Influence of an increased intracranial pressure on cerebral and systemic haemodynamics during endoscopic neurosurgery: an animal model.

BACKGROUND: During endoscopic neurosurgery, direct mechanical stimulation of the brain by the endoscope and increased intracranial pressure (ICP) caused by the continuous rinsing can induce potentially lethal haemodynamic reflexes, brain ischaemia, and excessive fluid resorption. METHODS: In a newly presented rat model of endoscopic neurosurgery, stereotactic access to the cerebrospinal fluid was secured and the ICP was increased by controlled infusion until complete suppression of the cerebral perfusion pressure (CPP). The haematocrit (Hct) level was determined before and after the procedure. During the whole procedure, invasive arterial pressure, ICP, and heart rate were continuously recorded and evaluated in a subsequent offline analysis. After the procedure, the animals were allowed to recover and 7 days later they were killed for histological examination. RESULTS: Suppression of the CPP resulted in a severe hypertension combined with tachycardia or mild bradycardia. The Hct decreased from 41 to 35 over the minutes of CPP suppression. After cessation of the infusion, the ICP decreased to 37% of the plateau pressure within 2.5 s. In the first few minutes after restoration of normal ICP, five animals died because of pulmonary oedema. CONCLUSIONS: Upon complete suppression of the CPP, an obvious hypertension developed, often together with tachycardia, but no severe bradycardia. At high ICP levels, we observed an important translocation of irrigation fluid to the vascular space. Fatality was not caused by ischaemia or arrhythmia but due to pulmonary oedema.

Experimental thromboembolic stroke studied by positron emission tomography: immediate versus delayed reperfusion by fibrinolysis.

Acute obstruction of the middle cerebral artery (MCA) was obtained by injecting a single autologous blood clot into the internal carotid artery of dogs. The technique induced very reproducible unilateral ischemic lesions in the MCA territory; hemorrhagic transformation of the lesions was often seen. The hemodynamic and metabolic effects of blood clot embolism were studied in 35 dogs with positron emission tomography (PET) and the 15O steady-state technique, and compared with a control group of seven intact animals. In the acute phase, the involved brain tissue still had a nearly normal oxygen consumption (-11%) despite the lowered tissue perfusion (-20%) caused by the vascular obstruction. The lowered oxygen availability was compensated by an increased oxygen extraction ratio (+11%). Twenty-four hours after the insult, the hemodynamic situation had barely changed, and the ischemic event had evolved into a brain infarct in which oxygen consumption was clearly lowered (-25%) and accompanied by a significant lowering (-22%) of the oxygen extraction ratio compared with the acute situation. Therapeutic thrombolysis by local administration of streptokinase (500,000 IU), starting 30 min after the insult, was not able to salvage any brain tissue or to ameliorate tissue perfusion despite angiographically confirmed clot lysis. However, when fibrinolytic therapy was started within the first 5 min after the insult, hemispheric blood flow was normalized, and most of the threatened brain tissue was salvaged, as was indicated by its normalized oxygen consumption and oxygen extraction ratio. Early fibrinolysis was accompanied by definite clinical improvement and substantial reduction in the severity of the morphological lesions that were never hemorrhagic.

Effect of flunarizine and methylprednisolone on functional recovery after experimental spinal injury.

The effect of flunarizine and methylprednisolone on the recovery of somatosensory evoked potentials (SEPs) was evaluated in an experimental model of spinal cord impact injury in anesthetized cats. In addition, the effect of flunarizine on posttraumatic spinal cord blood flow (SCBF) (using the hydrogen clearance technique) and interstitial calcium and potassium activity (ion-selective electrodes) was investigated. After the injury (600 g.cm), SEPs disappeared, followed by a spontaneous recovery to 17% of the preinjury amplitude at the end of the 4 h observation period. Flunarizine treatment (0.1 mg/kg IV, given 5 and 120 min after injury) resulted in a significantly improved recovery of SEPs, reaching 52% of the preinjury amplitude. Methylprednisolone treatment (30 mg/kg IV, given 5 min after injury) resulted in a 30% recovery level, significantly better than in untreated animals but significantly inferior to flunarizine treatment. Combination of both treatments resulted in a 62% recovery level, significantly better than after methylprednisolone treatment alone. Flunarizine treatment had no significant effect on the postinjury evolution of SCBF and interstitial potassium activity; it did, however, significantly accelerate the recovery of interstitial calcium activity, which sharply decreased immediately after injury. It is concluded that intravenous administration of the calcium entry blocker flunarizine improves the functional recovery of the spinal cord in the acute phase after experimental spinal impact injury. The observed improvement is not achieved by an effect on local blood flow but is possibly related to an inhibitory effect of the drug on cellular calcium entry.

Borderline or malignant ovarian tumour? A case report of decision making with morphometry.

A young woman presented with bilateral ovarian tumours. Multiple sections of each tumour were shown to many pathologists for consultation; some considered the tumours to be borderline, whereas others thought that one or both of them was malignant. Morphometry showed that the numerical classification probabilities for borderline tumour were 0.78 for the left ovarian tumour and 0.85 in the right. The lesions were therefore regarded as borderline tumours and no additional chemotherapy was given. Three years after the second operation the patient is alive and well without clinical or biochemical evidence of recurrence. Most patients with borderline tumours who die from the disease do so in the first two years after the operation. This young patient was prevented from severe overtreatment by the application of morphometry, illustrating its use in this area of diagnostic gynaecopathology.

Effects of flunarizine on induced calcium transients as measured in fura-2-loaded neurons of the rat dorsal root ganglion.

The effect of the calcium entry blocker flunarizine on a high-potassium induced increase of intracellular free calcium was studied. The experiments were done with neurons isolated from rat dorsal root ganglia and loaded with the calcium-sensitive dye fura-2. The increase of calcium induced by 60 mmol/l potassium was abolished after removal of extracellular calcium, was reversibly reduced by 50 mumol/l cadmium (76% inhibition), 50 mumol/l nickel (25% inhibition) and 10 mumol/l nifedipine (18% inhibition), and reversibly increased after removal of extracellular sodium (26% increase). The potassium induced increase of intracellular calcium is, therefore, mediated by transmembrane calcium influx, probably to a large extent through cadmium-sensitive calcium channels. Flunarizine (5 min incubation followed 1 min wash-out) reduced the amplitude of the high-potassium induced calcium increase in a dose-dependent manner (Kd = 370 +/- 100 nmol/l; mean +/- SEM; n = 8), causing complete inhibition at a concentration of 10 mumol/l in the majority of cells. Flunarizine (> or = 1 mumol/l) caused a reversible increase of the resting level of intracellular calcium in some cells, an effect which disappeared in the absence of extracellular calcium. The drug (1 mumol/l had no influence on the time course of recovery of intracellular calcium subsequent to a rise induced by high-potassium or by the calcium ionophore A23,187. It is concluded that flunarizine acts as an inhibitor of depolarization-mediated calcium influx. At a concentration of 1 mumol/l, the drug presumably has no effect on cellular calcium extrusion and/or sequestration mechanisms.

In vivo evaluation of 4-[123I]iodo-N-[2[4-(6-trifluoromethyl-2-pyridinyl)-1-piperazinyl]ethyl]benzamide, a potential SPECT radioligand for the 5-HT1A receptor.

4-[123I]Iodo-N-[2-[4-(6-trifluoromethyl-2-pyridinyl)-1-piperazinyl]ethyl]benzamide (1.123I), a potential SPECT 5-HT(1A) radioligand, was evaluated in vivo in rats. Biodistribution studies were performed leading to a % ID in the brain of 0.22 at 5 min p.i. No significant differences in % ID/g tissue of the different isolated brain regions (hippocampus, hypothalamus, striatum, cortex and cerebellum) could be demonstrated. Blocking experiments with 8-OH-DPAT, WAY100635 and ketanserin could not show any significant change in tracer uptake in the isolated brain regions. These data suggest that uptake in the brain does not represent binding of 1.123I to the 5-HT(1A) receptor.

Design of a multiblock phantom for radiotherapy dosimetry applications.

This note describes the design of a multiblock semi-anatomic phantom, which lends itself to a variety of radiotherapy dosimetry applications, in particular, the audit of external beam treatment planning and delivery. The basic building blocks of the phantom were formed from a variety of tissue substitute materials and could be assembled in many ways to model different cross-sections through the body.

Cardiocirculatory adjustments during pregnancy -- an echocardiographic study.

Adaptation of the circulation to pregnancy occurs via a complicated series of changes not yet completely understood. To define pertinent alterations, echocardiographic measurements of left ventricular function were performed every 4 weeks in 13 normal pregnant women. Six weeks postpartum each women was reexamined; thus each woman served as her own nonpregnant control. Left ventricular dimensions, left venticular wall thickness, shortening fraction, and rate of change of these measurements were recorded. As expected, cardiac output was increased throughout pregnancy. Up to 20 weeks gestation this occurred via an increased heart rate. After 20 weeks gestation stroke volume increased significantly, with 20% at 20--26 weeks up to 30% at term (p < 0.01). With the end-diastolic wall thickness remaining equal, myocardial hypertrophy occurred. This was corroborated by an increase in end-systolic left ventricular wall thickness towards term: from 13.8 mm (S.D. +/- 1.73) in early pregnancy to 16.6 mm (S.D. +/- 1.62) at term, with end-systolic left ventricular dimension unchanged. It was concluded that during pregnancy the mechanism to produce a higher cardiac output shifts from an increase in cardiac frequency to elevation of stroke volume with concomitant myocardial hypertrophy. Due to changes in heart rate and afterload, no conclusions could be drawn regarding myocardial contractility.

[Hemodynamic adaptations in proximal cerebrovascular occlusion]. / Hemodynamische aanpassingen bij proximale cerebrovasculaire occlusie.

In order to gain more insight into the pathophysiology of extracerebral cerebrovascular occlusion, the cerebral hemodynamic behaviour after uni- or bilateral carotid occlusion was investigated. In Wistar rats, acute occlusion of one common carotid artery leads to a moderate bilateral lowering of the resting hemispheric brain blood flow; no interhemispheric perfusion asymmetry is observed. During hypercapnia, however, a manyfold increase of the hemispheric blood flow is seen at the intact side, whereas blood flow increase at the side of the occlusion is suppressed indicating that the cerebrovascular reserve at the side of the occlusion is largely used to preserve resting hemispheric perfusion. During the days (1, 5, 15 and 30) following the occlusion, resting hemispheric blood flow is progressively restored rather rapidly (bilateral normalization on the fifth day) whereas restoration of the cerebrovascular reserve (hemispheric blood flow increase in hypercapnia) proceeds more slowly and a nearly normal hypercapnic response is reached on day thirty. Spontaneously Hypertensive Rats (SHR) show structural abnormalities of their blood vessels during the development of hypertension, leading to impaired adaptation possibilities of the cerebral vasculature after unilateral common carotid occlusion. This is indicated by the striking comparability of the compensation of hemispheric cerebral blood flow (in normo- and hypercapnia) of SH rats five days after unilateral carotid occlusion with the cerebral hemodynamic status of normotensive animals already seen 24 hours after the same occlusion. Consecutive bilateral common carotid occlusion shows that survival rate increases by increasing the interval between both occlusions. This survival relation is much more unfavorable in SH rats. The parallelism between the restoration of the measured CO2-reactivity of the blood flow in the involved hemisphere after unilateral carotid occlusion and the evolution of survival rate after consecutive bilateral carotid occlusion indicates that the response of the hemispheric circulation to CO2 offers a good estimate of true cerebrovascular reserve after cerebrovascular accidents of this kind. In cats, acute bilateral occlusion of the carotid arteries leads to a moderate decrease of resting cerebral blood flow in the anterior parts of the brain (cerebrum); the hypercapnic response of this region is, however, completely abolished. In the posterior brain regions (medulla oblongata and cerebellum) resting blood flow and its increase under hypercapnia are preserved. The experiments indicate that the relative preservation of resting cerebral blood flow in the cerebrum of the cat after acute bilateral carotid occlusion is at the expense of its complete hemodynamic reserve. Posterior brain regions are better protected in these conditions.(ABSTRACT TRUNCATED AT 400 WORDS)

[The use of radionuclides, specifically positron-emission tomography, in the determination of the blood circulation and metabolism of the brain. Application in experimental cerebral embolism]. / Gebruik van radionucliden, in het bijzonder positronenemissietomografie bij het bepalen van de doorbloeding en het metabolisme van de hersenen. Toepassing bij experimentele hersenembolie.

The introduction of positron emission tomography (PET) to study the cerebral circulation and metabolism is for the present the last step in the evolution of a technology which started 40 years ago with the gas clearance method developed by Kety and Schmidt. To study cerebral blood flow and metabolism in humans the steady state 15O method (Frackowiak et al., 1980) is widely used in different PET centers. We have used this method in experimental animals. The principles of the method and the mathematical models which are at the basis of the calculation of cerebral blood flow (CBF) and oxygen metabolism (cerebral metabolic rate for oxygen, CMRO2 and oxygen extraction ratio, OER) are relatively simple but during its application in vivo several problems arise as described. The steady state method of Frackowiak et al. allowed in our experiments the accurate measurement of cerebral blood flow and oxygen metabolism in anesthetized dogs. We have investigated the effect of experimental cerebral embolism in different series of experiments. Two different models of cerebral ischemia were assessed. In the first model focal ischemia was produced by infusing Sephadex particles (mean diameter 40 microns) into the left common carotid artery; in the second model an autologous blood clot (100 microliters) was injected into the left internal carotid artery. With both procedures the ischemia was practically limited to the ipsilateral hemisphere. Moreover in the two models the effects of ischemia were very reproducible. This is probably due to the good standardization of the embolization procedures. The results clearly indicate a differential effect of microembolization with particles and blood clot embolization, illustrating the importance of the technique used to produce cerebral embolization in experimental animals. PET offers possibilities for diagnosis of cerebral ischemia. At variance with the classical techniques for studying cerebral blood flow PET also allows simultaneous assessment of cerebral metabolism and to differentiate between brain tissue which is irreversible damaged and tissue which can be potentially salvaged. Therefore PET also offers new possibilities in clinical and experimental research. The reproducible effects obtained with the blood clot model, the metabolic cerebral effects of which are similar to those of clinical stroke, will allow to study the effect of different therapeutic approaches for stroke such as thrombolysis and calcium entry blockade.

Bovine spastic paralysis: results of surgical desafferentation of the gastrocnemius muscle by means of spinal dorsal root resection.

A dorsal laminectomy of L-4, L-5, and L-6, followed by resection of the dorsal (afferent) roots of the gastrocnemius muscle (desafferentation) was performed on 3 calves which had spastic paralysis. All signs of the condition disappeared after desafferentation. This suggests an overactive stretch reflex to be the cause of the spastic paralysis.

Bovine spastic paralysis: cerebrospinal fluid concentrations of homovanillic acid and 5-hydroxyindoleacetic acid in normal and spastic calves.

Homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA) concentrations were determined in the cerebrospinal fluid (CSF) of 28 normal calves and 29 spastic calves. Concentrations of HVA were significantly (P less than 0.01) lower in spastic calves, whereas differences in 5-HIAA concentrations were not found between normal and spastic calves. These findings indicate that a lower dopaminergic metabolism takes place in the central nervous system (CNS) of spastic calves.

[Acute acalculous cholecystitis associated with primary antiphospholipid antibody syndrome. Cure with low-molecular-weight heparin and antivitamin K]. / Cholécystite aiguë alithiasique associée à un syndrome primaire des anti-phospholipides. Guérison sous héparine de bas poids moléculaire et anti-vitamine K.

We report the first case of acute acalculous cholecystitis associated with primary antiphospholipid-antibody syndrome. The diagnosis was serological and was based on positive tests for lupus anticoagulant or anticardiolipin antibodies. The treatment was exclusively medical. Cholecystitis was cured with low-molecular weight heparin and oral anticoagulants. A rapid diagnosis can prevent lack of therapeutic errors such as surgery, antibiotherapy or corticotherapy, and long-term anticoagulant treatment can be proposed to prevent recurrent thrombosis.

[Value of rectosigmoidoscopy with bacteriological culture of colonic biopsies in the diagnosis of post-antibiotic hemorrhagic colitis related to Klebsiella oxytoca]. / Intérêt de la rectosigmoïdoscopie avec culture bactériologique de biopsies coliques dans le diagnostic des colites hémorragiques post-antibiotiques associées à Klebsiella oxytoca.

UNLABELLED: We report 7 cases of antibiotic-associated and hemorrhagic colitis due to Klebsiella oxytoca. The diagnosis was performed by sigmoidoscopy with bacteriological biopsy culture. PATIENTS AND METHODS: Nine patients, aged 25-83 years, were hospitalized from February 1993 to October 1995 with hemorrhagic acute diarrhea following antibiotic treatment: amoxicillin (n = 3). amoxicillin-clavulanic acid (n = 4), cephalosporine (n = 2). All patients have had two stool samples cultures including Clostridium difficile toxin detection. Sigmoidoscopy with collection of biopsy specimens for bacteriological cultures was performed routinely. RESULTS: Endoscopic findings established the diagnosis of colitis in all cases: rectitis (n = 1), diffuse left colitis (n = 4), segmental left colitis (n = 4). The lesions were erythematous and purpuric (n = 5) or ulcerative (n = 4). Stool culture was normal in all cases but Klebsiella oxytoca was isolated in 7 cases (78%). CONCLUSIONS: Sigmoidoscopy and bioptic microbiology ensured the diagnosis of antibiotic-associated hemorrhagic colitis due to Klebsiella oxytoca.

[Pancreatic involvement, ascites and diarrhea in idiopathic hypereosinophilic syndrome]. / Atteinte pancréatique, ascite et diarrhée au cours d'un syndrome hyperéosinophilique idiopathique.

We report a new case of idiopathic hypereosinophilic syndrome with multivisceral digestive failure. After an erroneous diagnosis of pancreatic cancer, the pathological examination of pancreaticoduodenectomy specimen demonstrated pancreatic fibrosis with eosinophilic infiltration without gastritis or duodenitis. The diagnosis of idiopathic hypereosinophilic syndrome was made three months later upon the classical criteria: a) blood eosinophilia of 1.5 G/L or more, persisting for more than 6 months; b) lack of evidence for any other recognised cause of eosinophilia: c) multiple organ systemic involvement: rheumatologic, cutaneous and digestive (pancreatitis, ascites and diarrhoea): d) previous history of allergic disease and increased plasmatic IgE levels; e) absence of leukemic markers. This case emphasises the difficulty in classifying eosinophilic infiltration of the gut and the possibility of transitional forms between eosinophilic gastro-enteritis and idiopathic hypereosinophilic syndrome. We argue that in case of eosinophilic infiltration of the gut, systematic research of multiple organ systemic involvement is mandatory.