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Biomedical subjects

C Clarke

Publications and source records attributed to C Clarke.

At least 73 records · Page 4Linked to original sources
PubMed1996

Night cough in a population-based sample of children: characteristics, relation to symptoms and associations with measures of asthma severity.

Nocturnal cough in asthma is a common but poorly understood phenomenon. The aims of this study were to determine the relationship between recorded night cough, reported night cough and current wheeze in a population-based sample of children previously identified as wheezy, and to examine the relationship of nocturnal cough to current symptoms, markers of asthma severity and environmental exposure. Children were reassessed in the early school years by measuring current symptoms, ventilatory function, bronchial reactivity, peak flow variability, respiratory symptom diaries and home monitoring of overnight cough, transcutaneous arterial oxygen saturation, room temperature and humidity. Night studies were performed on 59 asymptomatic children and 41 children with current wheeze. Cough occurred more frequently in current wheezers compared to asymptomatic children (16 out of 41 (39%) vs 11 out of 59 (19%)), and more cough episodes were recorded (median 3.5 vs 2.0). Night cough was not associated with bronchial reactivity, peak flow variability, degree of morning dip, mean overnight arterial oxygen saturation, ventilatory function, maternal smoking or treatment of asthma. However, it was associated with lower overnight air temperature. Although night cough is more common in current wheezers, there is poor agreement between recorded and reported night cough. Objective tests of asthma severity are of little use in predicting its presence in this age group. The sleeping environment deserves further study.

Asthma↗
PubMed1996

Ethanolamine and choline phospholipids in nascent very-low-density lipoprotein particles.

OBJECTIVE: To establish methods to examine the polar lipids of triglyceride-rich lipoproteins (TRLs) and to examine postprandial changes in glycerophosphocholine (PC) and glycerophosphoethanolamine (PE) polar lipids and in the ratio of diacyl to alkenylacyl components. The membrane phospholipids of TRLs have received little attention. PC and PE constitute major fractions and both comprise diacyl- and alkenylacyl-phospholipids. There has been recent interest in possible antioxidant properties of alkenylacyl (plasmalogen) PE. DESIGN: Analysis of PE and PC fractions in blood samples taken from the subjects while fasting and at four 2-h intervals after eating a 4749-kJ breakfast. PARTICIPANTS: Five healthy subjects. OUTCOME MEASURES: Levels of PE and PC fractions isolated from blood samples by ultracentrifugation (to isolate the d < 1.006 fraction of plasma) and reversed-phase chromatography. RESULTS: The concentration of triglyceride in particles of density less than 1.006 g/cm2 in the samples increased rapidly, peaking 4 h after the meal at 0.51 mmol/L above the fasting level. Apolipoprotein B-48 was maximal in the sample taken 2 h after eating and below 1%, as a percentage of apolipoproteins B-48 and B-100, in all other samples. The concentration of PC exceeded that of PE by an order of magnitude, but there was a proportionately greater increase in PE postprandially. PE contained a rapidly cleared alkenylacyl fraction, which was maximal (at a threefold increase over the baseline level) in the sample taken 4 h after eating. CONCLUSIONS: As blood triglyceride levels rise and fall postprandially, the polar lipid composition of the TRLs also changes; these changes are more marked in the PE than in the PC fraction. The fact that the level of the PE fraction peaked later (at 4 h after eating) than that of B-48 apolipoprotein (which peaked at 2 h after eating) suggests that the peak in the PE fraction had a hepatic (very-low-density lipoprotein) origin. Alkenylacyl (plasmalogen) phospholipid accompanied both PE and PC fractions but was about 10 times greater in PE. This result is significant if alkenylacyl PE does indeed function as an antioxidant.

Chromatography, High Pressure Liquid↗
PubMed1995

Kabuki syndrome-like features in monozygotic twin boys with a pseudodicentric chromosome 13.

We present monozygotic twin boys with features of Kabuki syndrome. The twins were discordant for cleft palate and coarctation of the aorta. The occurrence of Kabuki syndrome in monozygotic twins has not been previously reported and reinforces the belief that this condition has a genetic basis. Chromosomal analysis on the boys showed a pseudodicentric chromosome 13 with an inactive centromere and satellite stalks at 13q12.11: 46,XY,psu dic(13)(13pter-->13q12.11::13p12-->13q11.00:: 13q12.11-->13qter). Their phenotypically normal mother appears to carry the same pseudodicentric chromosome 13.

Abnormalities, Multiple↗
PubMed1995

The natural history of respiratory symptoms in preschool children.

We studied the natural history of preschool respiratory symptoms in a population-based sample of children followed during the early school years. Current symptoms, ventilatory function, bronchial responsiveness to methacholine (BR), atopic status, and peak expiratory flow variability (PEFV) were assessed. Among those initially asymptomatic (210 subjects), 83.3% remained symptom-free, 6.7% started to wheeze, and 10% developed recurrent cough. Nearly half (46.9%) of the initial wheezing group (145 subjects) became symptom-free, 37.9% continued to wheeze, and 15.2% reported recurrent cough. Over half (56.0%) of the cough group (127 subjects) became symptom-free, 7.2% developed wheeze, and 36.8% reported continuing cough. Preschool wheezers showed the greatest BR (geometric mean 1.91 mg/ml) and the highest atopic prevalence (AP) (43.6%) when compared with the preschool asymptomatic group (BR: 3.39 mg/ml; AP: 23.8%) and the cough group (BR: 2.62 mg/ml; AP: 26.7%) (p = 0.0001 and p = 0.006 respectively). Children whose wheeze had persisted from the preschool period exhibited the poorest ventilatory function, the highest BR, a high AP, and high PEFV. The study shows that fewer than half of preschool wheezy children continued to wheeze in the early school years but those with persistent wheeze display many of the clinical characteristics consistent with a diagnosis of asthma.

Age Factors↗
PubMed1994

Ultrastructural localization of BHRF1: an Epstein-Barr virus gene product which has homology with bcl-2.

BHRF1 is an Epstein-Barr virus encoded protein which has a 38% sequence similarity with bcl-2 over the carboxyl portion. Like bcl-2, BHRF1 has been shown to suppress programmed cell death from apoptosis. Previously BHRF1 has been detected in mitochondrial, microsomal, and nuclear compartments by cell fractionation analysis. In this study we have used the technique of immunoelectron microscopy to define the ultrastructural distribution of the BHRF1 product in the EBV converted cell lines B95.8 and P3HR-1. The BHRF1 product was localized at the periphery of the mitochondria in a pattern similar to that of bcl-2 and by analogy with bcl-2 this is likely to be the functional destination. Sequence analysis of the BHRF1 protein disclosed similarity with the recently described bcl-2 homologues bcl-x (32%) and bax (34%) over the carboxyl portion, with several domains of complete identity. BHRF1 appears to be a member of a gene family involved in the regulation of programmed cell death. The identity between BHRF1 and bcl-2, an apparent shared ability to abrogate apoptosis, and the common ultrastructural localization is compelling and suggests that bcl-2 and BHRF1 are both functionally and mechanistically similar.

Amino Acid Sequence↗
PubMed1994

Effects of gestational exposure to monoamine oxidase inhibitors in rats: preliminary behavioral and neurochemical studies.

Monoamine neurotransmitters are important in the development of the immature mammalian brain, prior to assuming their role as neurotransmitters. The endogenous levels of these transmitters are highly regulated by the enzyme monoamine oxidase (MAO). Thus, any change in this enzyme should have a profound effect on brain development. In order to test this hypothesis, we treated developing rat pups with the monoamine oxidase inhibitors (MAO-Is), clorgyline (MAO-A, 3 mg/kg), and deprenyl (MAO-B, 3 mg/kg) throughout gestation (MAO-I-birth), or throughout gestation and to sacrifice (MAO-I-sac). The animals were analyzed for serotonin and dopamine terminal density, using 3H-paroxetine and 3H-GBR 12935, respectively. Whereas there were no changes in the development of the dopamine system, the serotonin system was severely affected, particularly in the cortex that showed a significant reduction of innervation at 30 days postnatal. The animals reached all normal development milestones on schedule, and had no changes in measures of anxiety (% light/dark); however, the animals showed increased open field activity and deficits in a passive avoidance paradigm, which may be a measure of impulsivity. The MAO-I-sac animals were severely impaired, showing stereotypic behavior, seizures, and eventually visual impairments. Our results are discussed in terms of relevance to human disease states, such as atypical Norrie's disease, impulsivity, and hyperactivity. As well, our results should be used to caution against the use of MAO-Is in women of child-bearing age.

Animals↗
PubMed1994

Comparison of oral erythromycin formulations in the horse using pharmacokinetic profiles.

The pharmacokinetic properties of four erythromycin formulations were compared in six adult horses after administration of single and multiple oral doses. Formulations of erythromycin administered were estolate and phosphate given 37.5 mg/kg every 12 h and 25 mg/kg every 8 h, and stearate and ethylsuccinate given 25 mg/kg every 8 h. Areas under the curve (AUC) and maximum plasma erythromycin concentrations (Cmax) were equal or greater (P > or = 0.05) following administration of erythromycin phosphate and stearate compared with those values following administration of erythromycin estolate or ethylsuccinate. In comparing an 8 h vs. a 12 h dosage interval for multiple doses of erythromycin phosphate or estolate, there were no significant differences observed in AUC(24-28 h), peak-trough plasma concentrations or duration that plasma concentrations exceeded the minimal inhibitory concentration (MIC) for Rhodococcus equi. Comparisons of pharmacokinetic parameters between single and multiple doses were made for each formulation. Differences in Cmax, tmax, or t1/2 beta between single and multiple doses were demonstrated for erythromycin ethylsuccinate and estolate. Based on equivalent plasma antibiotic concentrations, erythromycin phosphate or stearate could be substituted for estolate in the treatment of Rhodococcus equi pneumonia. Furthermore, there was no advantage of an 8-h interval, compared with an interval of 12 h.

Actinomycetales Infections↗
PubMed1994

Day-night blood pressure variation in normotensive, normoalbuminuric type I diabetic subjects. Dippers and non-dippers.

OBJECTIVE: To examine day-night blood pressure (BP) variation in normotensive, normoalbuminuric subjects with type I diabetes and to assess the prevalence of an impaired nocturnal BP fall. RESEARCH DESIGN AND METHODS: Fourteen healthy volunteers and 13 normotensive, normoalbuminuric subjects with type I diabetes were studied with an ambulatory sphygmomanometric device for 24 h. RESULTS: No significant difference was found between diabetic and control groups with regard to daytime systolic blood pressure (sBP) or diastolic blood pressure (dBP). However, the mean nighttime sBPs (P < 0.01) and dBPs (P = 0.01) were significantly higher in the diabetic group compared with the control group. Furthermore, the night/day ratio for both sBP (P < 0.01) and dBP (P < 0.01) was significantly higher in the diabetic group. Approximately half of the diabetic subjects studied were non-dippers when defined either by a nocturnal fall in sBP/dBP of < 10/5 mmHg (5/13 vs. 0/14, P < 0.05: diabetic group vs. control group) or a day to night fall in either sBP (7/13 vs. 2/14, P < 0.05) or dBP (6/13 vs. 0/14, P < 0.01) of < 10%. CONCLUSIONS: Ambulatory BP may reveal impaired nocturnal BP fall in normotensive, normoalbuminuric subjects with type I diabetes. These subjects may be at greater risk of certain complications as a consequence of an increased BP burden.

Adult↗
PubMed1994

An immunomagnetic separation method using superparamagnetic (MACS) beads for large-scale purification of human mammary luminal and myoepithelial cells.

A comparison has been made between different immunomagnetic techniques for separating normal human mammary epithelial cells based on the exclusive expression of EMA (epithelial membrane antigen) by luminal cells and CALLA (CD10) by myoepithelial cells. When cells labelled with antibodies to these antigens were incubated with Dynabeads, they rosetted myoepithelial but not luminal cells. However, both luminal and myoepithelial cells could be positively separated using the MACS system. Purity was established by analyzing the expression of CALLA and EMA using flow cytometry, and of cell-type specific cytokeratins using indirect immunofluorescence. Dynabead-separated myoepithelial cell populations were of high purity (> 98%) but the beads could not be removed from the cells. Luminal cell populations separated by the MACS method were also highly purified (> 95%), as were myoepithelial cell populations (> 90%). Using this immunomagnetic separation method, up to 10(7) cells of each type could be obtained from individual preparations.

Adolescent↗
PubMed1993

Localization of 5-HT1A receptors to astroglial cells in adult rats: implications for neuronal-glial interactions and psychoactive drug mechanism of action.

Although tissue culture studies have shown a variety of neurotransmitter receptors on astroglial cells, verifying these observations in adult animals has been difficult and rarely accomplished. In the current study we have used double immunocytochemistry to localize 5-HT1a receptors to astroglial cells in fixed sections of adult rat brain. The astroglial cells were identified using an antibody raised against the astroglial-specific protein glial fibrillary acidic protein (GFAP). To label the 5-HT1a receptor, we used an antibody we recently raised against a unique peptide sequence occurring in the second extracellular loop of the receptor. Our results show that the 5-HT1a receptor occurs in relatively high abundance on astroglial cells. There is regional specificity, the receptor being much more commonly found in septum and hippocampus than striatum. There are also intraregional differences in that even within a single brain region one astrocyte may have very high levels of the receptor while an adjacent cell has none. We propose that the cellular localization of this receptor could have significance in understanding the mechanism of action of 5-HT1a receptor active drugs in alleviating anxiety and depression. The mechanism may be through the release of a neurotrophic agent, S-100 beta, from astrocytes. This factor may then cause regeneration or sprouting of neuronal terminals which have been lost due to a disease process.

Animals↗
PubMed1993

Chemical identification of the mammalian oxytocin in a holocephalian fish, the ratfish (Hydrolagus colliei).

The neurohypophysial hormones of the ratfish (Hydrolagus colliei), a species belonging to the subclass Holocephali of cartilaginous fishes, have been investigated. An oxytocin-like hormone has been isolated from acetone-desiccated pituitary glands by using successively molecular sieving and high-pressure liquid chromatography. The peptide has been identified as oxytocin by coelution with synthetic oxytocin in HPLC, amino acid sequencing, mass spectrometry, and C-terminal sequencing through carboxypeptidase Y. Vasotocin may be present in a very small amount. Cartilaginous fishes appear to display a great diversity in their oxytocin-like hormones since five different peptides have been identified in rays and sharks that belong to the second subclass Selachii.

Amino Acid Sequence↗
PubMed1993

Anesthesia for thoracoscopic laser ablation of bullous emphysema.

BACKGROUND: We describe the anesthetic management for a new surgical procedure: laser ablation of emphysematous bullae via thoracoscope. Although thoracoscopy is not new, this is the first description of a series of patients with bilateral, chronic lung disease who underwent long periods of one-lung ventilation (OLV) during thoracoscopic therapy. METHODS: Twenty-six laser ablation procedures were performed in 22 patients. The patients were elderly (mean age 63 yr) with a large incidence of coexisting cardiovascular disease. Most required chronic home oxygen therapy. Patients were monitored invasively, and hemodynamic data were recorded every 5 min. Arterial blood gas analyses were performed every 15 min. Comparisons were made between three intraoperative periods: two-lung ventilation (TLV) before thoracoscopy, OLV during thoracoscopy, and TLV after thoracoscopy. RESULTS: All patients survived the operation despite a mean OLV duration of 170 min, but several experienced serious intraoperative problems, such as hypoxemia or hypotension. Hypoxemia was treated with nondependent lung continuous positive airway pressure and dependent lung positive end-expiratory pressure. In all patients the lungs were adequately ventilated, but bronchopleural fistulae occurred upon return to TLV in every case. The resulting air leaks, often 50% of inspired tidal volume, required the use of a pressure-cycled ventilator to maintain oxygenation. Postoperative air leaks greater than 50% of inspired tidal volume usually required subsequent surgical correction, while smaller leaks resolved spontaneously. Mechanical ventilation was required for an average of 5 days. Eighty-four percent have survived at least 6 months, and nearly all survivors report symptomatic improvement. CONCLUSIONS: Ablation of bullae appears to provide symptomatic improvement, and thoracoscopy might be better tolerated than thoracotomy, especially in patients with severe bullous emphysema.

Aged↗
PubMed1993

Dupuytren's contracture in pensioners at the Royal Hospital Chelsea.

Dupuytren's disease of the hands was present in 55 (13.75%) of the 400 elderly ex-servicemen living at the Royal Hospital Chelsea. Five men (9.1%) reported the condition in either a parent or sibling, but none was aware of an affected child. The prevalence of heavy drinking, non-insulin dependent diabetes or manual occupation was statistically the same in those with or without the condition. Overall, both hands were equally affected, but they differed in severity in 29 men. In milder cases the left hand was the more severely affected (grades 1 and 2); the reverse was true when the difference in severity was greater (grade 3). Since the original description of Dupuytren's disease [1] attempts have been made to link it with a variety of other conditions. These have included trauma, alcoholism and cirrhosis, [2] epilepsy [3] and diabetes mellitus [4]. A genetic link is accepted [5]. The condition is more common in men than women and becomes increasingly common with advancing age [6]. The prevalence in elderly men has been reported as high as 28.9%, rising to 64.3% in surveys of affected families [7]. There are still many physicians who, with a knowing wink when they spot that one of their patients has a Dupuytren's contracture, mentally register that he is an alcoholic. This paper is an attempt to disprove this fairy story. It describes a survey of Dupuytren's disease in a population of elderly men drawn from all parts of the United Kingdom and Ireland.

Aged↗
PubMed1992

Comparative efficacy and safety of amorolfine nail lacquer 5% in onychomycosis, once-weekly versus twice-weekly.

Amorolfine is a new topical antifungal of the phenylpropyl morpholine class which is highly active both in vitro and in vivo against yeasts, dermatophytes and moulds responsible for superficial fungal infections. Human pharmacological studies have established that amorolfine has a persistent antifungal effect in the nail bed and in the skin without being systemically absorbed. This has been confirmed by clinical work showing that amorolfine is effective in treating dermatomycoses and onychomycoses when administered as cream or nail lacquer. It is ineffective when given orally for systemic mycoses or bacterial infections in animals. In earlier studies a 5% concentration of amorolfine nail lacquer was found to produce a better cure rate in onychomycosis than a lower concentration of 2%. From data available on the penetration of amorolfine and on the persistence of mycologically relevant tissue concentrations, it appeared likely that once- or twice-weekly application of nail lacquer should suffice to produce a satisfactory therapeutic effect in onychomycosis. The aim of this investigation was to assess the efficacy and tolerability of 5% amorolfine nail lacquer given once versus twice weekly to patients with onychomycosis of finger nails and toe nails.

Administration, Topical↗