Whole-genome sequencing in multiplex families with psychoses reveals mutations in the SHANK2 and SMARCA1 genes segregating with illness.

A current focus in psychiatric genetics is detection of multiple common risk alleles through very large genome-wide association study analyses. Yet families do exist, albeit rare, that have multiple affected members who are presumed to have a similar inherited cause to their illnesses. We hypothesized that within some of these families there may be rare highly penetrant mutations that segregate with illness. In this exploratory study, the genomes of 90 individuals across nine families were sequenced. Each family included a minimum of three available relatives affected with a psychotic illness and three available unaffected relatives. Twenty-six variants were identified that are private to a family, alter protein sequence, and are transmitted to all sequenced affected individuals within the family. In one family, seven siblings with schizophrenia spectrum disorders each carry a novel private missense variant within the SHANK2 gene. This variant lies within the consensus SH3 protein-binding motif by which SHANK2 may interact with post-synaptic glutamate receptors. In another family, four affected siblings and their unaffected mother each carry a novel private missense variant in the SMARCA1 gene on the X chromosome. Both variants represent candidates that may be causal for psychotic disorders when considered in the context of their transmission pattern and known gene and disease biology.

Efficacy of triple therapy with a proton pump inhibitor, levofloxacin, and amoxicillin as first-line treatment to eradicate Helicobacter pylori.

BACKGROUND: Triple therapy including a proton pump inhibitor, clarithromycin, and amoxicillin (PPI-CA) is the first-choice treatment used for H. pylori eradication. The efficacy of this treatment is declining of late, and alternative therapies are currently under evaluation. OBJECTIVES: To evaluate the efficacy, safety and compliance of a triple therapy with a PPI, amoxicillin and levofloxacin (PPI-LA)--replacing clarithromycin--for the eradication of H. pylori. METHODS: The study included 135 patients (65% women), mean age 53 years, with dyspeptic symptoms and H. pylori infection proven by a positive urease rapid test, histological analysis, or C13-urea breath test. DIAGNOSIS: non-investigated dyspepsia 48.9%, functional dyspepsia 36.3%, and ulcerative dyspepsia 14.8%. Treatment was indicated with a proton pump inhibitor at usual doses, amoxicillin 1 g, and levofloxacin 500 mg, administered jointly during breakfast and dinner for 10 days. We studied the performance of this triple therapy and its effects using a questionnaire, and effectiveness by the negativity of the C13-urea breath test after 6-8 weeks after treatment discontinuation. Per protocol, we compared the effectiveness of PPI-LA with a control group of 270 patients treated with PPI-CA for 10 days. RESULTS: 130 patients (96.2%) could complete the treatment and follow-up protocol. Effectiveness (intention to treat) was 71.8% (97/135) and 74.6% (per protocol) (97/130). Sixteen patients (11.8%) had well-tolerated adverse effects, except for 5 subjects (3.7%) who dropped out. PPI-CA was effective (per protocol) in 204 patients out of 270 (75.5%) in the control group. CONCLUSIONS: Triple therapy with a PPI, amoxicillin and levofloxacin for 10 days is a well-tolerated treatment that is easy to comply with; however it has low efficiency - less than 80% - and is not recommended as a first-choice treatment for H. pylori eradication. Similar results were obtained with the classic triple therapy using a PPI, clarithromycin and amoxicillin.

Comparison of methods for analysis of resveratrol in dietary vegetable supplements.

Resveratrol is a stilbene, which is one of a group of polyphenols in many plant foods. Interest in this substance lies in its potential health benefits. This study aimed to compare two different methods, chromatographic and constant-wavelength synchronous spectrofluorimetry, an alternative technique to determine the amount of resveratrol dietary supplements, as a model for more complex foods. High-performance liquid chromatography-photodyode array detector-mass spectrometry/mass spectrometry was used to confirm the results. The results obtained showed that both methods were valid for the determination of resveratrol in dietary supplements. HPLC with fluorescence and variable wavelength detectors offered better linearity and sensitivity, and would be more suitable for the determination of several stilbenes in complex samples. On the other hand, constant-wavelength synchronous spectrofluorimetry is a sensitive, rapid and inexpensive method that could be used for quick and precise determination when samples are expected to contain only one stilbene.

[Influence of nonsteroidal antiinflammatory drugs in gastrointestinal bleeding due to gastroduodenal ulcers or erosions in patients with liver cirrhosis]. / Influencia de los antiinflamatorios no esteroideos en la hemorragia digestiva por úlceras o erosiones gastroduodenales en pacientes con cirrosis hepática.

INTRODUCTION: Peptic ulcer disease, with or without complications, is more common in patients with liver cirrhosis than in the general population. Factors associated with portal hypertension are involved in its pathogenesis. The prevalence of Helicobacter pylori infection in patients with liver cirrhosis and the general population is similar. The aim of the present study was to determine the influence of nonsteroidal antiinflammatory drugs (NSAIDs) in the etiology of bleeding peptic ulcer disease in patients with liver cirrhosis. PATIENTS AND METHODS: We studied 35 patients with liver cirrhosis and gastrointestinal bleeding due to gastroduodenal ulcers or erosions (group A), 125 noncirrhotic patients with gastrointestinal bleeding due to gastroduodenal ulcers or erosions (group B), and 70 patients with liver cirrhosis who were admitted to hospital without gastrointestinal bleeding (group C). All patients were questioned about NSAID consumption, including aspirin, during the week prior to hospital admission. RESULTS: NSAID consumption was reported by 15 patients (42.8%) in group A, 102 patients (58.2%) in group B, and 6 patients (8.5%) in group C. Statistically significant differences were obtained when the results for group A were compared with those for group C. CONCLUSIONS: NSAID consumption in patients with liver cirrhosis without gastrointestinal bleeding was low (8.5%) and was much lower than that observed in patients with cirrhosis admitted to hospital for bleeding due to gastroduodenal ulcers or erosions (42.8%). As occurs in the general population, NSAIDs play a significant role in the pathogenesis of bleeding due to peptic ulcer disease in patients with liver cirrhosis and portal hypertension.

Modification of cyclin A expression by hepatitis B virus DNA integration in a hepatocellular carcinoma.

We have previously reported the identification of a hepatitis B virus (HBV) DNA integration in an intron of the cyclin A gene in an early hepatocellular carcinoma (HCC) and the isolation of human cyclin A cDNA. We have now constructed a cDNA library from the tumor and isolated several hybrid HBV-cyclin A cDNAs from it. The hybrid cDNAs encode an HBV-cyclin A fusion protein. In the chimeric protein, the N-terminus of cyclin A, including the signals for cyclin degradation, is deleted and replaced by viral PreS2/S sequences, transcription being initiated from the viral PreS2/S promoter. This chimeric protein is undegradable in an in vitro cyclin degradation assay. Northern blot analyses showed strong expression of the hybrid transcripts in the tumor, while cyclin A- or HBV-specific transcripts were not detected in the non-tumorous liver of the same patient. Thus, HBV DNA integration in the cyclin A gene resulted in a strong expression of hybrid HBV-cyclin A transcripts encoding a stabilized cyclin A. This chimeric protein may play an important role in the development of the tumor.

Overexpression of human cyclin A advances entry into S phase.

Cyclin A is a cell cycle regulatory protein that functions in mitotic and S-phase control in mammalian cells. Using a genomic construction corresponding to the human cyclin A gene under the control of its own promoter, we have established stable transfectants overexpressing cyclin A protein. Experiments assisted by laser scanning image cytometry showed that this overexpression begins from late G1 phase onwards and is therefore cell cycle-regulated in this model. We demonstrated that this overexpression advances entry into S phase, leading to a contraction of the overall cell generation time. These results provide evidence that cyclin A can be a rate-limiting factor with respect to the control of the transition to S phase in mammalian cells.

Differential expression of the cyclin-dependent kinase inhibitor P27 in primary hepatocytes in early-mid G1 and G1/S transitions.

P27, an inhibitor of cyclin-dependent kinases, plays an important role in the control of cell adhesion and contact inhibition-dependent cell cycle regulation. Hepatocytes, maintained in primary culture, offer a model of synchronized primary epithelial cells which retain a differentiated profile while stimulated to proliferate. We therefore investigated the pattern of endogenous p27 expression in cyclin rat hepatocytes isolated by collagenase perfusion followed by mitogenic stimulation. P27 was expressed in whole normal liver and freshly isolated hepatocytes. We then observed a sharp decrease in p27 levels, concomitant with the progression in early-mid G1, followed by reaccumulation in late G1 and the G1/S transition. Immunochemistry and BrdU labelling demonstrated nuclear localization of p27 and its expression in cells engaged in both G1 and S phase. P27 was detected in late G1 in complexes containing cyclins D1, E and A. Cyclin E- and A-associated kinase activities, however, were detected at the G1/S transition and depletion experiments confirmed that most active complexes were free of p27. Phosphorylated forms of p27 were detected in unstimulated and stimulated hepatocytes in both early-mid G1 and G1/S. Finally, two-dimensional gel electrophoresis showed evidence for several forms of p27 with a distinct profile of distribution in quiescent and stimulated hepatocytes. Collectively, our data offer a model in which p27 shows a biphasic profile of accumulation, with the early decrease possibly involved in the progression through early and mid G1. In contrast with most cell types tested so far, the late G1 accumulation did not impair formation of active cyclin E- and A associated kinases, and thus G1/S transition.

The involvement of human-nuc gene in polyploidization of K562 cell line.

During megakaryocyte differentiation, the immature megakaryocyte increases its ploidy to a 2(x) DNA content by a process called endomitosis. This leads to the formation of a giant cell, the mature megakaryocyte, which gives rise to platelets. We investigated the role of human-nuc (h-nuc), a gene involved in septum formation in karyokynesis in yeast, during megakaryocytic polyploidization. Nocodazole and 12-O-tetradecanoylphorbol-13-acetate (TPA) were used to induce megakaryocytic differentiation in K562 cell line. The ploidy distribution and CD41 expression of treated K562 cells were evaluated by flow cytometry. Using quantitative reverse transcriptase polymerase chain reaction (RT-PCR), we analyzed the h-nuc mRNA expression on treated K562 cells. Mature megakaryocyte-like polyploid cells were detected at day 5-7 of treatment with nocodazole. TPA also had a similar effect on K562 cells, but it was much weaker than that of nocodazole. The analysis of ploidy of nocodazole-treated K562 cells showed that nocodazole preferentially induced polyploidization of K562 cell line with a pronounced increase of the cells 8N at day 7 of culture. Expression of CD41, a differentiation-related phenotype, was significantly induced by TPA after 7 days of treatment, showing that functional maturation was mainly induced by TPA. In contrast, there was no significant increase in CD41 expression in nocodazole-treated K562 cells, suggesting that polyploidization and functional maturation are separately regulated during megakaryocytopoiesis. RT-PCR analysis indicated that h-nuc mRNA increased after 72 hours in the presence of nocodazole, preceding the induction of polyploidization. Our data indicate that h-nuc might play a role in polyploidization during megakaryocytic differentiation via inhibition of septum formation.

Early modifications of gene expression induced in liver by azo-dye diet.

The expression and regulation of the phosphoenolpyruvate carboxykinase gene were not grossly modified by feeding rats a 3'-methyl-4-(dimethylamino)azobenzene-containing diet despite maximum expression of the L-type pyruvate kinase gene being dramatically reduced as early as the 24th hour of the carcinogenic diet. Inhibition of aldolase B mRNA synthesis occurred more slowly, being maximum at the 3rd day. After stopping administration of the carcinogen, a very rapid, but transient increase of the L-type pyruvate kinase mRNA was observed at the 24th hour, whereas aldolase B mRNA increased only slowly. The amount of aldolase A mRNA fell quickly after termination of carcinogen administration, levels being normal at the 2nd-3rd day. At this time, the histological structure of the liver was indistinguishable from that of animals still receiving the azo-dye diet. It appears, therefore, that in the rat both administration and withdrawal of the azo-dye carcinogen induce rapid modifications of the expression of some genes, before any cellular modification is distinguishable.

NOR-2 (neuron-derived orphan receptor), a brain zinc finger protein, is highly induced during liver regeneration.

Zinc-finger proteins are involved in several cellular processes. Some of these proteins are implicated in the primary cellular response in regenerating liver and mitogen-stimulated cells. Using a rat cDNA brain library, we have isolated a clone designated NOR-2, encoding a protein containing two zinc-finger motifs and whose expression is highly induced during G0/G1 transition. We analysed the expression of NOR-2 mRNAs during early growth in regenerating liver and in both insulin-stimulated H4-II cells and pheochromocytoma-derived cell line PC12 treated by NGF. In these systems, there is an early, rapid and transient accumulation of NOR-2 mRNAs. The induction of NOR-2 mRNAs does not require de novo protein synthesis, since it is not prevented by cycloheximide treatment. Mobility shift assays show that NOR-2 protein binds to NBRE, a target sequence for r-NGFI-B family. Structurally, NOR-2 is closely related to the recently identified NOR-1 factor. Therefore, like NOR-1, NOR-2 belongs to the r-NGFI-B sub-family of nuclear receptors superfamily.

Detection of mRNAs present at low concentrations in rat liver by in situ hybridization: application to the study of metabolic regulation and azo dye hepatocarcinogenesis.

In situ hybridization on tissue sections was used to detect mRNAs present at low concentrations during metabolic adaptation and azo dye carcinogenesis in rat liver. The method consisted of hybridizing the slices at relatively high stringency with [35S]-labeled single-stranded probes derived from cDNA insert clones into the M13 phage. L-pyruvate kinase mRNA was proved to be present at very low concentrations in hepatocytes of fasted rats and to be relatively abundant in all hepatocytes after 18 hr of refeeding on a carbohydrate-rich diet. Aldolase A mRNA concentrations have been previously shown to increase markedly in liver of 3'-methyl DAB-fed rats, with a maximum at the fourth week. We demonstrate here, using our in situ hybridization technique, that this phenomenon is not due to re-expression of this "fetal marker" in hepatocytes but to its abundancy in proliferating small cells (i.e., so-called oval and transitional cells). Small amounts were also detected in sinusoidal cells. In normal liver, aldolase A mRNAs were detected only in some sinusoidal cells.

Physical state abnormality of erythrocyte membrane in myotonic dystrophy: a spin label study.

Biophysical abnormalities of the erythrocyte membrane in muscular dystrophies have been described by numerous authors. This work presents the results we have obtained on 23 subjects suffering from myotonic muscular dystrophy (MyD, Steinert disease) by the spin label method. Two types of fatty acid spin labels were used: 5-nitroxide stearic acid (5NS) and 16-nitroxide stearic acid (16NS) which probe the membranes respectively near their polar heads and in their hydrophobic core. We measured the classical order parameter, the saturation behaviour of the electron paramagnetic resonance signal, and the label apparent rotation correlation time as a function of the temperature, on fresh and in vitro stored red blood cells. With the 5NS label, no differences were found between controls and patients. With the 16NS label, a highly significant variation in the thermic behaviour of the membrane is observed in its hydrophobic and fluid core. This last result may suggest some similarities between the red blood cell membranes of adult MyD's and healthy children.

A spin label study of the erythrocyte membrane in mothers and sisters of patients suffering from Duchenne muscular dystrophy.

The erythrocyte membranes of mothers and sisters of boys suffering from Duchenne Muscular Dystrophy (DMD) have been studied by spin labelling. Two oxazolidine nitroxide derivatives of stearic acid were used. With the first of them (16 NS) which probes the hydrophobic part of the phospholipids, we measured the fluidity of the membrane as a function of temperature. The second nitroxide derivative (5 NS) probes the membrane near the phospholipid polar heads. The amplitude of the electron spin resonance signal was studied as a function of the spectrometer microwave power in order to determine the paramagnetic label saturation behaviour. No significant difference was observed between the control adult women and the carrier mothers. On the contrary, almost all the normal young premenarchial girls showed simultaneously a break in the fluidity vs. temperature plot of the 16 NS probe and a saturation phenomenon of the 5 NS label signal. In about 50% of the DMD boys' sisters, no break in the temperature plot nor saturation behaviour was observed. This corresponds to the theoretical repartition between normal and carrier girls if one admits that about 30% of the latter do not have any detectable membrane abnormality, as in the case of the creatine kinase (CK) test which shows about 30% of normal levels in carrier women. The study of the erythrocyte membrane in young girls can then be an useful complementary tool to detect DMD carriers.

Comparison of the clinical presentation of symptomatic arteriovenous malformations (angiographically visualized) and occult vascular malformations.

The authors compared the clinical presentations of angiographically apparent arteriovenous malformations (AVMs) and angiographically occult vascular malformations (AOVMs) of the brain in 188 consecutive patients treated when computed tomography and magnetic resonance were available. There were 133 patients (70.7%) with AVMs and 55 patients (29.2%) with AOVMs. AOVMs tended to occur more frequently in male patients and in the posterior fossa and to present earlier clinically than AVMs, but differences were not significant. One distinctive feature was the greater size of AVMs, as compared with AOVMs. Presentation by hemorrhage occurred in 64.3% of the patients with AVMs and in 61.8% of those with AOVMs. Malformations of both types located in the posterior fossa presented with hemorrhage more frequently (84.2% of AVMs and 78.5% of AOVMs) than similar lesions lying above the tentorium (60.8% of AVMs and 56% of AOVMs). Bleeding was more severe in patients with AVMs than in those with AOVMs, as indicated by the higher mortality associated with hemorrhage (7.5 vs. 3.6% of the cases) and the more frequent and marked decrease in the level of consciousness observed at admission (34 vs. 16.2% of drowsy or comatose patients). Brain hematomas caused by AVMs were on average bigger than those caused by AOVMs (58.8 and 20% of large hematomas, respectively), and intraventricular and subarachnoid hemorrhages were also more common and profuse in patients with AVMs. However, AOVMs bled subsequently more times than AVMs (61.7 vs. 15.6%), before they were diagnosed and treated, leading to a higher nonoperative morbidity (16.3 vs. 13.6%).(ABSTRACT TRUNCATED AT 250 WORDS)

Spinal metastatic disease: analysis of factors determining functional prognosis and the choice of treatment.

The authors surveyed 31 surgical and radiotherapy series comprising over 2300 patients with spinal metastases to determine the influence of factors such as tumor biology and topography, pretreatment neurological status, the presence of a myelographic block, the progression rate of symptoms, and the general medical condition of the patient on both the functional prognosis and the choice of treatment. Both life expectancy and the functional results after therapy are mainly dependent on tumor biology, which in turn determines radiosensitivity. The remaining factors seem to have only complementary predictive power. Because radiotherapy has been found to be as effective as operation plus radiotherapy in the management of the majority of patients with spinal metastases, it is very important to improve the selection of surgical candidates (less than 42% of the total cases) to prevent unnecessary surgery-related morbidity and mortality. Factors considered important in the selection of therapy are the location of the tumor within the spinal canal, the neurological status at the time of treatment, and the systemic condition of the patient.

Percutaneous microcompression of the gasserian ganglion for trigeminal neuralgia.

The authors report 144 cases of trigeminal neuralgia treated by percutaneous microcompression of the trigeminal ganglion (PMTG). The operation was performed under short-lasting barbiturate anesthesia without endotracheal intubation. Meckel's cave was cannulated with a No. 4 Fogarty catheter and the balloon was inflated for 1 minute. The average intraluminal pressure required for adequate compression of the ganglion was about 1200 mm Hg. All patients were initially relieved of their neuralgia. In a follow-up period ranging from 6 months to 4 1/2 years, 14 patients (9.7%) developed recurrence of pain between 10 and 35 months after surgery. Eleven patients underwent a second PMTG. All nine early failures and 10 of the 11 late recurrences occurred in cases with technical deficiencies. Most of the minor surgical complications observed were also related to avoidable technical errors. There were no anesthetic complications and no deaths. All patients developed mild to moderate postoperative hemifacial numbness with or without objective hypesthesia. Both subjective and objective deficits gradually diminished with time and were well tolerated. One year after the operation nearly 40% of the patients still had patches of slightly decreased sensation in one or more trigeminal divisions and 16% had mild dysesthesia. Anesthesia dolorosa or keratitis was not reported. The PMTG procedure is easy to perform and requires a short operative time and a brief period of hospitalization. It is well tolerated by patients, who describe it as a totally pain-free experience. Morbidity is minimal and recurrence of neuralgia does not seem to be higher than with alternative procedures.

Dural posterior fossa AVM producing raised sagittal simus pressure. Case report.

A patient with raised intracranial pressure secondary to a dural arteriovenous malformation (AVM) of the posterior fossa is presented. Direct shunting of arterial blood into the transverse sigmoid sinus caused a considerable increase of the sagittal sinus pressure (SSP) and elevation of intracranial pressure (ICP). Both ICP and SSP returned to normal values following obliteration of the dural AVM by selective embolization.

Intraventricular morphine for control of pain in terminal cancer patients.

Satisfactory control of intractable pain has been achieved in 17 terminal cancer patients by injecting small doses of morphine into the lateral cerebral ventricle via an Ommaya reservoir. Pain relief together with a favorable behavioral response was obtained without interference with other sensory modalities, noticeable physical changes, or side effects annoying or severe enough for the patient to discontinue therapy. Eleven patients developed tolerance, but this phenomenon does not require withdrawal of treatment. Chronic intraventricular morphine administration can be safely performed on an outpatient basis, and results in control of midline, bilateral, and diffuse pain associated with orofacial and disseminated cancer. However, this experience is preliminary and further clinical trials are needed to determine the place of this method of therapy in the management of chronic pain.

Posttraumatic cerebral hemispheric swelling. Analysis of 55 cases studied with computerized tomography.

The authors have analyzed the clinical course and intracranial pressure (ICP) changes in 55 severely head-injured patients presenting with bulk enlargement of one cerebral hemisphere within a few hours after trauma. These patients represent 10.5% of a series of 520 patients with severe head injury studied with computerized tomography (CT). Cerebral hemispheric swelling has the highest mortality rate and the shortest survival period after trauma in all series of severe head injury. In this series, it was associated with an ipsilateral subdural hematoma of variable size in 47 patients (85%) or with a large epidural hematoma in five patients (9%); in three patients (5.4%) it occurred as an isolated lesion. Evacuation of an associated extracerebral hematoma, which was performed within 4 hours after injury in only 20% of cases, scarcely changed the patients' preoperative neurological status. The high incidence of arterial hypotension and/or hypoxemia at admission (47% of cases) and the severity of the clinical presentation (82% of patients scored 5 points or less on the Glasgow Coma Scale, 74% had unilateral or bilateral mydriasis, and 80% had an initial ICP above normal) correlated with a very poor final outcome (87% mortality). Only one of the 11 patients with normal initial ICP continued to have normal pressure throughout the course. High-dose thiopental failed to control severe intracranial hypertension in 24 patients (51%) who had a fulminant, malignant course. A transient decrease in ICP elevation was achieved in 15 patients (31.4%) and definitive control in eight patients (17%), among whom were the seven survivors in this series. In the authors' experience, once ICP is controlled, barbiturate administration should not be discontinued until a control CT scan shows complete disappearance of the mass effect.

Acute epidural hematoma: an analysis of factors influencing the outcome of patients undergoing surgery in coma.

Mortality due to epidural hematoma is virtually restricted to patients who undergo surgery for that condition while in coma. The authors have analyzed the factors influencing the outcome of 64 patients who underwent epidural hematoma evacuation while in coma. These patients represented 41% of the 156 patients operated on for epidural hematoma at their centers after the introduction of computerized tomography (CT). Eighteen patients (28.1%) died, two (3.1%) became severely disabled, and 44 (68.8%) made a functional recovery. The mortality rate for the entire series was 12%, significantly lower than the 30% rate observed when only angiographic studies were available. A significant correlation was found between the final result and the mechanism of injury, the interval between trauma and surgery, the motor score at operation, the hematoma CT density (homogeneous vs. heterogeneous), and the hematoma volume. The patient's age, the course of consciousness before operation (whether there was a lucid interval), and the clot location did not correlate with the final outcome. The mortality rate was significantly higher in patients operated on within 6 hours or between 6 and 12 hours after injury than in those undergoing surgery 12 to 48 hours after injury. Compared with the patients operated on later, the patients undergoing surgery in the early period were, on the average, older and had more rapidly developing symptoms, more pupillary changes, lower motor scores at surgery, larger hematomas, a higher incidence of mixed CT density clots, more severe associated intracranial lesions, and higher postoperative intracranial pressure (ICP). The mechanism of trauma seems to influence the course of consciousness before and after surgery. Passengers injured in traffic accidents had a lower incidence of a lucid interval and longer postoperative coma than patients with low-speed trauma, suggesting more frequent association of diffuse white matter-shearing injury. The duration of postoperative coma correlated with the morbidity rate in survivors. Forty-eight patients (75%) had one or more associated intracranial lesions, and 70% of these required treatment for elevation of ICP after hematoma evacuation. An ICP of over 35 mm Hg strongly correlated with poor outcome; administration of high-dose barbiturates was the only effective means for lowering ICP in nine of 15 patients who developed severe intracranial hypertension after surgery. This study attempts to identify patients at greater risk for presenting postoperative complications and to define a strategy for control CT scanning and ICP monitoring.