Effect of intracerebral norepinephrine depletion on outcome from severe forebrain ischemia in the rat

Manipulations of plasma catecholamine concentrations influence outcome from ischemic brain insults. It has been suggested that these effects are mediated by influences on brain catecholamine concentrations. This study examined whether major changes in brain norepinephrine concentrations can alter outcome from severe forebrain ischemia. Sprague-Dawley rats were administered 50 mg/kg i. p. N-(chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4) or were left untreated (control). One week later, these rats were subjected to either 7 or 8 min of normothermic forebrain ischemia (bilateral carotid occlusion and MABP=30 mmHg) and allowed to recover for 4 days. Histologic damage was then evaluated. In other control and DSP-4-treated animals, hippocampal microdialysate norepinephrine concentrations were measured before, during and after 8 min of forebrain ischemia. Norepinephrine concentrations were also determined in brain homogenates from non-ischemic DSP-treated and control rats. A 95% depletion of norepinephrine was observed in brain homogenates from non-ischemic DSP-4-treated rats compared with control. During ischemia, microdialysate norepinephrine concentrations increased in control but not in DSP-4-treated rats (P=0.002). For plasma, intra-ischemic epinephrine concentrations increased 8-10-fold and returned to baseline values post-ischemia with no differences between groups. Plasma norepinephrine values remained unchanged in both groups. Histologic damage resulting from either 7 or 8 min of ischemia in hippocampal structures, caudoputamen, and neocortex was similar between DSP-4-treated and control groups. This study could not identify any effect of major changes in brain norepinephrine concentrations on ischemic brain damage. These data indicate that peripheral catecholamine effects on near-complete forebrain ischemic outcome are unlikely to be mediated by effects on central catecholamine concentrations.     

The World Bank's perspective on global health

Over the next 25 years, as populations age and tobacco consumption increases, most developing regions will likely see noncommunicable diseases become the leading causes of disability and premature mortality. The already existing problems of malnutrition and infectious diseases will remain. In this context, the World Bank is examining its role and contribution to global health. From a small start approximately 25 years ago, the Bank has greatly expanded its role in international health, population, and nutrition to become the largest single external financier of health activities in low- and middle-income countries. Many other Bank-supported activities affect health, including poverty reduction, housing, water and sanitation, and the education of girls. The Bank is also increasingly active in health policy debates, publishing numerous studies annually. Most of these studies focus upon specific countries, but some address key issues of concern to many developing countries. This article explains why the Bank continues to expand its resources devoted to health and the rationale for the changing emphasis of its activities in the field.     

Spiro-ergometric studies after corrective surgery of tetralogy of Fallot]

Treadmill exercise electrocardiography and spirometry was recorded in 61 patients (aged from 5 to 23 years) who underwent corrective surgery for tetralogy of Fallot. The Bruce-protocol and a modified interval-protocol were compared to find out their ability to induce arrhythmias. Supraventricular arrhythmias were predominantly provoked by the interval-protocol while maximal exhaustion is often necessary for inducing ventricular arrhythmias which we found in 23% of our patients. Most of them were seen in the periods of recovery between or after the exercise. We propose a combination of both protocols, which will be compared with established forms of exercise-testing in further studies. The results of rhythm analysis of consecutive exercise tests in one patient after surgical repair could possibly be compared by using an "arrhythmia score" which tries to indicate the severity of different forms of arrhythmias. The values of maximal heart rate, oxygen consumption and endurance time recorded at maximal exercise (Bruce-protocol) were about 15% lower than correspondent values of healthy persons found by other authors.     

Risk of intracranial aneurysm surgery in the good grade patient: early versus late operation

To evaluate the risk of definitive intracranial microsurgical aneurysm obliteration as a function of the timing of the operative intervention, we retrospectively reviewed 106 consecutive patients in good clinical condition who underwent such surgery. The patients who were operated upon within the first 8 days of their most recent subarachnoid hemorrhage formed the "early" group; the patients operated upon between the 9th and 31st day were considered to have undergone "late" surgery. On the basis of their clinical outcome the patients were allocated to one of four outcome categories ("good," "fair," "death") both at the time of their hospital discharge and at their most recent clinical re-evaluation, a minimum of 6 months after discharge from the hospital. There was no significant difference in the operative mortality in each group (early surgery, 5%; late surgery, 4%); additionally, no significant difference was noted in the incidence of either intraoperative complications or postoperative morbidity. A suggestive but statistically insignificant increase in the incidence of postoperative cerebral ischemic events was seen in the "early" surgery group (8% vs. 4% for the "late" surgery group). The potential significance of these findings for the timing of intracranial aneurysm surgery is discussed.     

B‐Cell lymphoproliferative disorder not associated with Epstein‐Barr Virus in a child with relapsed acute lymphoblastic leukemia

Lymphoproliferative disorder (LPD) is described in only a few children receiving chemotherapy for cancer. In all of them, an association between LPD and EBV (Epstein‐Barr Virus) was found. We report on a patient who developed LPD not associated with EBV while receiving chemotherapy for relapsed acute lymphoblastic leukemia (ALL). Despite discontinuation of chemotherapy, administration of intravenous immunoglobulins and surgery the patient died. Growing experience with this disorder may allow better treatment options in the future and will show whether LPD not associated with EBV requires different therapeutic strategies. Med Pediatr Oncol 2003;40:13–17, © 2003 Wiley‐Liss, Inc.     

A comparison of strain-related susceptibility in two murine recovery models of global cerebral ischemia

Genetically engineered mice are increasingly important in stroke research. The strains on which these constructs are built are known to have inherent differential sensitivities to ischemic insults. This has been largely attributed to differences in vascular anatomy. This study compared the outcome from forebrain ischemia in two common murine background strains using two different types of ischemic insult. C57Bl/6 and SV129 mice were subjected to two vessel (bilateral carotid) occlusion (2VO) or 2VO plus systemic hypotension (2VO+Hypo; mean arterial pressure=30+/-2 mmHg) for 10-20 min. Ventilation and pericranial temperature were controlled. Cerebral blood flow (CBF) was determined by 14C-iodoantipyrine autoradiography. Histologic damage in forebrain structures was measured 3 days post-ischemia. During 2VO+Hypo, the EEG became isoelectric in all animals. During 2VO alone, EEG isoelectricity occurred in 73% of C57Bl/6 and 50% of SV129 mice. Forebrain CBF was reduced to a similar extent in both strains. Greater CBF variability was seen with 2VO alone versus 2VO+Hypo. CBF was less in the 2VO+Hypo model. SV129 mice had wider posterior communicating but smaller basilar artery diameters. With or without hypotension, SV129 mice had markedly less severe histologic damage than C57Bl/6 mice. A time-dependent increase in histologic damage was demonstrated in the 2VO+Hypo model but not with 2VO alone. The 2VO and 2VO+Hypo models produced similar magnitudes of histologic injury in C57Bl/6 mice subjected to 10-min ischemia. SV129 mice were resistant to ischemia in either model. The 2VO+Hypo model produced a more uniform severity of ischemia as defined by CBF and EEG examination. Despite this, the murine strain had a substantially greater impact on histologic outcome than did cerebrovascular anatomy or the type of model used to produce the ischemic insult.     

Uredinorubellins and caeruleoramularin, photodynamically active anthraquinone derivatives produced by two species of the genus ramularia

Both the phytopathogenic fungus Ramularia collo-cygni and the hyperparasite R. uredinicola biosynthesize a number of red and yellow anthraquinone derivatives called rubellins. The new compounds uredinorubellins I and II, which were isolated from R. uredinicola, contribute to understanding the biosynthesis pathway that leads from simple anthraquinones to the rubellins. In addition, we isolated for the first time such simple compounds as chrysophanol and helminthsporin from both Ramularia species. A blue compound isolated from the mycelium of R. collo-cygni was revealed to be a unique 9,4-anthracenedione derivative. Structure elucidation by (1)H and (13)C NMR of the new but unstable compound caeruleoramularin was possible only by feeding the fungus different labeled (13)C acetates. The photodynamic activity of the uredinorubellins was comparable to rubellin D, whereas chrysophanol and caeruleoramularin did not display such activity.     

Nasal continuous positive airway pressure (n-CPAP) does not change cardiac output in preterm infants

Our objective was to study how invasive mechanical ventilation impairs cardiac output (CO) in children and adults. Although the application of continuous positive airway pressure (CPAP) is widely practiced in neonatal intensive care, its hemodynamic consequences have not yet been investigated. A prospective study to assess the hemodynamic effects was conducted in 21 preterm infants < 1500 g using two-dimensional M-mode and pulsed Doppler echocardiography during and 1 hour after discontinuation of nasal CPAP (n-CPAP). Gestational age was 28.0 +/- 1.9 weeks (mean +/- standard deviation); birthweight, 1000 +/- 238 g; age at study entry, 200 +/- 155 hours; total maintenance fluid, 154 +/- 42 mL/kg/day; and n-CPAP level, 4.4 +/- 0.9 cm H(2)O. None of the infants received inotropic support, and n-CPAP did not cause any significant difference in the parameters measured: stroke volume, 3.1 +/- 1.0 mL (with n-CPAP) versus 3.1 +/- 1.0 mL (without n-CPAP); cardiac output, 487 +/- 156 mL/minute versus 500 +/- 176 mL/minute; left ventricular diastolic diameter, 1.22 +/- 0.15 cm versus 1.24 +/- 0.14 cm; fractional shortening, 0.30 +/- 0.05% versus 0.29 +/- 0.04%; and aortic velocity-time integral, 8.64 +/- 1.80 cm versus 8.70 +/- 1.65 cm. The n-CPAP level did not influence CO; n-CPAP (up to 7 cm H (2)O) has no echocardiographically detectable hemodynamic effect in preterm infants. Our data imply there is no need to withhold n-CPAP support to prevent circulatory compromise in these infants.