Electrographic Correlates of Plateau Waves in Patients With Leptomeningeal Metastases.

We describe video electroencephalography (video-EEG) correlates of transient neurological attacks due to plateau waves-paroxysmal elevations in intracranial pressure-in patients with leptomeningeal metastases. We identified 3 patients with leptomeningeal metastases, intracranial hypertension, and transient neurological attacks captured on video-EEG without evidence of seizures or epileptiform activity. We identified all clinical events on video and reviewed the corresponding EEG data for evidence of abnormalities. All 3 patients had mild to moderate slowing and 2 had frontal intermittent rhythmic delta activity during background EEG recording. There were 33 clinical events recorded and stereotyped for each patient. All 33 events were associated with an increase in delta range slowing of ≥30% compared to the background. This abnormality started ≤2 minutes before the onset of clinical symptoms and persisted for minutes after clinical resolution. This study is the first to carefully describe the electrographic correlates of transient neurological attacks due to plateau waves in patients with leptomeningeal metastasis. Clinical attacks were consistently associated with a possible EEG signature of diffuse delta range slowing. Future studies can validate the sensitivity and specificity of these EEG changes as a prognostic and/or response biomarker in patients with leptomeningeal metastases with or without intracranial hypertension.

Anti-myelin antibodies modulate clinical expression of childhood multiple sclerosis.

Anti-myelin basic protein (MBP) antibodies in pediatric-onset MS and controls were characterized. Serum samples were obtained from 94 children with MS and 106 controls. Paired CSF and serum were obtained from 25 children with MS at time of their initial episode of acute demyelinating syndrome (ADS). Complementary assays were applied across samples to evaluate the presence, and the physical binding properties, of anti-MBP antibodies. While the prevalence and titers of serum anti-MBP antibodies against both immature and mature forms of MBP were similar in children with MS and in controls, binding characteristics and formal Surface Plasmon Resonance (SPR) studies indicated surprisingly high binding affinities of all pediatric anti-MBP antibodies. Serum levels of anti-MBP antibodies correlated significantly with their CSF levels, and their presence in children with MS was associated with significantly increased risk of an acute disseminated encephalomyelitis-like initial clinical presentation. While antibodies to both immature and mature forms of MBP can be present as part of the normal pediatric humoral repertoire, these anti-myelin antibodies are of surprisingly high affinity, can access the CNS during inflammation, and have the capacity to modulate disease expression. Our findings identify an immune mechanism that could contribute to the observed heterogeneity in spectrum of clinical presentations in early-onset MS.

Asymptomatic fatal post-lobectomy hemopericardium.

We report a case of an asymptomatic post-lobectomy hemopericardium in a female who died suddenly at day two post surgery. Autopsy revealed no pathologic findings, but 250 ml of blood and clots in the pericardium and a non-significant injury to the epicardial fat overlying the circumflex artery territory.

Good outcomes from cardiac surgery in the over 70s.

OBJECTIVE: To determine the early mortality and major morbidity associated with cardiac surgery in the elderly. DESIGN: Retrospective case record review study of 575 patients >/= 70 years old who underwent cardiac surgery at the Manchester Heart Centre between January 1990 and December 1996. SETTING: Regional cardiothoracic centre. SUBJECTS: Patients >/= 70 years old who underwent cardiac surgery. MAIN OUTCOME MEASURES: Comparison of 30 day mortality and incidence of major morbidity between patients >/= 70 years old and patients < 70 years old. RESULTS: Of 4395 cardiac surgical operations, 575 operations (13.1%) were in patients aged >/= 70 years (mean (SD) 73.1 (3.2) years). The proportion of elderly patients rose progressively from 7.9% in 1990 to 16.5% in 1996. 334 patients (58.1%) had coronary artery bypass grafting alone, 91 patients (15.8%) had valve surgery alone, and 129 patients (22.4%) had combined valve surgery and bypass grafting. For isolated coronary artery bypass grafting, 30 day mortality in patients >/= 70 years was 3.9% compared with 1.3% in patients < 70 years (p < 0.001). 30 day mortality for isolated valve surgery in patients >/= 70 years was 7.7%. Isolated aortic valve replacement was the most common valvar procedure in patients >/= 70 years and carried the lowest mortality (4.3%). Additional coronary artery bypass grafting increased the mortality rate in patients >/= 70 years to 9.3% for all valve surgery and to 8.0% for aortic valve replacement. Major morbidity in patients >/= 70 years was low for all procedure types (stroke 1.9%, acute renal failure requiring dialysis 1.6%, perioperative myocardial infarction 0.5%). CONCLUSIONS: Early mortality and major morbidity is low for cardiac surgery in elderly patients. Concerns over the risk of cardiac surgery in the elderly should not prevent referral, and elderly patients usually do well. However, unconscious rationing of health care may affect referral patterns, and studies that assess the cost effectiveness of cardiac surgery versus conservative management in such patients are lacking.

A pilot study of blood antioxidant and free radical marker profiles in patients awaiting coronary artery bypass grafting.

Coronary artery bypass grafting (CABG) carries a high risk of acute pancreatitis. We report a pilot study to investigate whether pre-existing oxidative stress might underlie this susceptibility, in that a burst of free radical activity not only accompanies the reperfusion stage of CABG but seems to be a pivotal step in the pathogenesis of pancreatitis. Samples of peripheral venous blood were obtained on the morning of surgery from 8 consecutive patients (age, median and range, 62, 35-70 years) with > 75% stenosis in at least three coronary vessels and a further 8 (64, 49-70 years) who had received 1200 mg allopurinol in divided doses in the previous 48 h: the results were compared with profiles of 8 healthy controls (56, 50-60 years) with normal exercise ECG. None of the patients or controls currently smoked cigarettes and the majority drank alcohol on a social basis. Compared with controls, untreated patients had lower levels of glutathione (P < 0.001) and ascorbate (P < 0.05) in plasma, alpha-tocopherol (vitamin E as molar ratio of cholesterol, P < 0.025 and beta-carotene (P < 0.05) in serum. There was no difference in serum selenium levels, but values in patients and controls were lower than in younger controls from this area (P < 0.02). Samples from the patients contained higher concentrations of lipid peroxides than control samples (P < 0.25) but there was no evidence of excessive isomerisation of linoleic acid or oxidation of ascorbate and erythrocytes showed normal ATP and energy charge with no increase in membrane lipid peroxidisability. Treatment with allopurinol did not alter this pattern, such that the ratio of oxidised to total glutathione in plasma was higher among the 16 patients than 8 controls (P < 0.025). Habitually inadequate intakes are the best explanation for the patients' deficits in aqueous phase antioxidants; prescribed low cholesterol diets would exacerbate any prior insufficiency of lipid-phase antioxidants. Correction of these deficits during the months leading up to surgery should reduce the risk of CABG-induced acute pancreatitis.

Comparison of saccharides as osmotic impermeants during hypothermic lung graft preservation.

We have previously shown that the trisaccharide raffinose is largely responsible for the superior lung graft performance seen after storage in University of Wisconsin solution. To investigate the use of osmotic agents in perfusates for hypothermic lung graft storage, we compared saccharides of various molecular weights in an isolated rat lung model. Grafts were flushed with 1 of 6 preservation solutions (n=5 each group) containing either a monosaccharide (glucose [G] or fructose [F]), disaccharide (trehalose [T] or sucrose [S]), or trisaccharide (raffinose [R] or melezitose [M]. Grafts were stored for 6 hours at 4 degrees C, reperfused by a veno-venous circuit from an anesthetized support animal for 60 min, and ventilated with room air. The best graft function was seen when trisaccharides were used (PO2; R 126 +/- 3 mm Hg, M 129 +/- 3 mm Hg, blood flows: R 10.2 +/- 0.42 ml/min, M 10.3 +/- 0.22 ml/min). Disaccharides produced similar oxygenation (T 133 +/- 3 mm Hg, S 129 +/- 3 mm Hg) and flows (T 10.3 +/- 0.29 ml/min, S 9.7 +/- 0.4 ml/min) at 60 min, but initial flows were reduced. Monosaccharides produced the least satisfactory graft function, with impaired oxygenation (F 110 +/- 14 mm Hg, P<0.05; G 69 +/- 10 mm Hg, P<0.01) and blood flows (G 6.5 +/- 0.6 ml/min, F 9.1 +/- 0.6 ml/min, P<0.01 each). Only glucose-stored lungs demonstrated a significant decrease in compliance (P<0.01) and weight gain (P<0.01). The worst results were seen with glucose, which is the osmotic agent most commonly used for clinical lung storage. A solution containing a trisaccharide or disaccharide may be more appropriate for this purpose.

Controlled pressure reperfusion of rat pulmonary grafts yields improved function after twenty-four-hours' cold storage in University of Wisconsin solution.

BACKGROUND: Pulmonary graft recipients commonly have a degree of pulmonary hypertension. Immediate reperfusion of stored pulmonary grafts at supraphysiologic or even physiologic pressures may be detrimental to subsequent function. We wished to test the hypothesis that initial reperfusion of pulmonary grafts at low pressures may be beneficial. METHODS: We used an isolated, ventilated rat lung model, perfused by an extracorporeal veno-venous circuit from a support animal. Three groups of donor lungs (n = 5 each) were flushed with cold University of Wisconsin solution. Group I was reperfused immediately at physiologic pressure to provide control values. Group II grafts were stored at 4 degrees C for 24 hours and reperfused at physiologic pressure. Group III grafts were also stored at 4 degrees C for 24 hours but reperfused according to a protocol of reduced pressure initially, with increments every 15 minutes up to physiologic levels by 60 minutes. Grafts and support animals were ventilated with room air. Graft function was assessed over a 2-hour period with regard to oxygenation, vascular resistance, peak airway pressure, and the wet/dry weight ratio. RESULTS: Grafts in group II functioned poorly at 2 hours compared with control values: group II: oxygen tension 68 +/- 4 mm Hg; pulmonary vascular resistance 2488 +/- 675 x 10(3) dyne.sec/cm5; peak airway pressure 32 +/- 1 mm Hg wet/dry wright ratio 9.1 +/- Group I: oxygen tension 136 +/- 2 mm Hg; pulmonary vascular resistance 120 +/- 3 x 10(3) dyne.sec/cm5; peak airway pressure 13 +/- 1 mm Hg and wet/dry weight ratio 3.6 +/- 0.3; p < 0.001 all parameters except pulmonary vascular resistance: p < 0.05. In contrast, grafts undergoing controlled pressure reperfusion (group III) achieved function comparable with baseline values at 2 hours: oxygen tension 137 +/- 3 mm Hg; pulmonary vascular resistance 132 +/- 7 x 10(3) dyne. sec/cm5; peak airway pressure 13 +/- 1 mm Hg; wet/dry weight ratio 4.1 +/- 0.3 (p = Not significant). CONCLUSIONS: The pressure at which pulmonary grafts are initially reperfused appears to be critical to their subsequent integrity. A protocol of controlled reperfusion may reduce reperfusion injury and improve graft function in clinical practice.

A technique for studying the function of an isolated, perfused and ventilated lung in a rat model.

We describe a technique which allows perfusion of an isolated, ventilated rat lung with an extracorporeal veno-venous circuit from a support animal. This model provides stable and reliable function of the isolated lung for up to 3 h, thus overcoming some of the disadvantages of previous models. It may prove a potentially useful model for assessing ischaemic lung injury.

Comparison of propafenone to atenolol for the prophylaxis of postcardiotomy supraventricular tachyarrhythmias: a prospective trial.

To compare the efficacy of propafenone to atenolol in the prevention of supraventricular tachyarrhythmias (SVT) following cardiac surgery, 207 consecutive patients were randomly allocated to receive either propafenone 300 mg twice daily (105 patients) or atenolol 50 mg once daily (102 patients) orally for 7 days after operation. Double blinding was achieved using placebos. The end point was the development of a SVT which was symptomatic, recurrent, or lasting over 2 minutes, or the occurrence of adverse effects possibly attributable to the drugs. The groups were well matched for age, sex, bypass- and cross-clamp times, and other data. Thirteen patients in the propafenone group and 11 in the atenolol group developed SVT during the first week after operation. (P = 0.89, non significant, chi-squared with Yates' correction). In our study propafenone and atenolol were of approximately equal efficacy in preventing post cardiotomy SVT. Propafenone may have an advantage in being less negatively inotropic than atenolol; it could therefore be used in patients with poor left ventricular function or marginal haemodynamics when a beta blocker is contraindicated.

University of Wisconsin solution for lung graft preservation: which components are important?

Rat lung grafts were perfused with either Euro-Collins solution, University of Wisconsin solution, or one of six modified University of Wisconsin solutions that had been sequentially depleted of specific components (n = 5 each group). After storage at 4 degrees C for 6 hours, the isolated, ventilated pulmonary graft was reperfused for 1 hour with recirculating venous blood from a support animal. In a further group, lungs were reperfused immediately after explanation to provide control values. Grafts flushed with University of Wisconsin solution functioned at control levels with regard to oxygen tension: University of Wisconsin solution 128 +/- 2.7 mm Hg, control 126 +/- 5 mm Hg; graft blood flow: University of Wisconsin solution 9.9 +/- 0.4 ml/min, control 10.2 +/- 0.8 ml/min; peak airway pressure: University of Wisconsin solution 17 +/- 0.5 mm Hg, control 16.5 +/- 0.6 mm Hg; and weight gain: University of Wisconsin solution 0.12 +2- 0.1 gm, control 0.19 +/- 0.13 gm. In contrast, lungs treated with Euro-Collins solution functioned less well: oxygen tension 54 +/- 6 mm Hg, graft blood flow 3.5 +/- 0.42 ml/min, peak airway pressure 35 +/- 4 mm Hg, and weight gain 4.15 +/- 0.5 gm (p < 0.0001 all parameters). Sequential removal of hydroxyethyl starch, magnesium, allopurinol, adenosine, glutathione, and lactobionate from University of Wisconsin solution did not impair the efficacy of the solution.(ABSTRACT TRUNCATED AT 250 WORDS)

Lung graft preservation. Comparison of phosphate-buffered sucrose, modified EuroCollins, and University of Wisconsin solutions.

Phosphate-buffered sucrose (PBS) has been shown to be highly effective for renal graft storage. It may, therefore, be useful for lung graft storage. Recent studies have suggested a possible role for University of Wisconsin (UW) solution in lung preservation. The object of this study was to evaluate these two solutions in comparison with EuroCollins (EC) solution for lung graft preservation in an isolated rat lung model. Lungs were stored for 6 hr at 4 degrees C after a single pulmonary artery flush with either PBS with prostacyclin (n = 10), EC with prostacyclin (n = 5), or UW (n = 5) solution. Reperfusion of the isolated lung was carried out for 1 hr using a venovenous extracorporeal circulation from a ventilated support rat. The support animals and isolated lungs were ventilated with room air. Control values were obtained from lungs reperfused immediately after harvesting (n = 5). At 1 hr, PBS provided a similar level of protection to EC: pO2, 45 +/- 10 mmHg and 54 +/- 6 mmHg; graft blood flow, 4.1 +/- 1.2 ml/min and 3.5 +/- 0.42 ml/min; peak airway pressure, 32 +/- 2.5 mmHg and 36 +/- 3.6 mmHg; weight gain, 4.1 +/- 0.6 g and 4.2 +/- 0.6 g, respectively (P = NS). However, the UW group provided superior function, which was similar to the control group: pO2, 128 +/- 2.7 mmHg and 126 +/- 5 mmHg; graft blood flow, 9.9 +/- 0.4 ml/min and 10.2 +/- 0.8 ml/min; peak airway pressure, 17.6 +/- 0.4 mmHg and 16.5 +/- 0.6 mmHg; weight gain, 0.12 +/- 0.1 g and 0.19 +/- 0.13 g, respectively (P = NS). UW was superior in all parameters to PBS and EC (P < 0.001). This suggests that the renal solutions PBS and EC are inappropriate for lung graft preservation, and that the requirements of the lung during hypothermic storage differ from those of the kidney.

Prevention of a phrenic nerve palsy following left anterior mediastinotomy.

A left phrenic nerve palsy was observed following left anterior mediastinotomy performed for staging of a left upper lobe tumour. Since no evidence of mediastinal spread of the tumour was found, a left upper lobectomy was subsequently performed. Oedema (but no evidence of tumour) was seen around the phrenic nerve in the region of the previous mediastinotomy. As a result of this experience we have altered our technique of left anterior mediastinotomy.

Early and late results following combined coronary bypass surgery and mitral valve replacement.

To study the effect of various perioperative and operative variables, we analysed the results of 66 consecutive patients undergoing mitral valve replacement (MVR) and coronary artery bypass grafting (CABG). The mean age was 61.2 years (34 males and 32 females), the mean follow-up 54.71 +/- 7.8 months. The hospital mortality rate was 7.6% (5/66). New York Heart Association (NYHA) functional class (P < 0.01), left ventricular global wall motion score (increased scores indicating impaired function, P = 0.005) and cross-clamp time (P < 0.05) were associated with hospital mortality. There was no significant relationship of age (certainly up to the age of 70), cause of mitral valve disease, severity of mitral regurgitation, number of grafts, presence of angina, or previous myocardial infarction with hospital mortality. There were eight late deaths, survival at 1, 3 and 5 years was 92.4%, 83.2% and 80.2%, respectively. Although there was a trend for pulmonary vascular resistance (P = 0.15), NYHA class (P = 0.18) and aortic cross-clamp time (P = 0.09) to be associated with late survival, the only factor significantly related to late survival was global wall motion score (P = 0.001), i.e. those with scores of more than 10. Severity of mitral regurgitation and cause of mitral valve disease have been reported as being related to late survival in patients undergoing combined CABG and MVR, but we have found no such relationship. Our results indicate that both hospital and late mortality after this operation are strongly correlated with left ventricular function.