Search PubMed⌕ Search

Biomedical subjects

R Yates

Publications and source records attributed to R Yates.

At least 37 records · Page 2Linked to original sources
PubMed2000

Calculating blood flow from Doppler measurements in the systemic-to-pulmonary artery shunt after the Norwood operation: a method based on computational fluid dynamics.

Hypoplastic left heart syndrome is currently the most lethal cardiac malformation of the newborn infant. Survival following a Norwood operation depends on the balance between systemic and pulmonary blood flow, which is highly dependent on the fluid dynamics through the interposition shunt between the two circulations. We used computational fluid dynamic (CFD) models to determine the velocity profile in a systemic-to-pulmonary artery shunt and suggested a simplified method of calculating the blood flow in the shunt based on Doppler measurements. CFD models of systemic-to-pulmonary shunts based on the finite element method were studied. The size of the shunt has been varied from 3 to 5 mm. Velocity profiles at proximal and distal positions were evaluated and correlations between maximum and mean spatial velocity were found. Twenty-one Doppler measurements in the proximal and distal part of the shunt were obtained from six patients with hypoplastic left heart syndrome. Combining Doppler velocities and CFD velocity profiles, blood flow rate in the shunt was calculated. Flow rate evaluated from aortic Doppler and oxygen saturation measurements were performed for comparison. Results showed that proximal shunt Doppler velocities were always greater than the correspondent distal ones (ratio equal to 1.15 +/- 0.11). CFD models showed a similar behaviour (ratio equal to 1.21 +/- 0.03). CFD models gave a V(mean)/V(max) ratio of 0. 480 at the proximal junction and of 0.579 at the distal one. The agreement between the flow evaluated in the proximal and distal areas of the shunt was good (0.576 +/- 0.150 vs. 0.610 +/- 0.166 l/min). Comparison of these data with saturation data and aortic Doppler measurements correlate less well (0.593 +/- 0.156 vs. 1.023 +/- 0.493 l/min). A formula easily to quantify shunt flow rate is proposed. This could be used to evaluate the effects of different therapeutic and pharmacological manoeuvres in this unique circulation.

Anastomosis, Surgical↗
PubMed2000

Dilated cardiomyopathy in dystrophic epidermolysis bullosa.

BACKGROUND: Dystrophic epidermolysis bullosa (DEB) is an uncommon genetic disorder of the skin and mucosae. In 1996, we reported the occurrence of lethal dilated cardiomyopathy (DCM) in two affected children. METHODS: In the past seven years we have routinely screened patients with severe DEB who have been under the care of this hospital by yearly clinical review, echocardiography, and quantification of plasma selenium and carnitine concentrations, as deficiency of these micronutrients is known to be associated with the development of DCM. RESULTS: Six of 61 children have developed DCM over the seven year period of this study, four of whom have not been previously reported, and three of whom have since died. We compared the concentrations of selenium and free and total carnitine in the children who developed DCM to concentrations in those with severe DEB who did not. The concentrations of free and total carnitine when first measured were significantly lower in the children with DCM, but the selenium concentrations were not. CONCLUSIONS: We now believe that DCM is a not infrequent complication of severe recessive DEB, and may be related in part to carnitine concentrations, though the exact mechanism remains unclear. We therefore recommend that patients with this condition should undergo regular cardiac review including echocardiography.

Biomarkers↗
PubMed2000

Mitral valve replacement in children: mortality, morbidity, and haemodynamic status up to medium term follow up.

OBJECTIVE: To investigate the outcome of mechanical mitral valve replacement in children after up to 11 years of follow up. DESIGN: Retrospective analysis of case records. Operative survivors underwent echocardiographic studies to define current haemodynamic status and prosthetic valve function. SETTING: Tertiary referral centre. PATIENTS: All 54 children who underwent mitral valve replacement between January 1987 and December 1997. RESULTS: 30 day mortality was 20.3% and was associated with small valve size and supra-annular position. The actuarial freedom from the following events at five years (70% confidence interval (CI)) was: death, including 30 day mortality and transplantation, 68% (70% CI 62% to 75%); bleeding, 89% (70% CI 84% to 94%); non-structural valve dysfunction and reoperation, 92% (70% CI 87% to 97%). The incidence of endocarditis and thromboembolism was low and there was no structural valve failure. Event-free survival was 52% (70% CI 45% to 60%). Low weight, young age, and small valve size increased the chance of death or reoperation. On echocardiography, left ventricular dilatation and wall motion abnormalities were often observed. A high mean gradient over the prosthesis was associated with small valve size but not with length of follow up. CONCLUSIONS: With the use of mechanical prostheses for mitral valve replacement in children, the problem of structural valve failure is no longer an issue. However, the procedure is still associated with a high complication rate, both at surgery and during follow up, and should therefore be reserved for patients in whom valve repair is not technically feasible.

Adolescent↗
PubMed2000

Quality of life in children following mitral valve replacement.

OBJECTIVE: To measure the health related quality of life (QoL) following mitral valve replacement in childhood. DESIGN: Cross sectional study. SETTING: Tertiary referral centre. METHODS: 19 patients, median age (range) 14.4 (9.7-25.4) years, were studied at a median of 7.6 (0.5-11.2) years after their most recent mitral valve replacement. General health status was measured using age specific validated questionnaires. Ten children aged between 9-15 years completed the child health related quality of life questionnaire, and for nine older patients the UK version of the short form 36 was used. Specific questions were added to the existing questionnaires to study the effect of long term anticoagulation treatment. RESULTS: All patients in the younger age group reported impaired QoL. Five rated their QoL within the range of children with chronic physical disabilities, and in the remaining five it was worse. In the older age group, all but two patients perceived their QoL as normal or near normal compared with a reference population matched for sex and age. Having regular blood tests had a negative effect on QoL in three young children, and one older patient reported impaired QoL related to taking daily warfarin tablets. CONCLUSIONS: In this small group, the effect of mitral valve replacement on QoL appears to be age specific, with more impairment in younger children. Long term anticoagulation treatment is well tolerated in most patients.

Adolescent↗
PubMed1999

Comparison of long-term outcomes of atrial repair of simple transposition with implications for a late arterial switch strategy.

BACKGROUND: We report the single-institution, long-term results of 358 patients with simple transposition of the great arteries surviving >30 days after a Mustard (n=226, 1965 to 1980) or Senning (n=132, 1978 to 1992) procedure. METHODS AND RESULTS: Outcome measures included late death, reintervention, ECG and ambulatory ECG rhythm, new arrhythmia, and functional status. Average follow-up was 13.4 (range 0.32 to 17.9) years for the Senning group and 11.7 (range 0.04 to 23.9) years for the Mustard group. The Senning group had a better survival rate at 5, 10, and 15 years (95% versus 86%, 94% versus 82%, and 94% versus 77%, respectively). In both groups, the majority of late deaths were sudden, without preceding ventricular dysfunction. Survival and survival free of reintervention were significantly better in the Senning group (relative risk [RR] 0.34, P=0.06 versus RR 0.39, P=0.027). Loss of sinus rhythm was comparable and unrelated to death. After era correction, the incidence of atrial flutter was similar and strongly associated with late death in both groups. Clinical systemic ventricular failure was uncommon, and at last follow-up, 92% of the Senning group and 89% of the Mustard group were in New York Heart Association class I. In a model exploring the implications of elective arterial switch conversion, this would only be beneficial if the hazard late after switch was markedly reduced and/or the hazard after the Senning procedure increased with time. CONCLUSIONS: Late outcomes after the Senning procedure are superior to those after the Mustard procedure. Both groups had late sudden deaths that were not associated with clinical systemic ventricular failure. Good functional status after the Senning procedure suggests that a strategy of elective switch conversion cannot be justified for patients with isolated transposition.

Cardiac Surgical Procedures↗
PubMed1999

Persistent pulmonary hypertension of the term neonate: a strategy for management.

UNLABELLED: The management of 32 consecutive term infants referred with persistent pulmonary hypertension of the newborn were reviewed. Despite indices suggesting severe cardiorespiratory failure with a median alveolar-arterial oxygen gradient of 591 torr (inter-quartile range 432-618) and oxygenation index of 31 (18-44), all but one patient responded to conventional treatment with inhaled nitric oxide and high frequency oscillatory ventilation. CONCLUSION: Patients should be referred early to centres where maximal conventional support can be offered before consideration for extracorporeal membrane oxygenation.

Administration, Inhalation↗
PubMed1999

Common arterial trunk associated with double aortic arch.

The combination of common arterial trunk associated with double aortic arch is very rare. We are aware of only four cases ever reported in English literature. We add two cases of this entity and comment on the morphological aspects, the clinical impact of the combined lesions, and their diagnostic and therapeutic implications.

Aorta, Thoracic↗
PubMed1999

Does growth hormone-releasing factor assist follicular development in poor responder patients undergoing ovarian stimulation for in-vitro fertilization?

Treatment with growth hormone-releasing factor (GRF) has been reported to improve the ovarian response to gonadotrophins in women who respond poorly to ovarian stimulation during in-vitro fertilization (IVF). The efficacy and tolerability of GRF were studied in a randomized, double-blind, placebo-controlled trial involving 196 patients. Following down-regulation with a gonadotrophin-releasing hormone agonist (GnRHa), patients were randomized to receive GRF (500 microg twice daily; n = 96) or placebo (n = 100) in addition to follicle stimulating hormone (FSH); treatment was continued until human chorionic gonadotrophin was given, or for a maximum of 14 days. GRF had no significant effect on the mean number of follicles with a diameter of >/=16 mm (GRF: 3.26 +/- 2.29; placebo: 3.27 +/- 2.30; P = 0.95), the number of FSH ampoules required to achieve ovarian stimulation (GRF: 55.2 +/- 16. 4; placebo: 54.9 +/- 17.2; P = 0.50), or on secondary measures of ovarian response and treatment outcome. There were, however, significant increases in circulating growth hormone (GH) and insulin-like growth factor (IGF)-1 concentrations. GRF was well tolerated. It is concluded that, despite producing significant increases in GH and IGF-1, concomitant treatment with GRF does not improve the ovarian response to FSH in poorly responsive women undergoing IVF.

Adolescent↗
PubMed1998

A genetic screen for aminophospholipid transport mutants identifies the phosphatidylinositol 4-kinase, STT4p, as an essential component in phosphatidylserine metabolism.

In an effort to understand molecular mechanisms of intracellular lipid transport, we have focused upon specific events required for de novo aminophospholipid synthesis in the yeast Saccharomyces cerevisiae. A genetic system for examining the steps between phosphatidylserine (PtdSer) synthesis in the endoplasmic reticulum and its transport to and decarboxylation by PtdSer decarboxylase 2 in the Golgi/vacuole has been developed. We have isolated a mutant, denoted pstB1, that accumulates PtdSer and has diminished phosphatidylethanolamine formation despite normal PtdSer decarboxylase 2 activity. The lesion in PtdSer metabolism is consistent with a defect in interorganelle lipid transport. A genomic DNA clone that complements the mutation was isolated, and sequencing revealed that the clone contains the STT4 gene, encoding a phosphatidylinositol 4-kinase. The pstB1 mutant exhibits a defect in Stt4p-type phosphatidylinositol 4-kinase activity, and direct gene replacement indicates that STT4 is the defective gene in the mutant. Creation of an STT4 null allele (stt4Delta::HIS3) demonstrates the gene is essential. These results provide evidence that implicates phosphoinositides in the regulation of intracellular aminophospholipid transport.

1-Phosphatidylinositol 4-Kinase↗
PubMed1998

Rational drug design approach for overcoming drug resistance: application to pyrimethamine resistance in malaria.

Pyrimethamine acts by selectively inhibiting malarial dihydrofolate reductase-thymidylate synthase (DHFR-TS). Resistance in the most important human parasite, Plasmodium falciparum, initially results from an S108N mutation in the DHFR domain, with additional mutation (most commonly C59R or N51I or both) imparting much greater resistance. From a homology model of the 3-D structure of DHFR-TS, rational drug design techniques have been used to design and subsequently synthesize inhibitors able to overcome malarial pyrimethamine resistance. Compared to pyrimethamine (Ki 1.5 nM) with purified recombinant DHFR fromP. falciparum, the Ki value of the m-methoxy analogue of pyrimethamine was 1.07 nM, but against the DHFR bearing the double mutation (C59R + S108N), the Ki values for pyrimethamine and the m-methoxy analogue were 71.7 and 14.0 nM, respectively. The m-chloro analogue of pyrimethamine was a stronger inhibitor of both wild-type DHFR (with Ki 0.30 nM) and the doubly mutant (C59R +S108N) purified enzyme (with Ki 2.40 nM). Growth of parasite cultures of P. falciparum in vitro was also strongly inhibited by these compounds with 50% inhibition of growth occurring at 3.7 microM for the m-methoxy and 0.6 microM for the m-chloro compounds with the K1 parasite line bearing the double mutation (S108N + C59R), compared to 10.2 microM for pyrimethamine. These inhibitors were also found in preliminary studies to retain antimalarial activity in vivo in P. berghei-infected mice.

Animals↗
PubMed1998

Acute hypoxemic respiratory failure in children: case mix and the utility of respiratory severity indices.

OBJECTIVE: Acute hypoxemic respiratory failure (AHRF) is a common reason for emergency pediatric intensive care. An objective assessment of disease severity from acute physiological parameters would be of value in clinical practice and in the design of clinical trials. We hypothesised that there was a difference in the best early respiratory indices in those who died compared with those who survived. DESIGN: A prospective observational study of 118 consecutive AHRF admissions with data analysis incorporating all blood gases. SETTING: A pediatric intensive care unit in a national children's hospital. INTERVENTIONS: None. RESULTS: Mortality was 26/118, 22% (95 % confidence interval 18-26%). There were no significant differences in the best alveolar-arterial oxygen tension gradient (A-aDO2, torr), oxygenation index (OI), ventilation index (VI), or PaO2/FIO2 during the first 2 days of intensive care between the survivors and non-survivors. Only the mean airway pressure (MAP, cm H2O) used for supportive care was significantly different on days 0 and 1 (p < 0.05) with higher pressure being used in non-survivors. Multiple logistic regression analysis did not identify any gas exchange or ventilator parameter independently associated with mortality. Rather, all deaths were associated with coincident pathology or multi-organ system failure, or perceived treatment futility due to pre-existing diagnoses instead of unsupportable respiratory failure. When using previously published predictors of outcome (VI > 40 and OI > 40; A-aDO2 > 450 for 24 h; A-aDO2 > 470 or MAP > 23; or A-aDO2 > 420) the risk of mortality was overestimated significantly in the current population. CONCLUSION: The original hypothesis was refuted. It appears that the outcome of AHRF in present day pediatric critical care is principally related to the severity of associated pathology and now no longer solely to the severity of respiratory failure. Further studies in larger series are needed to confirm these findings.

Acute Disease↗
PubMed1998

Time course of central nervous dopamine-D2 and 5-HT2 receptor blockade and plasma drug concentrations after discontinuation of quetiapine (Seroquel) in patients with schizophrenia.

Quetiapine (Seroquel) is a novel antipsychotic with an atypical profile in animal models and a relatively short plasma half-life of 2.5 5 h. In the present study, we used PET to compare the time course of blockade of dopamine D2 and serotonin 5HT2 receptors of quetiapine using C11-raclopride and C11-N-methyl-spiperone as ligands, parallel to monitoring plasma drug concentrations. It was an open study in 11 schizophrenic men using a fixed dose of 450 mg quetiapine. Eight men completed the 29 days treatment, followed by four PET scans performed over a 26-h period after withdrawal of the compound. Quetiapine was shown to bind to dopamine D2 receptors in striatum and 2 h (t[max]) after the last dose, 44% receptor occupancy was calculated. After 26 h it had dropped to the same level as was found in untreated healthy volunteers. Serotonin 5HT2 receptor blockade in the frontal cortex was 72% after 2 h, which declined to 50% after 26 h. The terminal plasma half-life of quetiapine was 5.3 h. Clinically, our eight patients had good antipsychotic effect without any extrapyramidal side-effects. Our data shows that quetiapine has a relatively low affinity for dopamine D2 receptors, with an occupancy half-life (10 h), which was about twice as long as that for plasma. A more prolonged blockade of the serotonin 5HT2 receptors was found in the frontal cortex, with receptor occupancy half-life of 27 h. Compared to clozapine, as demonstrated in other studies, quetiapine has much the same ratio of D2/5HT2 occupancy. This could suggest that the combination of D2/5HT2 receptor blockade contributes to the antipsychotic effect and a low incidence of EPS seen with quetiapine in comparative phase three trials. Our results also confirm the clinical data that quetiapine can be administered twice daily.

Adult↗
PubMed1998

The effects of a potassium citrate, cetylpyridinium chloride, sodium fluoride mouthrinse on dentine hypersensitivity, plaque and gingivitis. A placebo-controlled study.

Home-use studies on dentine hypersensitivity have most commonly involved toothpastes and rarely have mouthrinses been employed. Potassium and/or fluoride toothpastes have been shown effective in the treatment of dentine hypersensitivity. The aim of this study was to evaluate the effectiveness of a total formulation, containing potassium citrate, sodium fluoride, cetylpyridinium chloride mouthrinse compared to the base rinse minus actives in the reduction of dentine hypersensitivity. The study was a randomised placebo controlled, double blind parallel design. At a screening visit, 90 adult subjects were recruited who were suffering from dentine hypersensitivity from at least 1 tooth responding to tactile stimulation (45gm pressure) and had at least 2 teeth responding to evaporative stimulation (air blast). During a washout period of 28 days and throughout the 56-day study period, subjects used a soft filament toothbrush and standard fluoride toothpaste. At baseline (day 1), threshold sensitivities to incremental tactile (10 g to 70 g) and evaporative stimuli were determined. Gingival health was assessed by recording bleeding on probing at 25 g pressure at mesiobuccal and lingual sites. Plaque scores from buccal and lingual surfaces of disclosed teeth were also measured. Subjects then used the prescribed rinse, 10 ml for at least 30 s after brushing 2x per day returning on days 28 and 56 for rescoring of sensitivity, gingivitis and plaque. Data from 88 subjects were used with the intent to treat analyses and 83 in the completely evaluable analyses. Groups were well balanced for demographic data and product returns suggested good compliance. Both groups showed highly significant improvements in tooth sensitivity. The pattern was for greater improvement in the test compared to the control group (statistically significant for the plaque score), whereas bleeding scores, already low, showed no change in either group. By definition, the placebo rinse could not have exerted any therapeutic action; the study therefore provides clear direct evidence as to the magnitude (30%-40%) of the little studied, but assumed, placebo response in dentine hypersensitivity trials.

Adolescent↗
PubMed1998

A split-mouth placebo-controlled study to determine the effect of amorphous calcium phosphate in the treatment of dentine hypersensitivity.

Many treatments for dentine hypersensitivity are formulated to directly or indirectly occlude the open dentinal tubules associated with the condition. Combining solutions of calcium chloride and potassium phosphate can result in the precipitation of amorphous calcium phosphate. Such a system applied to exposed dentine could occlude dentinal tubules and reduce sensitivity. The aims of this study using a placebo control were to assess the therapeutic value of amorphous calcium phosphate in dentine hypersensitivity and provide further information on the apparently natural improvement in the condition frequently observed in clinical trials. 38 subjects with dentine hypersensitivity affecting 1 tooth in each left and right sides of the jaws were recruited into this split mouth, randomised, double-blind study. At baseline, sensitivity was scored by the subjects on a 0-10 visual apologue scale after tactile, cool and cold water and evaporative stimulation of the test teeth. Active and control, water, solutions were then applied by a 2nd clinician. After 24 h, subjects returned for rescoring. On days 7 and 14, subjects were again rescored and the treatments reapplied. Further follow-up appointments for rescoring were on days 21, 28, 56 and 84. Plaque scores also were recorded from test teeth at each visit. Overall sensitivity decreased considerably and to a similar degree in test and control teeth with no consistent significant treatment difference. Plaque scores also decreased through the study period. It is concluded that either the amorphous calcium phosphate was without therapeutic effect or the activity was masked by the placebo response in the control teeth.

Administration, Topical↗