factor↗
PubMed1997

Stable neurological function in subjects treated with 2'3'-dideoxyinosine.

AIDS Dementia Complex (ADC) is a frequent and devastating complication of HIV infection. There is evidence that zidovudine (ZDV) has an effect in alleviating the symptoms of ADC, and may have a role in its prevention. It is therefore important that new antiretroviral therapies be evaluated not only for the risk of neurologic side effects, but also for their relative efficacy to ZDV in the prevention of ADC. The present study reports the effects of 2'3'-dideoxyinosine (DDI, didanosine, Videx) therapy on neuropsychological performance in the context of several large clinical trials targeting advanced systemic HIV-1 infection. Subjects treated with DDI had stable neurologic performance in quantitative tests over a 1 year period and were similar to zidovudine treated subjects.

AIDS Dementia Complex↗
PubMed1997

Estimation of transplacental and nonplacental diphenhydramine clearances in the fetal lamb: the impact of fetal first-pass hepatic drug uptake.

Previous estimates of maternal and fetal placental and nonplacental clearances in pregnant sheep using a two-compartment open model have revealed higher values of fetal placental clearance (CLfm) compared to the maternal placental clearance (CLmf) for most drugs. This includes the antihistamine diphenhydramine (DPHM), which also has the highest weight-corrected fetal nonplacental clearance (CLfo) among the drugs studied. This study was designed to determine the reasons for this CLfm - CLmf difference and to identify the sites of high CLfo for DPHM. DPHM and a stable isotope-labeled analog, [2H(10)]DPHM, were simultaneously infused to steady state to the mother and fetus, respectively, in five pregnant sheep. CLmf, CLfm, CLmo and CLfo averaged 50.3 +/- 13.2, 214.4 +/- 30.8, 36.6 +/- 1.9 and 109.8 +/- 22.3 ml/min(-1)/kg(-1), respectively. By measuring diphenylmethoxyacetic acid and [2H(10)]diphenylmethoxyacetic acid levels in samples obtained from our previous study of fetal hepatic first-pass DPHM uptake, the hepatic first-pass extraction ratio of the drug from umbilical venous blood was estimated to be 0.44 +/- 0.05. This can account for virtually all of CLfo. Fetal hepatic first-pass uptake of maternally derived DPHM in the paired infusion study reduces the fetal/maternal plasma DPHM concentration ratio and results in significant underestimation of CLmf. When the CLmf estimate is corrected for this factor and for maternal-fetal DPHM plasma protein binding differences, its value approaches CLfm. Fetal hepatic first-pass uptake may also be a factor in the underestimation of CLmf for most of the other drugs. Conversely, a lower value of CLmf compared with CLfm provides evidence for significant fetal hepatic uptake of these compounds.

Animals↗
PubMed1996

Regulation of phosphorylation pathways by p21 GTPases. The p21 Ras-related Rho subfamily and its role in phosphorylation signalling pathways.

The oncogenic Ras p21 GTPases regulate phosphorylation pathways that underlie a wealth of activities, including growth and differentiation, in organisms ranging from yeast to human. In metazoa, growth factors trigger conversion of Ras from an inactive GDP-bound form to an active GTP-bound form. This activation of Ras leads to activation of Raf. Raf is one of the initial kinases in the cytoplasmic mitogen-activated protein kinase (MAPK) cascade, involving extracellular-signal-regulated kinases (ERK), which culminates in nuclear transcription. The Ras-related subfamily of Rho p21s, including Rho, Rac and Cdc42 are similarly active in their GTP-bound forms. These p21s mediate growth-factor-induced morphological changes involving actin-based cellular structures. For example, in mammalian fibroblasts, Rho mediates the formation of cytoskeletal stress fibres induced by lysophosphatidic acid, while Rac mediates the formation of membrane ruffles induced by platelet-derived growth factor, and Cdc42 mediates the formation of peripheral filopodia by bradykinin. In some cases, factor-induced Rac activation results in Rho activation, and factor-induced Cdc42 activation leads to Rac activation, as determined by specific morphological changes. Although separate Cdc42/Rac and Rac/Rho hierarchies exist, these might not extend into a linear form (i.e. Cdc42-->Rac-->Rho) since Cdc42 and Rho activities may be competitive or even antagonistic. Thus Cdc42-mediated formation of filopodia is accompanied by loss of stress fibres (whose formation is mediated by Rho). Recently, mammalian kinases that bind to the GTP-bound forms of Rho p21s have been isolated. These kinases include the p21-activated serine/threonine kinase (PAK), which is stimulated by binding to Cdc42 and Rac, and the Rho-binding serine/threonine kinase (ROK), which is not as strongly stimulated by binding. These kinases act as effectors for their p21 partners since they can directly affect the reorganization of the relevant actin-containing structures. ROK promotes the formation of Rho-induced actin-containing stress fibres and focal-adhesion complexes, to which the ends of the stress fibres attach. PAK stimulates the disassembly of stress fibres, which has been shown to accompany formation of Cdc42-induced peripheral-actin-containing structures, including filopodia, which with Rac-induced membrane ruffles play a role in cell movement. PAK also fosters loss of focal-adhesion complexes. Thus, there is cooperation between different Rho p21s as well as antagonism, with their associated kinases having a role in the integration of the reorganization of the actin cytoskeleton. The similarity of PAK to the Saccharomyces cerevisiae kinase Ste20p, which initiates the yeast mating/pheromone MAPK cascade, led to experiments showing that Cdc42 regulates Ste20p in this MAPK pathway. This similarity has also led to the demonstration that mammalian Cdc42 and Rac can signal to the nucleus through MAPK pathways. However, c-Jun N-terminal kinase (JNK, stress-activated protein kinase) rather than ERK, is involved. PAK have been implicated in the JNK pathway, but their exact roles are uncertain. Thus members of the Rho subfamily, and kinases that bind to these p21s are intimately involved in immediate morphological processes as well as long-term transcriptional events.

Animals↗
PubMed1996

Structure-activity relationship of 17 structural analogues of n-butyric acid upon c-myc expression.

Terminal differentiation of hematopoietic cells in vivo and in vitro is almost invariably accompanied by down-regulated expression of the c-myc proto-oncogene. Constitutive expression of c-myc in tumor cells inhibits terminal differentiation and maintains proliferation. In Burkitt's lymphoma, chromosomal translocations cause a deregulation of the c-myc gene through fusion of this locus with one of the immunoglobulin gene loci. However, the down-regulation of c-myc by n-butyric acid, a potent inducer of differentiation, is also observed in BL cells. Unlike other inducers of differentiation such as dimethylsulfoxide or hexamethylenebisacetamide, which down-regulate c-myc expression, albeit transiently, n-butyric acid causes a continuous, transcriptional shut-off. Because of the possible therapeutic implication of this finding, we have assayed structural analogues of n-butyric acid for their effect on c-myc expression in Burkitt's lymphoma cells. Of the analogues tested, 12 were active and 5 were inactive. Only unbranched fatty acids with 4 and 5 carbon atoms showed activity, a 4-carbon chain being optimal. 3-chloropropionic acid had maximal activity at a 3-fold lower concentration than n-butyric acid (1 mM versus 3 mM). The corresponding ester-analogues were equally effective. Those analogues found capable of down-regulating c-myc in Burkitt's lymphoma cells were similarly effective in their ability to induce terminal differentiation in murine erythroleukemia cells.

Animals↗
PubMed1996

Characterisation of the possible effect on birthweight following frequent prenatal ultrasound examinations.

The objective of this study was to evaluate and characterise by study of newborn biometry a possible effect on birthweight which we observed previously in a randomised controlled trial of multiple prenatal ultrasound examinations. A total of 2743 women with single pregnancies had been allocated at random to either a protocol of ultrasound imaging and continuous wave Doppler studies at 18, 24, 28, 34 and 38 weeks gestation (intensive group), or to a protocol of a single imaging examination at 18 weeks and further imaging scans only as clinically indicated (regular group). When compared with those in the regular group, and adjusted for other confounding variables, normally formed babies of term gestational age in the intensive group tended to be shorter when measured at birth (P = 0.123) and on day 2-3 of age (P = 0.068). There were statistically insignificant reductions in the circumferences of the chest, abdomen and mid-arm; and in the skinfold thicknesses of the triceps, parascapular and subscapular regions. Principal component analysis showed a trend for a reduction for the skeletal component (P = 0.085) but not for the soft tissue component (P = 0.332). Comparison of the neonatal biometry in the two groups is not conclusive, but the differential effects on the various growth parameters suggest that if multiple scans do indeed restrict fetal growth, the mechanism is more likely to be an effect on bone growth rather than a reduction in nutrient supply from the placenta.

Biometry↗
PubMed1996

[Pro-atrial natriuretic factor is predictive for the clinical status of patients with heart failure].

This study was undertaken in order to evaluate the relationship between N-terminal proatrial natriuretic factor [1-98] and routinely available measures of clinical status. Odds ratio estimates demonstrated a much higher risk of presence of left ventricular dysfunction and dilatation, pulmonary hypertension, and New York Heart Association function class III or IV with increasing proANF values. Analysis is simple and can be of practical value as a supplement in the assessment of cardiac status in this heterogeneous population.

Adolescent↗
PubMed1996

Treatment of non-disseminated cancer of the lower rectum.

Apart from the occasional tumour which is suitable for local excision, most low rectal cancers are best treated by anterior resection with complete removal of the rectum; the construction of a coloanal reservoir should allow routine sphincter saving. This surgery may be carried out independently of adjuvant radiotherapy which, if given, should be administered before operation.

Humans↗