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PubMed2004

The technique of ophthalmic arterial infusion therapy for patients with intraocular retinoblastoma.

Recently, there has been increasing interest in treating intraocular retinoblastoma with systemic chemotherapy combined with focal laser therapy and cryotherapy instead of radiotherapy. We developed a system of selective ophthalmic arterial infusion (SOAI) therapy, administering melphalan, the agent which had the greatest effect on retinoblastoma in a clonogenic assay. The SOAI system consists of a combination of a micro-balloon, a guiding catheter, and a flushing hub. After selective catheterization to the cervical segment of the internal carotid artery by the guiding catheter, the micro-balloon was propelled to the portion just distal to the orifice of the ophthalmic artery. During temporary occlusion of the internal carotid artery, melphalan was infused from the introduced catheter tip. We treated 187 patients with intraocular retinoblastoma with SOAI; 563 SOAIs were performed for 610 eyes. The technical success rate was 97.51%. Fourteen examinations failed. No significant complication due to catheterization (including brain infarction) was detected. SOAI, using the balloon occlusion technique, is safe, and its use will prevent the side effects that occur with systemic chemotherapy, and eliminate the need for irradiation and enucleation.

Antineoplastic Agents, Alkylating↗
PubMed2006

Aortic arch atheroma and the risk of stroke.

Brain infarction of unknown cause, known as cryptogenic stroke, represents 30% to 40% of all ischemic strokes, or approximately 400,000 cases each year in western Europe. In this category of patients new potential causes, such as aortic arch atheroma in the elderly, have been investigated in the past two decades.

Aorta, Thoracic↗
PubMed1990

The "stuck twin" phenomenon: ultrasonographic findings, pregnancy outcome, and management with serial amniocenteses.

Thirteen consecutive twin pregnancies affected by the "stuck twin" phenomenon were reviewed to determine the potential benefit of serial amniocenteses. The fetal survival rate for the eight pregnancies that underwent serial amniocenteses was 69% (11 of 16 fetuses). This is significantly improved compared with a fetal survival rate of 20% among the five preceding pregnancies managed without serial amniocenteses at the same institution (p = 0.01). It is also markedly improved compared with a combined fetal survival rate of 16% among 48 previously reported pregnancies with the stuck twin phenomenon managed without serial amniocenteses (p less than 0.0001). Survival correlated with the absence of concomitant pregnancy complications (i.e., maternal hypertension or intractable labor) and with the absence of severe fetal structural abnormalities. Procedural complications occurred in three of eight pregnancies (37.5%) managed with serial amniocenteses and was attributed as a cause of fetal death in one case. Two of 11 survivors (18%) had complications after serial amniocenteses including brain infarction and renal tubular necrosis. Serial amniocenteses may significantly improve the survival rate of twin gestations affected by the stuck twin phenomenon but may be associated with complications among survivors.

Amniocentesis↗
PubMed1995

Do concepts of causes and prevention of cerebral palsy require revision?

OBJECTIVE: My purpose was to explore the criteria of The American College of Obstetricians and Gynecologists (Technical Bulletin No. 163) for perinatal asphyxia to be linked to subsequent cerebral palsy. STUDY DESIGN: Analysis of four cases of intrapartum fetal insults with subsequent cerebral palsy and a literature review are presented. RESULTS: All of the four cerebral palsy cases had sufficient intrapartum causes of cerebral palsy, yet none fulfilled The American College of Obstetricians and Gynecologists' linkage criteria. Complications in the cerebral palsy cases were as follows: maternal intrapartum cardiac arrest, fetal skull fracture with brain infarct, intrapartum fetal stroke, and a newborn delivered after uterine rupture with only central nervous system defects. There are no well-done laboratory or clinical studies that unequivocally support the "criteria" that umbilical artery pH must be < 7.00 or the requirements of Apgar score < 3, hypoxic-ischemic encephalopathy, and multiple organ dysfunction. Apparent exceptions to these criteria occur. CONCLUSIONS: The American College of Obstetricians and Gynecologists Technical Bulletin's criteria for cerebral palsy linkage and the role of parturition in cerebral palsy should be reevaluated. A rebirth of obstetric enthusiasm for cerebral palsy research, teaching, and treatment needs to occur.

Blood↗
PubMed1996

Alcohol and coronary heart disease: the evidence for a protective effect.

There is a considerable body of evidence indicating that moderate alcohol intake is associated with a reduced incidence of, and mortality from, coronary heart disease (CHD). There is also substantial evidence that problem drinking (well beyond two drinks per day) is associated with increased cardiovascular mortality. However, the frequently reported harmful effect of alcohol abuse on CHD mortality rates could be a result of mislabelling as CHD conditions such as alcohol-induced dilated cardiomyopathy, dysrhythmias, and hypertensive cardiovascular disease. The combination of protective and harmful influences of alcohol consumption results in a U-shaped mortality curve. A true protective effect of moderate intake of alcohol is likely, because of consistent findings in many large, well-conducted studies of diverse population samples and the apparent specificity of the protective effect for CHD and possibly atherosclerotic-thrombotic brain infarction. There are also biologically plausible mechanisms whereby the protection might be conferred. Alcohol has been shown convincingly to raise HDL subfractions which have been found to be protective against CHD, and it may also provide protection by an antithrombotic effect. There is a suggestion that wine, and red wine in particular, may be more protective than other alcoholic beverages. However, it is difficult to control adequately for confounding factors, since persons who prefer wine have been found to have a more advantageous lifestyle, a better cardiovascular risk profile, are better educated, and smoke less. The evidence for a protective effect of moderate alcohol intake includes population studies of alcohol and CHD mortality in 20 countries, case-control studies, prospective cohort studies, arteriographic studies, and animal experiments. Nevertheless, because there are no controlled trial data, it is possible that some other factor may be responsible for the apparent protective effect of alcohol. The inclusion of former drinkers or sick individuals in the non-drinker category, and lack of control for cigarette smoking and other risk factors, have been excluded as reasons for higher CHD rates among individuals who do not consume alcohol. No alternative explanation for the protective effect has surfaced after two decades of investigation of the alcohol-CHD relationship, yet, the penalties of heavy alcohol consumption are too large to ignore. Until we can be sure that advice that encourages the public to drink to avoid coronary heart disease does not increase abuse, we must be cautious in making general recommendations.

Alcohol Drinking↗
PubMed1994

Extracorporeal fibrinogen and platelet precipitation as a new haemorheological treatment for acute stroke.

In thromboembolic brain infarctions high fibrinogen levels are associated with an increase of both plasma and whole blood viscosity as well as increased aggregability of blood cells. This decreases cerebral perfusion and might reduce blood flow in the penumbra surrounding infarction. An important goal in the treatment of acute cerebral infarction is to reduce fibrinogen and thereby improve the haemorheological state. Heparin-induced extracorporeal low-density lipoprotein/fibrinogen precipitation (HELP) appears to be successful in achieving this. Such treatment reduces lipid fractions, including total cholesterol, low-density lipoproteins (LDL) and triglycerides (p < 0.0001 each), as well as fibrinogen (p < 0.0001) in a safe and efficacious manner. Whole blood and plasma viscosity are also improved when measured by oscillo-rheometry. Furthermore, the number and aggregation tendency of blood cells is influenced positively as determined by Coulter counting and aggregometry. HELP improves the haemorheological profile to a degree which has not been achieved by haemorheologically active substances.

Acute Disease↗
PubMed1991

Non-synaptic mechanisms of Ca(2+)-mediated injury in CNS white matter.

Clinical deficits after injury to the CNS are due, in large part, to dysfunction of white matter (myelinated fiber tracts), including descending and ascending tracts in the spinal cord. A crucial set of questions, in the search for strategies that will preserve or restore function after CNS injury, centers on the pathophysiology of, and mechanisms underlying recovery of conduction in, CNS white matter. These questions are relevant both to spinal cord injury, and to brain infarction, which frequently affects white matter.

Animals↗
PubMed1995

The black hole in Charley Toorop's "The three generations": a neuro-iconographic analysis and reconstruction.

The painting "The Three Generations" is considered one of the highlights in Charley Toorop's works. It essentially represents a self portrait of the artist herself, with John Rädeker's sculpture of her father Jan Toorop, and her son Edgar Fernhout. The completion of this painting took 9 years (1941-1950). However, the left lower corner of the canvas, sometimes referred to as "the black hole", Charley's left thumb with the palette and the conspicuously raised right arm with the brush can be considered structural imperfections. During the last 5 years of her life Charley Toorop suffered at least three cerebrovascular accidents, which raises the question whether the described pictorial inadequacies were of a neuropathological origin. Closer examination of the "black hole" area on the canvas disclosed a subtle ridge, as predicted and reconstructed by computer image manipulation. It is argued that Charley Toorop suffered multiple brain infarctions with subsequent partial visuo-spatial agnosia which prevented her from either recognizing and/or restoring the alleged imperfections in the painting "The Three Generations".

Agnosia↗
PubMedDate not supplied

Sequential computed tomography in tuberculous meningitis in infants and children.

Clinical and serial CT findings in 9 children, mainly infants with advanced tuberculous meningitis are presented. Hydrocephalus, tuberculomas and brain infarction were common findings in the acute stage of the disease. CT scan, allowing the detection and follow-up of cerebral manifestations of tuberculosis, proved to be an accurate and effective diagnostic method, which should be used in all cases of tuberculous meningitis.

Acute Disease↗
PubMedDate not supplied

Effects of ethanol on platelet function.

To obtain evidence for an ethanol mediated disruption of hemostasis we compared the effects of acute and chronic ethanol ingestion on platelet reactivity. Since ADP may be important for hemostasis in vivo it was used to induce platelet aggregation in platelet-rich plasma. Thromboxane B2 (TXB2) formed during the aggregation was measured by radioimmunoassay. Ethanol (1.5 g/kg) given to 8 healthy non-alcoholic male volunteers increased platelet reactivity to ADP and the associated TXB2 formation rose from 289 +/- 60 (mean +/- SE) to 984 +/- 263 fmol/10(7) platelets (p less than 0.025). The effects lasted for as long as ethanol was present in blood. In 13 non-cirrhotic male alcoholics the withdrawal of ethanol caused a 4-fold increase in TXB2 formation within one week but the basal levels before ethanol withdrawal were the same as in controls. These findings are discussed in relation to the higher risk of brain infarction seen in alcoholics and even associated with binge drinking. Further studies are needed to establish the effects of ethanol on prostacyclin formation.

Adenosine Diphosphate↗
PubMed1988

Wind-chill and the seasonal variation of cerebrovascular disease.

The hospital admission rates for patients with specific types of stroke were examined for seasonal variation and correlation with meteorological factors. A seasonal variation in admission rates was found for subarachnoid haemorrhage, thrombo-embolic brain infarction and ill-defined cerebrovascular disease. Overall this seasonality was more strongly associated with the computed chilling effect of the atmosphere than with changes in temperature, humidity or wind speed alone. No seasonal variation was observed for admission rates of intracerebral haemorrhage, transient ischaemic attack or occlusion of precerebral arteries. Intracerebral haemorrhage admission rates exhibited a decrease with time. This evidence suggests that seasonal variation in admission rates exists only for certain pathological types of stroke and this is strongly associated with changes in the chilling effect of the atmosphere.

Adult↗
PubMed2006

Benefit versus risk in statin treatment.

The Statin Safety Assessment Conference of the National Lipid Association (NLA), reported in this supplement to The American Journal of Cardiology, provides a comprehensive evaluation of old and new experience on adverse events associated with the 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, or statins. To place these in context, one can express both the risk of side effects and the benefits for cardiovascular disease in terms of events per person-year of statin treatment. The mortality risk from fatal rhabdomyolysis is approximately 0.3 per 100,000 person-years, and the risks of nonfatal rhabdomyolysis and of putative statin-attributable peripheral neuropathy are approximately 3 and 12 events, respectively, per 100,000 person-years. Reports of acute liver failure and acute or chronic kidney disease give lower rate estimates that, even when corrected for underreporting, are approximately equal to the background rates of these conditions in the general population, lending scant support for statin-attributable etiology. In contrast, the benefit of statin use is to avert several hundred deaths and several hundred cases each of heart and brain infarction per 100,000 person-years in appropriately treated high-risk patients. Although population estimates such as these are useful, they must be translated repeatedly to individual patient-provider encounters, where clinical skill and art must combine with scientific evidence. The continued publication of individual case reports and small randomized trials among groups of patients with potential side effects should be encouraged. Statins should not be used in situations where minimal benefit is expected, as safety data and risk-benefit analysis must be meshed with guidelines that help the clinician decide whom to treat and how aggressively to treat.

Coronary Artery Disease↗
PubMed2006

Coma might not preclude emergency operation in acute aortic dissection.

BACKGROUND: Syncope or new onset focal neurologic deficits are described in as many as one fifth of patients with acute aortic dissection referred for surgery. Coma or stroke caused by involvement of the arch vessels and secondary brain malperfusion is considered a major contraindication for emergency aortic repair. Initial experience with emergency operation in selected patients with acute type A aortic dissection complicated by coma is described. METHODS: Five comatose (median Glasgow coma score, 5.5), hemodynamically stable (systolic blood pressure > or = 100 mm Hg) patients with preserved pupillary reactivity and coma duration of less than 12 hours underwent emergency surgical repair. The ascending aorta was always replaced using profound hypothermic circulatory arrest. RESULTS: There were no operative deaths. No hemorrhagic brain infarction developed postoperatively. Ischemic strokes were documented by radiology in 3 patients, and were always right-sided. Four patients returned to normal life with no neurologic sequelae, whereas 1 patient showed partially recovered left hemiparesis and mild cognitive impairment. CONCLUSIONS: Coma may not represent an absolute contraindication for resuscitative surgery in hemodynamically stable patients with acute type A aortic dissection. A larger experience is necessary to draw more definitive conclusions.

Acute Disease↗
PubMed2004

Effects of berberine on potassium currents in acutely isolated CA1 pyramidal neurons of rat hippocampus.

The effects of berberine, an isoquinoline alkaloid with antiarrhythmic action, on voltage-dependent potassium currents were studied in acutely isolated CA1 pyramidal neurons of rat hippocampus by using the whole-cell patch-clamp techniques. Berberine blocked transient outward potassium current (IA) and delayed rectifier potassium current (IK) in a concentration-dependent manner with EC50 of 22.94+/-4.96 microM and 10.86+/-1.06 microM, Emax of 67.47+/-4.00% and 67.14+/-1.79%, n of 0.77+/-0.08 and 0.96+/-0.07, respectively. Berberine 30 microM shifted the steady-state activation curve and inactivation curve of IA to more negative potentials, but mainly affected the inactivation kinetics. Berberine 30 microM positively shifted the steady-state activation curve of IK. These results suggested that blockades on K+ currents by berberine are preferential for IK, and contribute to its protective action against ischemic brain damage.

Animals↗
PubMed2004

Mediation of BMP7 neuroprotection by MAPK and PKC IN rat primary cortical cultures.

We have previously demonstrated that pretreatment with bone morphogenetic protein 7 (BMP7), a trophic factor in the TGFbeta superfamily, reduces ischemia-induced brain infarction induced by middle cerebral artery ligation in rats. Since the mitogen-activated protein kinase (MAPK) pathway is involved in many TGFbeta-mediated responses, we examined the interaction of BMP7 and MAPK in primary cultures obtained from the cerebral cortex of E16-17 rat embryos. Lactate dehydrogenase (LDH) in the media was used as an index of cell death. BMP7 did not alter LDH levels at low concentration (1.25 nM), but exhibited increased cellular toxicity at higher concentration (>12.5 nM). BMP7 at the low concentration significantly attenuated H2O2-induced increases in LDH activity and decreases in neuronal density. Pharmacological interactions were used to examine if MAPK was involved in this response. BMP7-induced protection was antagonized by the p42,44 MAPK kinase inhibitors PD98059 and U0125. The p38 MAPK antagonist SB203580, and their inactive analog SB202474, also attenuated BMP7-induced protection, suggesting that the interaction with p38 MAPK is nonspecific. Previous studies have indicated that SB202474 has inhibitory effects on other protein kinases. We found that the protein kinase C inhibitor chelerythrine antagonized BMP7-induced protection against H2O2. Western blot analysis indicated that BMP7 increased phosphorylation of p42,44 MAPK and PKC. Taken together, our data suggest that BMP7 is neuroprotective at low concentrations in primary cortical cell culture. The protective effects of BMP7 may involve the activation of p42,44 MAPK and PKC.

Animals↗
PubMed2005

Fluoxetine and recovery of motor function after focal ischemia in rats.

Neuroprotective therapies and tissue plasminogen activator (t-PA) have limited application for most stroke patients and thus rehabilitation is the primary treatment option for improving recovery of function. Following brain injury, environmental enrichment, pharmacological and rehabilitative treatments can markedly alter neuronal plasticity and behavioral recovery even when delayed by several weeks after the insult. Fluoxetine has been given to stroke patients to combat depression but its effects on recovery of function are not known. Functional magnetic resonance imaging reveals that fluoxetine alters brain activity and modulates motor performance in stroke patients in a use-dependent fashion. Several antidepressants, including fluoxetine, increase growth factors and other proteins associated with plasticity, such as brain-derived neurotrophic factor (BDNF). In this study, we examined whether chronic administration of fluoxetine combined with rehabilitation affected recovery of function on 3 separate tests of forelimb reaching, preference and limb coordination after focal ischemia in rats. Ischemia was induced in male Long-Evans rats by intracortical and striatal injections of endothelin-1. Fluoxetine (10 mg/kg/day) combined with rehabilitation therapy (6 h/day) for 4 weeks did not alter the degree or rate of recovery of function compared to non-treated animals. Despite the ability of fluoxetine to alter brain activity and increase growth factors, it does not appear to be an effective pharmacological adjunct to functional recovery after ischemia in rats.

Analysis of Variance↗
PubMed2006

Transient ischemia-induced changes of interleukin-2 and its receptor beta immunoreactivity and levels in the gerbil hippocampal CA1 region.

Interlukin-2 (IL-2) is an important cytokine in the brain: IL-2 and its receptors are involved with inflammatory processes. Chronological changes in IL-2 level in serum, and IL-2 and its receptor (IL-2 receptor beta, IL-2Rbeta) immunoreactivities and levels were examined in the hippocampal CA1 region after transient forebrain ischemia in gerbils. IL-2 level in serum significantly decreased 12 h after ischemia/reperfusion. IL-2 immunoreactivity was detected in the somata of pyramidal cells in sham-operated group. At 15 min after ischemia, IL-2 immunoreactivity was shown in non-pyramidal cells as well as pyramidal cells. One day after ischemia, IL-2 immunoreactivity was lowest, and IL-2 immunoreactivity is shown in non-pyramidal cells from 2 days after ischemia. Four days after ischemia, IL-2 immunoreactivity was shown in dying pyramidal cells. IL-2Rbeta immunoreactivity in the sham-operated and 15 min-3 min post-ischemic groups is detected in the cell membrane of pyramidal cells. From 3 h after ischemia, IL-2Rbeta immunoreactivity is found in cytoplasm and nuclei, but not in cell membrane. IL-2Rbeta immunoreactivity decreases from 6 h after ischemia and is shown mainly in non-pyramidal cells from 3 days after ischemia. The data of Western blot analyses for IL-2 and IL-2Rbeta was similar to the immunohistochemical data. IL-2 infusion into cerebrospinal fluid did not protect hippocampal neurons from ischemic damage. These results suggest that IL-2 and IL-2Rbeta show malfunction from 3 h after ischemia, and exogenous IL-2 does not protect ischemic neuronal damage.

Animals↗
PubMed2006

Lithium-induced activation of Akt and CaM kinase II contributes to its neuroprotective action in a rat microsphere embolism model.

Lithium used in bipolar mood disorder therapy protects neurons from brain ischemic cell death. Here, we documented that lithium administration under microsphere-embolism (ME)-induced brain ischemia restored decreased protein kinase B (Akt) and Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) activities 24 h after ischemia in rat brain. Akt activation was associated with increased phosphorylation of its potential targets forkhead transcription factor (FKHR) and glycogen synthase kinase-3beta (GSK-3beta). In parallel with decreased CaMKII autophosphorylation, we also found marked dephosphorylation of tau proteins 24-72 h after ME. Increased protein phosphatase 2A (PP2A) activity was found 24 h after ME. Inhibition of increased PP2A activity by lithium treatment apparently mediated restored tau phosphorylation. Taken together, activation of Akt and CaMKII by lithium was associated with neuroprotective activity in ME-induced neuronal injury.

Animals↗