Dopamine agonist therapy in early Parkinson's disease.

BACKGROUND: Dopamine agonists are being used increasingly as first line treatment for Parkinson's disease, but there remains uncertainty about their clinical and cost-effectiveness relative to levodopa. OBJECTIVES: This meta-analysis aims to quantify more reliably the benefits and risks of dopamine agonists compared to placebo or levodopa in early Parkinson's disease. SEARCH STRATEGY: We searched CENTRAL (The Cochrane Library), MEDLINE, EMBASE, PubMed, LILACS and Web of Science, plus major journals in the field, abstract books, conference proceedings and reference lists of retrieved publications. SELECTION CRITERIA: Randomised trials comparing an orally administered dopamine agonist (with or without levodopa) versus placebo or levodopa or both placebo and levodopa in participants with early Parkinson's disease. DATA COLLECTION AND ANALYSIS: Two authors independently extracted data on clinician-rated disability, motor complications, other side-effects, treatment concordance, levodopa dose and mortality. MAIN RESULTS: Twenty-nine eligible trials, involving 5247 participants, were identified. Participants randomised to a dopamine agonist were less likely to develop dyskinesia (odds ratio (OR) 0.51, 95% confidence interval (CI) 0.43 to 0.59; P < 0.00001), dystonia (OR 0.64, 95% CI 0.51 to 0.81; P = 0.0002) and motor fluctuations (OR 0.75, 95% CI 0.63 to 0.90; P = 0.002) than levodopa-treated participants. However, various 'non-motor' side-effects, including oedema (OR 3.68, 95% CI 2.62 to 5.18; P < 0.00001), somnolence (OR 1.49, 95% CI 1.12 to 2.00; P = 0.007), constipation (OR 1.59, 95% CI 1.11 to 2.28; P = 0.01), dizziness (OR 1.45, 95% CI 1.09 to 1.92; P = 0.01), hallucinations (OR 1.69, 95% CI 1.13 to 2.52; P = 0.01) and nausea (OR 1.32, 95% CI 1.05 to 1.66; P = 0.02) were all increased in agonist-treated participants (compared with levodopa-treated participants). Agonist-treated participants were also significantly more likely to discontinue treatment due to adverse events (OR 2.49, 95% CI 2.08 to 2.98; P < 0.00001). Finally symptomatic control of Parkinson's disease was better with levodopa than with agonists, but data were reported too inconsistently and incompletely to meta-analyse. AUTHORS' CONCLUSIONS: This meta-analysis confirms that motor complications are reduced with dopamine agonists compared to levodopa, but also establishes that other important side-effects are increased and symptom control is poorer with agonists. Larger, long-term comparative trials assessing patient-rated quality of life are needed to assess more reliably the balance of benefits and risks of dopamine agonists compared to levodopa.

Operation Open Heart in PNG, 1993-2006.

OBJECTIVE: To report on the 'Operation Open Heart' (OOH) cardiac surgical program in Papua New Guinea (PNG). To document the short-term surgical outcome, the experience gained and the skill transfer from the visiting team members to their PNG counterparts. METHODOLOGY: Analysis of the database compiled from the records of the patients who were operated on by the visiting cardiothoracic surgical team. RESULTS: Four hundred and seventy patients from all regions of the country received operations. Three hundred and thirty seven (72%) were children less than 12 years of age, 39 (8%) were between 12 and 18 years of age and 263 (56%) were females. One hundred and eighty five (40%) patients had open heart procedures. Complications were unremarkable and the short-term mortality was 1.9%. Clinical skills were transferred to, and experience was gained by national anaesthetists, surgeons, paediatricians, physicians and nurses from intensive and full nursing care units and the operating theatre. CONCLUSIONS: The program not only achieved a higher annual operation rate than previous programs but also had a lower mortality rate. It achieved its objective of service delivery and, to a considerable extent, its objective of skill transfer. There now is an established and active group of PNG doctors and nurses with the skills, experience and confidence to perform patent ductus repair safely and efficiently. The program is cheaper than its predecessors, and is less disruptive for parents, patients and families.

Coronary artery fistula in a patient with pulmonary atresia and tricuspid atresia clinical and MRI findings.

The MRI findings of a case of coronary artery fistula occurring in a patient with pulmonary atresia and tricuspid atresia is presented.

Late aortic root dilatation in tetralogy of Fallot may be prevented by early repair in infancy.

The objectives of this study were to examine the relative contributions of development and hemodynamics in aortic root dilatation of tetralogy of Fallot, to assess the impact of systemic to pulmonary artery shunt on aortic annular size, and to seek any relationship between the timing of corrective surgery and subsequent aortic root size. We performed a retrospective analytical study at a tertiary referral center of M-mode and two-dimensionol aortic root measurements in children with tetralogy of Fallot prior to any surgical or palliative intervention, after insertion of a surgical shunt, and on intermediate and long-term follow-up post-repair. The main outcome measures were aortic root diameter prior to correction, after palliative shunt insertion, and after definitive repair. The study found that the aortic root is enlarged in unrepaired tetralogy of Fallot irrespective of age, increased in the first 3-6 months after palliative shunt surgery, and persisted into adulthood in those repaired after 1 year of age. Age-corrected aortic root dimensions normalized by mid-childhood in those who were repaired in infancy. Preexisting aortic root dilatation normalizes by 7 years of age in patients with tetralogy of Fallot who have been repaired in infancy, whereas it persists into adulthood in the group repaired post-infancy.

Surgical programme at Royal Alexandra Hospital, Sydney, for Papua New Guinea children with congenital heart disease, 1978-1994.

OBJECTIVE: To report the history of the Royal Alexandra Hospital for Children (RAHC) Papua New Guinea (PNG) cardiac surgical programme and describe the selection, preoperative clinical features and postoperative outcome of children with congenital heart disease managed by the programme. METHODS: Details for each of the PNG cardiac patients admitted to RAHC following selection by visiting cardiologists between 1978 and 1994 were entered into a database, and analysed and interpreted. RESULTS: A congenital heart defect was confirmed in 165 of the 170 children selected. The male to female ratio was 1:1 and the mean age on admission to RAHC was 5.5 years. Almost all of the children for whom data were available (98%) had a weight for age and 41% had a height for age less than the 3rd centile. One-sixth had delayed milestones. A large number were tachypnoeic, in heart failure, or had pulmonary hypertension on admission. Ventricular septal defect and tetralogy of Fallot were the commonest defects, and lesions such as aortic stenosis, coarctation of the aorta and transposition of the great arteries were absent or rare. Thirty-one (19%) of the children selected initially did not receive surgery because of pulmonary hypertension, or because the lesions did not fall within the programme guidelines for operation. One hundred and twenty-nine children had corrective and four had palliative procedures. Half of the operated children had postoperative complications. Eight children died, all following open-heart procedures, giving a case fatality rate of 6%. Preoperative tachypnoea, hepatomegaly, cardiac failure and pulmonary hypertension were strongly associated with poor outcome. CONCLUSIONS: The programme was an arduous exercise for all organizations concerned, but achieved comparatively good short-term outcomes. The experience gained should assist in planning for similar programmes.

Congenital heart disease in Papua New Guinean children.

The aim of the study was to analyse critically the programme for surgical management of children in Papua New Guinea (PNG) with congenital heart disease. A hospital record-based analysis was undertaken to document the pattern, management and short-term outcome of surgery in PNG children referred with a diagnosis of congenital heart disease to the Royal Alexandra Hospital for Children in Sydney, Australia. On admission, physical examination, chest radiogram, electrocardiogram, cross-sectional echocardiogram and, in most cases, cardiac catheterization were performed. Of the 170 children referred over the 17-year period, 1978-1994, 165 were confirmed to have congenital heart disease and were included in the study. Their ages ranged from 2 months to 16 years (median 5.5) and the male to female ratio was 1:1. One-sixth had delayed milestones and one-fifth long-term wasting. A large number were tachypnoeic, in heart failure or had pulmonary hypertension on admission. Ventricular septal defect, 34%, tetralogy of Fallot, 23%, and patent ductus arteriosus, 16.4%, were the predominant defects. lesions such as aortic stenosis, coarctation of the aorta and transposition of the great arteries are under-represented. Altogether, 133 children (81%) had surgery; 75% were open- and 25% closed-heart operations. The complications were unremarkable and the mortality rate (6%) acceptable for the era. The programme was therefore very successful for a small proportion of children born in PNG with congenital heart disease.

Influences of pH on human platelet metabolism.

The intracellular pH of human platelets is affected by external pH and by the addition of metabolic substrates and analogues. Acetate and propionate decrease pH in a rapid concentration-dependent manner, whereas glucose decreases the internal pH at a slower rate which is independent of concentration above 0.3 mM. The mechanisms of these effects is discussed. The rate of metabolism of glucose to lactate in human platelets was strongly pH-dependent, with higher rates at more alkaline pH values. This effect was found for several different buffer systems. Addition of acetate caused an inhibition of glycolysis, whereas addition of propionate had little effect. The rate of the oxidative pentose phosphate pathway also increased with increasing pH and this pathway was inhibited by both acetate and propionate. It is proposed that the effect of acetate on glycolysis required the metabolism of the acetate, whereas the effect of both acetate and propionate on the pentose phosphate pathway are directly due to the decrease in internal pH. The oxidation of acetate to carbon dioxide showed only small pH-dependent changes in rate unless glucose was also present: glucose inhibited oxidative metabolism (the 'Crabtree Effect'), but this inhibition was only apparent at higher pH values when glycolytic rates were high.

Role of ischemia and infarction in late right ventricular dysfunction after atrial repair of transposition of the great arteries.

OBJECTIVES: This study was conducted to assess whether myocardial ischemia and/or infarction are involved in the pathogenesis of late right ventricular dysfunction in adult survivors of atrial baffle repair for transposition of the great arteries in infancy. BACKGROUND: The medium-term success of intraatrial baffle repair for transposition of the great arteries is good, with many patients surviving into adult life, but prognosis can be limited by progressive right ventricular dysfunction. We hypothesized that ongoing myocardial ischemia and/or infarction are important factors in the pathogenesis of this complication. Radionuclide techniques offer an opportunity to study both myocardial perfusion and concomitant ventricular wall motion. METHODS: Dipyridamole sestamibi single-photon emission computed tomography followed by rest sestamibi single-photon emission computed tomography was used to assess right ventricular myocardial perfusion, wall motion, wall thickening and ejection fraction in 22 adolescents/young adults who had undergone atrial baffle repair for simple transposition of the great arteries at median 6.7 (range 0.5 to 54) months of age. The patients were aged 10 to 25 (median 15.5) years; 19 in New York Heart Association class I, 2 in class II and 1 in class III. All were in a regular cardiac rhythm during the studies. The right ventricular tomographic images were examined in three parallel and two orthogonal planes, analyzed in 12 segments. RESULTS: Perfusion defects were evident in all patients in at least one segment, in either the rest or stress images. Twelve patients (55%) demonstrated fixed defects only, nine (41%) had fixed and reversible defects and one (4.5%) had reversible defects only. Concomitant wall-thickening abnormalities occurred in 83% of segments with fixed perfusion defects, mirrored by a reduction in wall motion in 91% of segments analyzed. Right ventricular ejection fraction was correlated with age (R = 0.62; p = 0.002), and with wall-thickening abnormalities (R = 0.60; p < 0.005). CONCLUSIONS: Reversible and fixed perfusion defects with concordant regional wall motion abnormalities occur in the right (systemic) ventricle 10 to 20 years after Mustard repair for transposition of the great arteries; this may be important in the pathogenesis of late right ventricular dysfunction in this group.

A history of surgery for congenital heart disease in Papua New Guinea.

Cardiothoracic surgery in Papua New Guinea (PNG) was somewhat ad hoc prior to 1956 but later settled into an arrangement in which visiting teams from overseas selected mostly adult patients for a limited range of closed heart operations to be done locally or overseas. In 1978 the late Professor John Biddulph was instrumental in facilitating a more formal arrangement with the Royal Prince Alfred Hospital whereby patients were selected by a visiting cardiologist on an annual basis to be transferred to Sydney for cardiac surgery. This subsequently developed into a predominantly paediatric program based at the Royal Alexandra Hospital for Children in Sydney, which successfully ran until 1992. In 1993 a program began, based at the Sydney Adventist Hospital, in which a voluntary cardiac team has been visiting annually to perform both open and closed heart surgery. This program has proved to be very successful with a high output and a low mortality. Despite this long history of surgery for congenital heart disease in PNG, no definite long-term plans have eventuated. Because the financial situation of the country does not allow for a major cardiothoracic unit, the current arrangement whereby noninvasive investigation and some closed surgery are performed at Port Moresby General Hospital is appropriate for the foreseeable future.

Right ventricular dysfunction in congenitally corrected transposition of the great arteries.

Although right ventricular (RV) dysfunction is an important complication in subjects with congenitally corrected transposition of the great arteries, its pathogenesis is poorly understood. We assessed the role of RV myocardial perfusion and found perfusion defects at rest in all 20 patients, involving 4.6 +/- 2.3 of a total of 12 segments; the extent of the resting perfusion defects correlated inversely with the RV ejection fraction.

Simplified single patch technique for the repair of atrioventricular septal defect.

OBJECTIVE: Because of the complexity of traditional 1- and 2-patch techniques for the repair of complete atrioventricular septal defect, we modified our repair technique to avoid the use of any ventricular septal patch material. We report our prospective experience with this simplified 1-patch technique. METHOD: Forty-seven consecutive patients between May 1995 and August 1998 underwent repair with the use of this technique without modification. Repair was done in all patients by direct suturing of the common atrioventricular valve leaflets to the crest of the ventricular septum. No division of valve leaflets was necessary. A single pericardial patch was used to close the defect in the atrial septal component. Follow-up included electrocardiography and echocardiographic assessment of ventricular function, atrioventricular valve function, and adequacy of the left ventricular outflow tract. RESULTS: There were 2 deaths (4%), only 1 cardiac related, in the series. There were 17 male patients and 30 female patients. Mean age at repair was 5.6 months (median, 3.4 months). Associated lesions were repaired in 19 patients (40%). Mean follow-up was 1.85 years (median, 1.9 years). There was no heart block. There were no significant residual ventricular septal defects detected and no left ventricular outflow tract obstruction seen on echocardiography in any patient to date. Mitral valve status after operation was assessed as no incompetence in 13 patients (28%), minimal in 19 patients (40%), mild in 12 patients (26%), and moderate in 3 patients (6%). CONCLUSION: The repair of complete atrioventricular septal defect by direct suturing of the atrioventricular valve leaflets to the crest of the ventricular septum with a single-patch technique greatly simplifies the repair and does not lead to left ventricular outflow tract obstruction nor interfere with valve function.

Branch pulmonary artery growth after blalock-taussig shunts in tetralogy of fallot and pulmonary atresia with ventricular septal defect: a retrospective, echocardiographic study.

We performed a retrospective echocardiographic study in tetralogy of Fallot (TOF) or pulmonay atresia with ventricular septal defect (PA&VSD) to evaluate the effects of Blalock-Taussig shunt on branch pulmonary artery growth. There were 35 patients with TOF and 11 with PA&VSD. We measured the right and left pulmonary artery area index and also the combined pulmonary artery area index, both before and after shunt operation. The mean +/- SD of these three variables before the shunt operation in the TOF group were 63.5 +/- 22.5, 57.8 +/- 24.9, and 121.4 +/- 42.8 mm(2)/m(2); after shunt operation they were 98.5 +/- 33.6, 85.9 +/- 31.9, and 184.0 +/- 59.8 mm(2)/m(2), respectively (p values <0.0001, <0.0002, and <0.0001, respectively). In the PA&VSD group the comparable values before shunt operation were 66.5 +/- 16.0, 55.4 +/- 10.6, and 120.9 +/- 26.9 mm(2)/m(2) and after shunt operation were 90.5 +/- 22.9, 77.2 +/- 24.1, and 166.6 +/- 44.4 mm(2)/m(2), respectively (p values <0.0006, <0.014, and <0. 002, respectively). We also examined the effect of distensibility of pulmonary arteries by comparing the percentage change in size of the combined pulmonary artery area index in the first 4 months after shunt with those after this time (p < 0.023). There were no significant differences between left- and right-sided shunts, origin and distal pulmonary artery growth, and the TOF and PA&VSD groups.

Radiofrequency catheter ablation of right ventricular outflow tract tachycardia in a preschooler.

A 3-year-old girl presented with a febrile illness complicated by right ventricular outflow tract tachycardia, which persisted after resolution of the presumed viral infection. The tachycardia was intermittent, but was significantly exacerbated by exercise. Radiofrequency ablation (RFA) of the ectopic focus was successfully performed and the child remains free of tachycardia 12 months later. A review of the literature suggests that RFA in children is increasingly seen as a safe and convenient option for the treatment of supraventricular tachycardia, whereas the management of ectopic ventricular tachycardia in pediatric practice has not been well defined.

Neonatal ductus arteriosus aneurysm causing nerve palsies and airway compression: surgical treatment by decompression without excision.

A 4-kg male child, born at 34 weeks to a gestational diabetic mother, had a large ductus arteriosus aneurysm causing phrenic and recurrent laryngeal nerve palsies and large airway compression. The right and left atrial appendages and distal descending aorta were cannulated, allowing left heart partial or complete cardiopulmonary bypass as necessary. On bypass the ductus was ligated, decompressed, and oversewn but not excised. Examination 1 month later suggested resolution of the recurrent laryngeal palsy and echocardiography showed regression of the aneurysm. Ductus ligation and decompression was an effective surgical treatment, which is less likely to cause complications than resection.

Inhibition of phenolsulphotransferase by salicylic acid: a possible mechanism by which aspirin may reduce carcinogenesis.

BACKGROUND: Recent epidemiological evidence has shown that chronic use of aspirin decreases susceptibility to bowel cancer. Animal studies have shown that sulphotransferase inhibitors coadministered with sulphation activated carcinogens dramatically reduce the incidence of cancer. AIMS: To investigate the effect of the main aspirin breakdown product, salicylic acid, on the P and M isoforms of phenolsulphotransferase from human platelets and colonic mucosa. METHODS: Platelets were obtained from healthy blood donors and isolated within 24 hours after donation. Samples of colonic mucosa were obtained at resection for non-malignant disease. Phenolsulphotransferase activity was measured in cellular homogenates using a standard radiolabelling assay. RESULTS: Salicylic acid consistently and selectively inhibited the P form of phenolsulphotransferase at subtherapeutic concentrations in both tissue samples. A 50% inhibition of sulphation by the P phenolsulphotransferase occurred at salicylic acid concentrations of about 40 and 130 microM in platelets and bowel mucosa respectively. M phenolsulphotransferase was virtually unaffected by salicylic acid up to a concentration of 1.5 mM (the therapeutic plasma concentration for salicylates when treating rheumatoid arthritis is about 1-2 mM). CONCLUSION: The action of salicylic acid on P phenolsulphotransferase, by preventing the excessive activation of carcinogens, is a possible additional pathway by which aspirin can reduce cancer risk.

Myocardial perfusion defects and associated systemic ventricular dysfunction in congenitally corrected transposition of the great arteries.

BACKGROUND: Patients with systemic ventricles of right ventricular morphology are at high risk of contractile dysfunction, the cause of which has not been fully elucidated. OBJECTIVE: To assess whether ischaemia or infarction contributes to ventricular impairment in unoperated patients with uncomplicated congenitally corrected transposition of the great arteries (TGA) by studying myocardial perfusion and function. SETTING: Paediatric and adult congenital cardiac clinics of a tertiary referral centre. PATIENTS: Five patients with congenitally corrected TGA but without associated structural cardiac defects (aged 3.5 to 34 years). INTERVENTIONS: Maximal exercise stress testing using standard or modified Bruce protocols. Sestamibi (technetium-99m methoxy isobutyl isonitrile) scanning after isotope injection at maximal exercise and rest. MAIN OUTCOME MEASURES: Maximum exercise capacity; right ventricular myocardial perfusion, regional wall motion, and thickening; right ventricular ejection fraction. RESULTS: The two youngest patients (3.5 and 11 years) had normal exercise capacity for age, while the others had reduced exercise performance. Sestamibi scanning showed reversible myocardial ischaemia in four patients and fixed defects indicating infarction in five. Irreversible defects were mostly associated with impaired wall motion and thickening. The ejection fraction was normal (65%) in the youngest patient but < 55% in the others (mean (SD) 47(11)%). CONCLUSIONS: Patients with unoperated congenitally corrected TGA have a high prevalence of myocardial perfusion defects, with consequent abnormalities of regional wall motion and thickening, and impaired ventricular contractility. These data suggest that ischaemia and infarction are important in the pathogenesis of ventricular failure in this condition.

Citrate metabolism by human platelets.

As part of a study on the utilization of substrates by platelets in defined media the metabolism of citrate was measured, since citrate is a common anticoagulant of nearly all such media, and is also an intermediate of oxidative metabolism. Human platelets transferred from plasma to an artificial medium by gel filtration, were incubated with [14C]citrate at 22 degrees C and labelled carbon dioxide produced was measured during short-term incubations of 2 h. Citrate (1 mM) was oxidized to carbon dioxide at low (0.3 nmol per 10(9) platelets h-1) but significant rates, and the oxidation was decreased by the presence of an alternative substrate (acetate) in the medium. There was, however, no significant conversion of citrate to glycogen. It was calculated that under normal storage conditions of platelet concentrates for transfusion purposes, the amount of citrate used cannot decrease citrate concentrations sufficiently to bring about platelet activation.