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Biomedical subjects

A Bush

Publications and source records attributed to A Bush.

At least 91 records · Page 5Linked to original sources
PubMed2001

Primary ciliary dyskinesia syndrome associated with abnormal ciliary orientation in infants.

Primary ciliary dyskinesia (PCD) syndrome associated with abnormal ciliary orientation but with normal ciliary ultrastructure has been described in adults, but there are no normal ranges for orientation in infants, despite the fact that half of all patients with PCD present in the new-born period. Nasal brush biopsies were obtained from eight infants (three males), mean age 13.1 months, range 7-23, in order to determine ciliary orientation. They had no upper or lower airway disease and normal organ arrangement and were undergoing general anaesthesia for other reasons. Two infants with typical PCD syndrome but normal ultrastructure of individual cilia also had orientation studies. In the eight normal subjects, a mean of 254 central pairs was examined, range 82-453. The mean ciliary orientation was 14.9 degrees, range 12.9-17.5. The two infants with PCD syndrome but normal ultrastructure of individual cilia had ciliary orientation of (Case 1) 44.5 degrees (range 10.6-64.5) in 218 central pairs; and on a second occasion, 28.9 degrees, (range 9.0-47.5) in 259 central pairs; for Case 2, 24.4 degrees, (range 13.1-38.4) in 196 central pairs. The normal range for ciliary orientation is similar in infants to that described in other work in adults. The two cases of phenotypic primary ciliary dyskinesia in the presence of normal ciliary ultrastructure but abnormal ciliary orientation in infants supports the contention that measurement of ciliary orientation should be part of the assessment of ciliary structure and function in cases of possible primary ciliary dyskinesia, in particular when the ultrastructure of individual cilia appear to be normal.

Cilia↗
PubMed2001

Glycophosphatidylinositol-anchored proteins in Paramecium tetraurelia: possible role in chemoresponse.

We have begun to characterize the glycophosphatidylinositol (GPI)-anchored proteins of the Paramecium tetraurelia cell body surface where receptors and binding sites for attractant stimuli are found. We demonstrate here (i) that inositol-specific exogenous phospholipase C (PLC) treatment of the cell body membranes (pellicles) removes proteins with GPI anchors, (ii) that, as in P. primaurelia, there is an endogenous lipase that responds differently to PLC inhibitors compared with its response to an exogenous PLC, (iii) that salt and ethanol treatment of cells removes GPI-anchored proteins from whole, intact cells, (iv) that Triton X-114 phase partitioning shows that many GPI-anchored proteins are cleaved from pellicles by the endogenous lipase and enter the aqueous phase, and (v) that integral membrane proteins are not among those cleaved with PLC or in the salt/ethanol wash. Antisera against the proteins removed by the salt/ethanol washing procedure include antibodies against large surface antigens, which we confirm in this species to be GPI-anchored, and against an array of proteins of smaller molecular mass. These antisera specifically block the chemoresponse to some stimuli, such as folate, which we suggest are signaled through GPI-anchored receptors. Responses to cyclic AMP, which we believe involve an integral membrane protein receptor, and to NH4Cl, which requires no receptor, are not affected by the antisera. Antiserum against a mammalian GPI-anchored folate-binding protein recognizes a single band among the GPI-anchored salt and ethanol wash proteins. The same antiserum specifically blocks the chemoresponse to folate.

Animals↗
PubMed2001

Cystic fibrosis: review of the decade.

The median estimated life expectancy of children with cystic fibrosis (CF) born in 1990 is 40 years which represents a doubling in the last 20 years, and nearly half of all patients are now adults. Since the identification of the gene, more than 1000 gene mutations have been discovered. This gene encodes for the cystic fibrosis transmembrane conductance regulator (CFTR), a protein that is thought to have a role in ion transport, mucus rheology, inflammation and bacterial adherence. Various therapeutic mechanisms are currently being investigated in an attempt to overcome these abnormalities. Recombinant human DNase is beneficial in many patients and the use of anti-inflammatory agents such as steroids, ibuprofen and macrolides have potential. Despite these advances in treatment it is essential that these patients are diagnosed early. Whilst the case for neonatal screening is not absolutely conclusive the evidence is highly suggestive that it would be beneficial. It may be that, in the future, new treatments such as gene therapy will be more effective in those patients who have not yet developed lung disease. Whilst gene therapy and other new treatments such as bilateral living lobar lung donation give our patients optimism for the future it is important to remember that the increase in survival is a result of good physiotherapy, nutrition, aggressive antibiotic use and an increase in our understanding of the disease. It is important that patients continue to be referred early to tertiary CF centres.

Adolescent↗
PubMed2000

Severe airflow limitation after the unifocalization procedure: clinical and morphological correlates.

BACKGROUND: While unifocalization techniques have improved the treatment options in patients with pulmonary atresia, ventricular septal defect (PA-VSD), and major aortopulmonary collaterals (MAPCAs), severe airflow limitation contributes to significant early postoperative morbidity and mortality. Although this has been attributed to bronchospasm, characteristically it is refractory to bronchodilators, suggesting that other mechanisms may play a role. METHODS AND RESULTS: The clinical course and preoperative angiograms of patients who underwent unifocalization were reviewed. Patients who developed airflow limitation early after surgery underwent fiberoptic bronchoscopy. In addition, the anatomy of the MAPCAs was examined in 14 heart-lung blocks from patients with PA-VSD. Twenty-two procedures were performed in 16 children. Three developed marked airflow limitation early after surgery, necessitating prolonged high-pressure ventilation. Bronchoscopy demonstrated tracheobronchial epithelial necrosis in 2 and signs of tracheobronchial ischemia in the third. Two were successfully extubated after 15 and 16 days, but the third died after 57 days of ventilatory support. Review of the preoperative angiograms demonstrated an extensive peribronchial arterial supply arising from a MAPCA in 1 of the patients who developed severe airway necrosis after unifocalization. This was also obvious in a second patient, but the MAPCA was not included in the unifocalization. In 7 autopsy specimens, MAPCAs contributed to a peribronchial or peritracheal vascular network. Dissection of the distribution of these branches in 2 specimens revealed extensive intrapulmonary peribronchial anastomoses. CONCLUSIONS: Airflow limitation early after unifocalization is related to airway ischemia resulting from interruption of the tracheobronchial blood supply during mobilization of MAPCAs.

Abnormalities, Multiple↗
PubMed2000

Failure of stroke volume augmentation during exercise and dobutamine stress is unrelated to load-independent indexes of right ventricular performance after the Mustard operation.

BACKGROUND: Impaired right ventricular function has been implicated as a cause of reduced maximal exercise capacity after the Mustard operation for transposition of the great arteries. METHODS AND RESULTS: Fourteen asymptomatic survivors of the Mustard operation were studied. Each underwent conventional cardiac catheterization, and after satisfactory hemodynamics were confirmed, load-independent indexes of ventricular function were derived by conductance catheter during dobutamine infusion (0, 5, and 10 microg x kg(-1) x min(-1)). Seven patients also underwent upright exercise testing on a bicycle ergometer with analysis of respiratory gas exchange by continuous mass spectrometry. Accessible pulmonary blood flow was measured at each workload with an automated acetylene rebreathing technique. All patients exercised to a satisfactory end point (respiratory quotient >1.1). Maximum oxygen consumption during exercise was impaired compared with predicted values (mean, 77%; P:<0.02). Both exercise and dobutamine infusion were associated with an increase in cardiac index and heart rate and a reduced stroke volume index response. This was despite significantly improved indexes of myocardial contraction (end-systolic pressure volume relation, P:<0.001), preload recruitable stroke work index (P:<0.01), VA coupling (P:<0.001), and isovolumic relaxation (P:<0.001) during dobutamine infusion. There were no changes observed in end-diastolic pressure-volume relations, but there was failure to augment ventricular filling manifest by absence of change in dV/dt (P:=NS). CONCLUSIONS: The stroke volume response to exercise stress is reduced in patients after the Mustard operation. A similar failure to augment stroke volume occurs during dobutamine stress despite appropriate responses in load-independent indexes of contraction and relaxation. This is due to failure to augment right ventricular filling rates during tachycardia, presumably as a result of impaired AV transport, consequent to the abnormal intra-atrial pathways.

Cardiac Surgical Procedures↗
PubMed2000

Primary ciliary dyskinesia (PCD).

This article summarizes the current state of the scientific and clinical knowledge that relates to primary ciliary dyskinesia (PCD). Although PCD is a rare disease with a prevalence of 1 in 20,000 it has a well recognized morbidity. It is believed that an accurate diagnosis and the application of appropriate management can significantly reduce this morbidity. The cilia themselves are highly complicated organelles that perform important functions, particularly in the respiratory and reproductive tracts, and they have been the focus of many years of research. Our current knowledge of ciliary function and mucociliary clearance is summarized, and the relationship with laterality defects is discussed. A phenotype resembling PCD is also seen in animal models, and some of these are described before reviewing the clinical aspects of PCD in humans and new developments in the field that may have implications for the future investigation and management of affected individuals.

Animals↗
PubMed2000

Targeted chemoradiation for advanced head and neck cancer: analysis of 213 patients.

BACKGROUND: To determine the survival results, patterns of relapse, and organ preservation effects of a targeted chemoradiation protocol for patients with advanced (stage III-IV) carcinoma of the head and neck. METHODS: Analysis of 213 patients with stage III-IV squamous cell carcinoma treated at UT Memphis between June 1993 and March 1998. Treatment included weekly intra-arterial infusions of cisplatin (150 mg/m(2)/ week x 4) rapidly delivered to the tumor bulk, simultaneous intravenous thiosulfate for systemic drug neutralization, and conventional external-beam irradiation (180-200 cGy/fraction) to a total dose of 68-72 Gy. RESULTS: Tumor response, toxicity, disease control above the clavicle, pattern of relapse, and survival. There were 89 events of grade III-IV toxicity and 6 treatment-related deaths (grade V). Complete response in the primary and regional sites was obtained in 171 of 213 (80%) and 92 of 151 (61%), respectively. The rate of clearance of regional disease after neck dissection was 98%. There were 51 of 195 recurrences (26%): 11 local (5.6%), 5 regional (2.6%), and 35 distant (17.9%). The Kaplan Meier plot projections for overall and cancer-related 5-year survival was 38.8% and 53.6%, respectively, whereas disease control above the clavicle was 74.3%. CONCLUSIONS: We believe this chemoradiation protocol represents an effective management scheme for patients with advanced head and neck cancer with a high rate of organ preservation and possibly improved survival.

Adult↗
PubMed2000

Negative pressure ventilation as haemodynamic rescue following surgery for congenital heart disease.

A low cardiac output state is an important cause of morbidity and mortality following repair of tetralogy of Fallot (ToF). This is often refractory to conventional measures. The cardiac output of these patients is highly dependent on diastolic pulmonary arterial flow which is enhanced during spontaneous respiration, but much reduced by intermittent positive pressure ventilation (IPPV). We report the successful use of negative pressure ventilation (NPV) as haemodynamic therapy in three children with a low output secondary to restrictive right ventricular (RV) physiology following ToF repair. NPV produced a significant haemodynamic improvement, with increases in cardiac output of greater than 100 % in two of the children. By augmenting pulmonary blood flow, and hence cardiac output, NPV has a role as adjunctive haemodynamic therapy in patients with a low output secondary to diastolic RV dysfunction, in whom early extubation is not possible.

Cardiac Output, Low↗
PubMed2000

Oxygen consumption after cardiopulmonary bypass surgery in children: determinants and implications.

OBJECTIVE: We sought to assess oxygen consumption and its determinants in children shortly after undergoing cardiopulmonary bypass operations. METHODS: Twenty children, aged 2 months to 15 years (median, 3.75 years), undergoing hypothermic cardiopulmonary bypass operations were studied during the first 4 hours after arrival in the intensive care unit. Central and peripheral temperatures were monitored. Oxygen consumption was continuously measured by using respiratory mass spectrometry. Oxygen delivery was calculated from oxygen consumption and arterial and mixed venous oxygen contents, which were sampled every 30 minutes. Oxygen extraction was derived by the ratio of oxygen consumption and oxygen delivery. Arterial blood lactate levels were measured every 30 minutes. RESULTS: There was a correlation between oxygen consumption and age in patients older than 3 months (r = -0.76). Mean oxygen consumption increased by 14.7% during the study. The increase in oxygen consumption was correlated with the increase in central temperature (r = 0.73). Nine patients had an arterial lactate level above 2 mmol/L on arrival. There were no significant differences in oxygen consumption, oxygen delivery, and oxygen extraction between the group with lactate levels between 2 and 3 mmol/L and the groups with normal lactate levels both on arrival and at 2 hours. One patient with a peak lactate level of 6.8 mmol/L had initially low oxygen delivery (241.3 mL. min(-1). m(-2)). CONCLUSIONS: During the early hours after a pediatric cardiac operation, the increase in oxygen consumption is mainly attributed to the increase in central temperature. Oxygen consumption is negatively related to age. Mild lactatemia is common and does not appear to reflect oxygen delivery or oxygen consumption or a more complicated recovery.

Adolescent↗
PubMed2000

Outcome of paediatric domiciliary mask ventilation in neuromuscular and skeletal disease.

Noninvasive positive pressure ventilation delivered by nasal mask or facemask has been used widely in the last decade to manage chronic ventilatory failure in adults with neuromuscular and chest wall disease. However, it has been thought that paediatric patients would not be able to tolerate masks, and previous anecdotal reports on the paediatric application of mask ventilation have not assessed the effects on nocturnal and arterial blood gas control. Domiciliary mask ventilation has been used in 40 children with ventilatory insufficiency due to congenital neuromuscular and skeletal disease aged 9 months-16 yrs. Eighteen patients had symptomatic nocturnal hypoventilation, 17 had diurnal ventilatory failure, three were referred for weaning and two had frequent chest infections associated with sleep-disordered breathing. Thirty eight of the 40 patients tolerated mask ventilatory support long-term. Diurnal mean+/-SD oxygen tension in arterial blood (Pa,O2) increased from 8.5+/-1.8-10.9+/-1.7 kPa (p<0.001) and mean carbon dioxide tension in arterial blood (Pa,CO2) fell from 7.0+/-1.6-5.9+/-0.8 kPa (p=0.01) following initiation of ventilatory support. Mean and minimum nocturnal Pa,O2 and peak transcutaneous carbon dioxide tension (Ptc,CO2) (n=21) improved significantly. Mask ventilation can be used successfully in young children and reverses ventilatory insufficiency due to congenital neuromuscular and skeletal disease.

Adolescent↗
PubMed2000

Ventilatory variables in normal children during rest and exercise.

The aim of this study was to provide a complete description of normal ventilation at rest and exercise in children and to determine how best to correct for body size. One-hundred and six children aged 8-17 years (55 male) underwent incremental bicycle exercise testing from rest to exhaustion in 3 min, 15 W.m(-2) steps and thence through 9 min recovery. All variables were calculated using helium dilution mixed expired gas analysis together with measures of alveolar gas concentrations from continuous measurement at the mouth, all via an AMIS 2000 quadrupole mass spectrometer. Surface area was the best single measure to correct for body size but always explained <37% of the variance. Thus for example, surface area corrected oxygen consumption at rest in males was greater than females. Data is presented at rest, each work load and at "maximum" exercise. When presented per watt of work at each work load, this permits comparison of adaptability to exercise between sexes and age groups. Exercise appears to terminate when respiration reaches 45 and 40 breaths-min(-1) in males and females respectively and when alveolar oxygen concentrations rise. This simple protocol and near complete data set ought to permit accurate comparison with disease groups.

Adolescent↗
PubMed2000

Cationic lipid-mediated gene transfer to the growing murine and human airway.

Gene therapy in patients with cystic fibrosis may need to be commenced before the onset of lung disease which may be evident as early as 4 weeks after birth. We assessed the efficacy of cationic lipid-mediated transfer of a reporter gene, chloramphenicol acetyltransferase, in the growing murine and human respiratory tract. Gene expression was greater in adult mice (greater than 8 weeks old) compared with 9- and 16-day-old animals, despite a relatively greater proportion of complex delivered to the younger mice. Subsequent experiments compared 16-day-old and adult mice. Whilst higher gene expression occurred in the parenchyma compared with conducting airways in both groups, significantly greater expression was seen in the conducting airway of adult mice compared with 16-day-old animals. This expression persisted beyond 18 days in the adults but was undetectable in the younger group at this time-point. In an ex vivo model there was no difference in gene expression between the two groups. Further, no differences were observed in gene expression between growing (age 5 weeks to 14 years 8 months) and adult human lung tissue in either parenchyma or conducting airway. These data suggest age-dependent differences in gene transfer in vivo, which are not seen in an ex vivo setting. Proof-of-principle has been demonstrated for cationic-lipid mediated gene transfer to the growing human lung. Gene Therapy (2000) 7, 273-278.

Adolescent↗
PubMed2000

Pulmonary hypertensive diseases.

The commonest causes of pulmonary hypertension are secondary to endstage pulmonary disease or congenital heart disease (including structural abnormalities of the pulmonary veins). Less obvious causes include sleep disordered breathing due to obstructive sleep apnoea or neuromuscular disease, and occult interstitial lung disease. When these have been excluded, the primary pulmonary vascular diseases should be considered. These are primary pulmonary hypertension; pulmonary veno-occlusive disease; pulmonary embolic disease (thromboembolism, and non-thrombotic embolism) and invasive pulmonary capillary haemangiomatosis. The clinical signs and chest X-ray appearances are often non-specific. Echocardiography can often estimate pulmonary artery pressure and exclude congenital heart disease. Right heart catheterization is usually needed to confirm the diagnosis, estimate any reversibility of elevated pulmonary vascular resistance and exclude other causes. Precise diagnosis may require an open lung biopsy. For many of these conditions, treatment is difficult and the prognosis poor unless the child has a lung transplant.

Child↗