Postoperative speech impairment and cranial nerve deficits after secondary surgery of posterior fossa tumours in childhood: a prospective European multicentre study.

PURPOSE: Brain tumours constitute 25% of childhood neoplasms, and half of them are in the posterior fossa. Surgery is a fundamental component of therapy, because gross total resection is associated with a higher progression-free survival. Patients with residual tumour, progression of residual tumour or disease recurrence commonly require secondary surgery. We prospectively investigated the risk of postoperative speech impairment (POSI) and cranial nerve dysfunction (CND) following primary and secondary resection for posterior cranial fossa tumours. METHODS: In the Nordic-European study of the cerebellar mutism syndrome, we prospectively included children undergoing posterior fossa tumour resection or open biopsy in one of the 26 participating European centres. Neurological status was assessed preoperatively, and surgical details were noted post-operatively. Patients were followed up 2 weeks, 2 months and 1 year postoperatively. Here, we analyse the risk of postoperative speech impairment (POSI), defined as either mutism or reduced speech, and cranial nerve dysfunction (CND) following secondary, as compared to primary, surgery. RESULTS: We analysed 426 children undergoing primary and 78 undergoing secondary surgery between 2014 and 2020. The incidence of POSI was significantly lower after secondary (12%) compared with primary (28%, p = 0.0084) surgery. In a multivariate analysis adjusting for tumour histology, the odds ratio for developing POSI after secondary surgery was 0.23, compared with primary surgery (95% confidence interval: 0.08-0.65, p = 0.006). The frequency of postoperative CND did not differ significantly after primary vs. secondary surgery (p = 0.21). CONCLUSION: Children have a lower risk of POSI after secondary than after primary surgery for posterior fossa tumours but remain at significant risk of both POSI and CND. The present findings should be taken in account when weighing risks and benefits of secondary surgery for posterior fossa tumours.

The role of ICP overnight monitoring (ONM) in children with suspected craniostenosis.

PURPOSE: Secondary craniostenosis is a relevant problem pediatric neurosurgeons are confronted with and poses challenges regarding reliable diagnosis of raised ICP, especially in case of absent or questionable papilledema. How to identify children with elevated ICP is still controversial and diagnostics vary. We report on our experience with computerized ICP ONM in relation to imaging derived parameters. METHODS: Thirty-four children with primary or secondary craniostenosis and clinical suspicion of raised ICP were investigated. We compared clinical signs, history, and radiographic assessment with the results of computerized ICP ONM. Differences were significant at a p < 0.05. RESULTS: Baseline ICP was significantly higher in patients with combined suture synostosis, who also had a higher rate of questionable papilledema. Children with narrowed external CSF spaces in MRI had significantly higher ICP levels during REM sleep. Mean RAP was significantly elevated in patients with multi-suture synostosis, indicating poor intracranial compensatory reserve. Syndromal craniostenosis was associated with elevated ICP, RAP was significantly lower, and skull X-rays showed more impressions (copper beaten skull). RAP increased with more severe impressions only to decline in most severe abnormalities, indicating exhaustion of cerebrovascular reserve at an upper ICP breakpoint of 23.9 mmHg. Headaches correlated to lower ICP and were not associated with more severe X-ray abnormalities. CONCLUSION: Narrowed external CSF spaces in MRI seem to be associated to elevated ICP. Skull X-rays can help to identify patients at risk for chronically elevated ICP. Severe X-ray changes correlate with exhausted cerebrovascular reserve as indicated by RAP decline. Only ICP monitoring clearly identifies raised ICP and low brain compliance. Thus, in cases with ambiguous imaging, ONM constitutes an effective tool to acquire objective data for identification of surgical candidates.

The effect of ion composition on cellular membrane potentials during selective coronary arteriography.

An animal experimental study on seven thoracotomized dogs was designed to investigate the effects of intracoronarily injected sodium meglumine diatrizoate on myocardial electrophysiology and to evaluate the contribution of the corresponding changes of electrolyte levels in coronary blood. For this purpose the effects of alterations in the Na+-, K+- and Ca++-concentrations in coronary blood were studied separately by intracoronarily injected model solutions. Membrane potentials were recorded from the left ventricular myocardium by a modified microelectrode technique which is applicable to the beating and blood perfused heart in situ. Following selective coronary arteriography there was a temporary hyperpolarization of resting potentials and a prolongation of action potentials which may be explained by a contrast-induced local deficiency of potassium and calcium ions and by a relative prevalence of sodium ions in coronary blood. In selective coronary arteriography the synchronicity of cardiac excitation is disturbed by the regional prolongation of action potentials, which may induce ventricular arrhythmias.

DPTI/STTI--an index of the myocardial oxygen supply/demand ratio?

The DPTI/STTI (diastolic pressure-time index/tension-time index) ratio is applied as an indicator of myocardial ischemia particularly in cardiovascular and anesthesiologic care units. The validity of the DPTI/STTI ratio was examined in intact dogs with large variations of oxygen supply and demand. The correlation of DPTI/STTI to the directly measured oxygen supply/demand ratio was poor even under maximal coronary vasodilation. Many data points were far below the critical DPTI/STTI values (reported previously) without occurrence of myocardial ischemia, failure, or edema. Therefore caution is necessary if the DPTI/STTI ratio is to applied to humans.

Decrease in cardiotoxicity of contrast media in coronary angiography by addition of calcium ions: a combined experimental and clinical study.

The cardiotoxicity of commonly used contrast media such as sodium methylglucamine diatrizoate is related to nonphysiologic concentrations of ions and high osmolality. Following injection there is an excessive decrease in ambient calcium which disturbs the extracellular Na+/Ca2+ ratio and results in myocardial depression. In animal studies (anesthetized, intact mongrel dogs) this cardiodepressive effect could be fully compensated by adding 22.5 mEq/1 of ionic calcium to the contrast medium. In 16 patients studied for coronary artery disease (CAD) 72 injections of sodium methylglucamine diatrizoate, mainly in the left coronary artery, were thoroughly investigated. There was marked depression of left ventricular pressure (-22%) and (dP/dt)max (-27%), and marked heart rate slowing (-29%). Added calcium in the concentration cited reduced significantly (p < 0.001) the myocardial depression to -15% and -13%, respectively, but did not completely compensate it. The heart rate slowing was not altered significantly. It was concluded that the addition of calcium may be helpful when studying high-risk patients and using high injection volumes.

238U/235U variations in meteorites: extant 247Cm and implications for Pb-Pb dating.

The 238U/235U isotope ratio has long been considered invariant in meteoritic materials (equal to 137.88). This assumption is a cornerstone of the high-precision lead-lead dates that define the absolute age of the solar system. Calcium-aluminum-rich inclusions (CAIs) of the Allende meteorite display variable 238U/235U ratios, ranging between 137.409 +/- 0.039 and 137.885 +/- 0.009. This range implies substantial uncertainties in the ages that were previously determined by lead-lead dating of CAIs, which may be overestimated by several million years. The correlation of uranium isotope ratios with proxies for curium/uranium (that is, thorium/uranium and neodymium/uranium) provides strong evidence that the observed variations of 238U/235U in CAIs were produced by the decay of extant curium-247 to uranium-235 in the early solar system, with an initial 247Cm/235U ratio of approximately 1.1 x 10(-4) to 2.4 x 10(-4).

[Aortic valve structures as landmarks for determining coronary artery ostia in transthoracic echocardiography]. / Aortenklappenstrukturen als Orientierungshilfe zum Auffinden der Koronararterienabgänge in der transthorakalen Echokardiographie.

BACKGROUND: Occasionally, coronary arteries are recorded in transthoracal echocardiography. The question was if this modality could be used as non-invasive screening method of the coronaries. A prerequisite for this is an exact and reproducible measurement of the origin of the coronary arteries. MATERIAL AND METHOD: The topography of the coronary ostia in relation to the aortic valve was examined morphometrically in the aortae of 20 embalmed cadavers and 50 patients of a cardiologist's practice who underwent transthoracal echocardiography. RESULTS: In all cases, the coronary arterial orifices were located eccentrically in the coronary sinus, shifted to the non-coronary aortic sinus. The distance between left coronary orifice to the commissure of the left and the right semilunar valvula was 13.3 mm on average in the anatomical measurements, whereas in the echocardiography this distance was 14.3 mm. The distance between the left ostium and the attachment of the left and the posterior semilunar valvula 9.4 mm, corresponding to 11.6 mm in echocardiography. The distance between right coronary orifice and the attachment of the right and the left semilunar valvula was 18.0 and 17.3 mm respectively, and the distance between right coronary orifice and the commissure of the right and the posterior semilunar valvula accounted for 8.5 and 9.7 mm respectively. On the average, the ostia were located 3.9 mm below the level of the sinotubular junction. Multiple ostia occurred in 65%, 92% of these were in the right coronary aortic sinus, shifted from the main orifice to the attachment of the right and the left semilunar valvula. CONCLUSION: In the cardiologist's routine, the attachments of the aortic leaflets proved to be very useful as landmarks. The coronary arterial orifices have been educible in nearly all cases. These results show that transthoracal echocardiography may be used in the screening for coronary artery disease.

Comparison of the effects of right atrial, right ventricular apex and atrioventricular sequential pacing on myocardial oxygen consumption and cardiac efficiency: a laboratory investigation.

As the impact of cardiac pacing on myocardial energetics has not yet been established, this laboratory investigation was undertaken to evaluate the effects of right atrial (AP), right ventricular apex (VP) and atrioventricular sequential pacing (AVP) on cardiac energetics in a closed-chest model. Ninety-two pacing interventions were performed in ten anesthetized mongrel dogs with normal loading conditions and contractile states. The energetic effects of pacing were assessed in terms of myocardial oxygen consumption (MVO2), its hemodynamic determinants and cardiac efficiency. Efficiency was calculated as the ratio of O2-equivalent of external cardiac work to MVO2, using standard definitions. In the first series of experiments 36 intra-individual comparisons were made between AP and VP at identical rates (95-210 beats/min). In the second series AVP was compared to VP in 10 intra-individual comparisons at identical rates (109-190 beats/min). MVO2 was lower (p less than 0.001) during AP (8.30 +/- 2.14 ml O2/min.100 g) compared to VP (10.16 +/- 3.15 ml O2/min.100 g) at the same rate (158 +/- 32 beats/min). Efficiency (p less than 0.001) was considerably higher during AP (21.6 +/- 5.7%) compared to VP (12.8 +/- 5.9%). During AVP, MVO2 (10.85 +/- 1.76 ml O2/min.100 g) was not significantly different from VP (10.57 +/- 1.34 ml O2/min.100 g) at the same rate (146 +/- 25 beats/min). Hemodynamics were superior with AVP compared to VP. Efficiency was significantly higher (p less than 0.01) with sequential (15.4 +/- 3.9%) as compared to ventricular pacing (12.0 +/- 3.2%). In conclusion, this study indicated that VP exerts disadvantageous effects on MVO2 and cardiac efficiency. AP has beneficial effects on cardiac energetics because it improves the relationship between mechanical performance of the heart and its energy requirements. AVP results in a higher efficiency than VP due to superior hemodynamics, despite MVO2 levels comparable to those of VP. The mechanism of energy waste with right ventricular apex pacing is probably related to an asynchronous contraction in the ventricular myocardium due to a nonphysiological spread of excitation.

Basic physiological studies on cardiac pacing with special reference to the optimal mode and rate after cardiac surgery.

Temporary cardiac pacing (CP) is frequently applied postoperatively in the management of low cardiac output (CO) and rhythm instability. However, uncertainty exists about the "optimal" pacing rate, range and mode due to incomplete information on myocardial oxygen consumption (MVO2), related to its hemodynamic determinants, and on myocardial pumping efficiency (eta) at CP. In 10 intact dogs atrial pacing (AP) (90 to 210 beats/min) and ventricular pacing (VP) (70 to 330 beats/min) were investigated in normal and failing hearts. AP and VP were compared at identical rates. MVO2 (4 to 20 ml/min . 100 gr) was measured directly according to the Fick principle. Cardiac efficiency was calculated as the ratio of oxygen equivalent of external cardiac work to MVO2. Rates with maximum CO and a maximal eta occurred only in heart failure. However, maximal CO and eta were obtained at different heart rates (HR). MVO2 was significantly higher (p less than 0.001) under VP as compared to AP at identical rates with a mean increase of 26.5% +/- 6% over AP, although hemodynamics were significantly lower under VP (p less than 0.001). Myocardial pumping efficiency was markedly better under AP with a mean increase of 63% +/- 4.5% over VP even in normal heart. Adjustment of HR at maximal response in CO may become dangerous, particularly under VP, in heart failure. AP, if applicable, may be regarded as the optimal pacing technique due to an optimal relation of improved hemodynamics to MVO2. It may be helpful in correcting an imbalance between oxygen supply and demand in cases of low output syndrome. The pathophysiologic mechanisms and further clinical implications are discussed.

Influence of arteriographic contrast media on the Na+/Ca++-ratio in blood.

To investigate the basis of cardiodepressive side effects in coronary arteriography, the isolated effects of different contrast media on electrolyte levels in blood (and blood fractions) were quantified in vitro. Due to their sodium content and calcium chelation, ionic media cause an imbalance in the extracellar Na+/Ca++-ratio that determines myocardial contractility. Ca++-chelation exceeded that due to stabilizing additives indicating a binding by the contrast agents themselves. The amount of calcium bound varied with different media and was greatest with Renografin. It is suggested that the degree of Na+/Ca++-imbalance in blood explains the extent of acute cardiodepression.

Unfavorable effects of ventricular pacing on myocardial energetics.

The effects of ventricular pacing (90-330 beats/min) and atrial pacing (120-210 beats/min) on myocardial oxygen consumption (MVO2) and its hemodynamic determinants and on myocardial pumping efficiency were studied systematically on intact dogs. In six closed-chest experiments 158 steady states were analyzed. Myocardial blood flow was measured with a differential pressure sinus catheter, oxygen consumption (5-30 ml/min . 100g) was determined simultaneously by the Fick principle and the additive hemodynamic parameter Et. Ventricular and atrial pacing were compared with both methods at identical heart rates. Additionally, the coincidence between both methods of determining MVO2 was examined at sinus rhythm with sympathetic stimulation (norepinephrine, atropine) within each experiment. Ventricular pacing increased MVO2 overproportionally up to 50% in relation to the hemodynamic determinants. Consequently, myocardial pumping efficiency markedly decreased with increasing ventricular rate. The close relation between directly measured MVO2 and Et, found in previous studies, was maintained under sympathetic stimulation. Atrial pacing, as compared to ventricular pacing at identical rates, resulted in a decrease of MVO2 up to 25% although the expected mVO2 according to its hemodynamic determinants rather increased. The hemodynamic and metabolic mechanisms probably responsible for the energetic difference between ventricular and atrial pacing at equal heart rates are discussed.

[Reduction in cardiotoxicity of ionic contrast media used in coronary angiography by added calcium--Clinical study (author's transl)]. / Die Reduktion der kardialen Nebenwirkungen ionischer Kontrastmittel bei der Koronarangiograhie durch Kalziumzusatz. Klinische Studie.

In 16 patients with CAD, hemodynamic and electrophysiologic side effects were examined following selective coronary artery injections with Urografin 76%, a commonly used ionic contrast medium. A Millar transducer tipped catheter was placed in the left ventricle for continuous pressure recording also during injections. The unmodified contrast medium decreases peak left ventricular pressure (-22 +/- 8%) and dp/dt max (-27 +/- 13%) markedly at injection. With added calcium (22.5 mEq/l) this cardiodepressive reaction becomes diminished to -15 +/- 7% and -13 +/- 8% respectively with high significance (p < 0.001). This positive effect is even more marked using higher volumes of contrast material for injection. In contrast to animal experiments, calcium did not completely compensate the negative inotropic reaction even in higher concentration (33.75 mEq/l). The marked sinus slowing (-29 +/- 14%)--observed in patients and not influenced by the calcium addition--has an additional effect in the sense of a "negative frequency-inotropism" and is responsible for the residual cardiodepressive reaction. An influence on electrophysiologic side reactions can also be observed with added calcium but only in injections with higher volumes of contrast medium. QT-elongation, T-wave changes are reduced significantly. We did not see any unfavorable reactions caused by added calcium. The cardiodepressive side effects on the contractile force by commonly used ionic contrast media can be reduced by adding calcium in the above-mentioned concentration. This may be helpful when studying high risk patients and using high injection volumes.

[Coronary angiography in chronic and acute coronary artery disease. Advantages of a low osmolality contrast medium]. / Koronarangiographie im chronischen und akuten Stadium der koronaren Herzkrankheit. Vorteile eines niederosmolaren Kontrastmittels.

The advantages of a new low osmolality contrast medium (sodium meglumine ioxaglate) in clinical coronary angiography are demonstrated at two groups of patients in comparison to sodium meglumine diatrizoate. One group included patients undergoing diagnostic angiography in chronic state of CHD, the other during diagnosis and therapy (intracoronary lysis) in state of acute myocardial infarction. Injection of the low osmolality contrast material was followed in both groups by significant reduction of pressure drop and cardiac slowing. In both groups there was also a reduction of changes in ECG compared to side effects of the conventional contrast material.

Effects of AR-L 115 BS on hemodynamics, myocardial oxygen consumption and cardiac pumping efficiency.

The effects of 2-[(2-methoxy-4-methylsulfinyl)phenyl]-1H-imidazo[4,5-b]pyridine (AR-L 115 BS) on hemodynamics, myocardial oxygen consumption and cardiac pumping efficiency were tested on closed-chest dogs in cardiac catheterization technique. Doses in the range of 0.1 up to 4.0 mg/kg b. w. were injected i.v. A therapeutical dose is to be expected in the range of 1.0 mg/kg b. w., showing a distinct positive inotropic effect and reducing endsystolic volume without increase of heart rate and myocardial oxygen consumption.

[Reduced cardiotoxicity of contrast media in angiocardiography. Comparative clinical study using diatrizoate with added calcium or metrizamide (author's transl)]. / Reduktion kardialer Nebenwirkungen von Röntgenkontrastmitteln in der Angiokardiographie durch Zusatz von Kalzium und Verwendung eines nichtionischen Kontrastmittels.

Cardiodepressive side effects of angiocardiography can be reduced by using non-ionic metrizamide (Amipaque) or adding calcium to diatrizoate (Urografin 76%). In 15 patients with coronary artery disease undergoing heart catheterization, we compared cardiac side effects of coronary angiography and left ventricular angiography using metrizamide and diatrizoate with and without additional calcium (11.3 mmol/l) as contrast media under randomized conditions. In selective intracoronary injection with diatrizoate alone, peak left ventricular pressure and contractility (dP/dtmax) showed a fall of 30 +/- 11% and 31 +/- 15% (n = 33 injections). Using diatrizoate with added calcium (11.3 mmol/l), the fall was only 23 +/- 12% and 20 +/- 10% respectively (n = 31 injections). With metrizamide (n = 32 injections) cardiac side effects are even less and the decrease in pressure and contractility only 13 +/- 10% and 7 +/- 7% respectively, which its highly significant (p less than 0.0001) compared with the effect of diatrizoate. The heartrate slowing, not essentially altered by calcium addition, was minimal using non-ionic metrizamide. In left ventricular angiography, the pressure fall in the late phase after injection of diatrizoate, caused by decrease peripheral vascular resistance (vasodilation), was lacking when injecting metrizamide (p less than 0.001). Metrizamide has even less cardiodepressive side effects than diatrizoate with additional calcium when used in angiocardiography and seems to be suitable particularly for the evaluation of high risk patients.

Experimental validation of methods for the measurement of coronary sinus blood flow in man.

The measurement accuracy of clinically applicable methods for blood flow measurement in coronary sinus -- continuous local thermodilution (LTD), differential pressure (DP), ultrasonic Doppler (US) and the electromagnetic flow measurement method (EMF) -- was examined in 15 anaesthetized closed chest dogs with left ventricle weights between 150 and 200 g. The LTD, DP, US and the EMF were examined in each experiment in the two following arrangements. 1. In coronary sinus -- left jugular vein by-pass: This arrangement allowed four reference methods for measurement of coronary sinus blood flow (CBF). 2. In "clinical" position, without by-pass, which allowed two reference methods for CBF measurements. The results on the measurement accuracy of the LTD, DP and US are, depending on the measurement arrangement, contradictory. In the by-pass arrangement 1 there was observed a good agreement of the LTD, DP and US CBF values with the reference values. In the "clinical" position, without by-pass 2 the measurement accuracy of LTD was not sufficient for exact measurement of CBF and derived parameters. The examined velocity tip flow probes (US, DP) gave no correlation with the reference methods. US and DP are even for semiquantitative estimation of CBF unsuitable. The EMF tip flow probe was for the CBF measurement unsuitable, because of disturbance by the electrical activity of myocardium.

Supernova Sources and the 92Nb-92Zr p-Process Chronometer.

We report new Zr isotope evidence for live (92)Nb (mean life: tau&d1;92Nb=52 Myr) within the early solar system resulting in &parl0;92Nb&solm0;93Nb&parr0;initial approximately 10-3. The meteoritic minerals rutile and zircon have, respectively, very high and very low Nb/Zr ratios and are ideal for exploring the (92)Nb-(92)Zr chronometer. Rutiles exhibit high positive straightepsilon92Zr ( approximately 14-36) while a zircon has a negative straightepsilon92Zr ( approximately -4), as would be expected if (92)Nb was live in the early solar system. The meteoritic rutiles appear to be young, with apparent times of formation of approximately 80-220 Myr subsequent to the origin of the solar system. The initial (92)Nb/(92)Mo for the solar system is broadly compatible with a model of uniform production if the (92)Nb/(92)Mo production ratio for Type II supernova (SNII) sources with neutrino-driven winds is used. Data for all the now extinct p-process nuclides ((92)Nb, (97)Tc, and (146)Sm) are consistent with these isotopes being derived by uniform production from SNII sources and a free decay interval of approximately 10 Myr. Consideration of a range of models indicates that the average p-process production ratio of (92)Nb/(92)Mo needs to be at least in the range of 0.06-0.25.