Local Hemodynamic Conditions Associated with Focal Changes in the Intracranial Aneurysm Wall.

BACKGROUND AND PURPOSE: Aneurysm hemodynamics has been associated with wall histology and inflammation. We investigated associations between local hemodynamics and focal wall changes visible intraoperatively. MATERIALS AND METHODS: Computational fluid dynamics models were constructed from 3D images of 65 aneurysms treated surgically. Aneurysm regions with different visual appearances were identified in intraoperative videos: 1) "atherosclerotic" (yellow), 2) "hyperplastic" (white), 3) "thin" (red), 4) rupture site, and 5) "normal" (similar to parent artery), They were marked on 3D reconstructions. Regional hemodynamics was characterized by the following: wall shear stress, oscillatory shear index, relative residence time, wall shear stress gradient and divergence, gradient oscillatory number, and dynamic pressure; these were compared using the Mann-Whitney test. RESULTS: Hyperplastic regions had lower average wall shear stress (P = .005) and pressure (P = .009) than normal regions. Flow conditions in atherosclerotic and hyperplastic regions were similar but had higher average relative residence time (P = .03) and oscillatory shear index (P = .04) than thin regions. Hyperplastic regions also had a higher average gradient oscillatory number (P = .002) than thin regions. Thin regions had lower average relative residence time (P < .001), oscillatory shear index (P = .006), and gradient oscillatory number (P < .001) than normal regions, and higher average wall shear stress (P = .006) and pressure (P = .009) than hyperplastic regions. Thin regions tended to be aligned with the flow stream, while atherosclerotic and hyperplastic regions tended to be aligned with recirculation zones. CONCLUSIONS: Local hemodynamics is associated with visible focal wall changes. Slow swirling flow with low and oscillatory wall shear stress was associated with atherosclerotic and hyperplastic changes. High flow conditions prevalent in regions near the flow impingement site characterized by higher and less oscillatory wall shear stress were associated with local "thinning" of the wall.

[Principles of revascularization in treatment of giant intracranial aneurysms].

During recent decades extra-intracranial and intra-intracranial bypasses have deserved high interest among neurosurgeon, especially in management of giant cerebral aneurysms. Development of microsurgery and neuroanesthesiological techniques, advances in neuroradiology and neurophysiology prerequisite improvement of revascularization surgery. Evolution of competitive endovascular methods pushes the surgeons to improve microneurosurgical technique of revascularization and elaboration of new approaches to management of intracranial aneurysms. In this review we discuss principles of surgery of cerebrovascular bypasses in management of giant aneurysms applied in our clinic.

Post-traumatic frontal and parieto-occipital extradural haematomas: a retrospective analysis of 41 patients and review of the literature.

BACKGROUND: The purpose of this study was to analyse the differences between patients with frontal (FEDH) or parieto-occipital (POEDH) epidural haematomas and evaluate possible statistically significant prognostic factors. MATERIAL AND METHODS: In this retrospective study of a group of 41 patients with a FEDH (17) or POEDH (24 individuals), the authors analysed the influence of gender, age, type of injury, clinical presentation, Glasgow coma scale (GCS) score on admission, radiological findings, and time interval from trauma to surgery on outcomes. A good recovery and moderate disability were considered a "good" or "favourable outcome", whereas severe disability, a vegetative state or death was a "poor outcome". RESULTS: In the POEDH subgroup, a higher GCS score on admission and a younger age were statistically significant prognostic factors for a better outcome (p=0.006, rs=0.702). In the subgroup of patients with FEDHs, the results were not significant. However, patients with FEDHs more frequently had "good outcomes" than members of the POEDH subgroup (88.2 vs. 70.9%). Children (≤ 18 years old) constituted a smaller portion of the POEDH subgroup (12.5%) than those in the FEDH subgroup (41.2%). The evaluation of time intervals between the accident and surgery (≤ 24 h vs. > 24 h) showed no significant influence on outcomes in any of the studied subgroups. However, patients undergoing surgery within 24 h of their injury had a less favourable GCS score on admission than those operated on more than 24 h after their injury. Subacute and chronic clinical courses predominated in patients with a FEDH (10/17 FEDH vs. 11/22 POEDH). Different accompanying intradural lesions occurred in 12 patients of the POEDH subgroup, but only in 2 of the FEDH subgroup (50 vs. 11.8%). However, the presence of such lesions did not significantly deteriorate surgical outcomes in either of the subgroups.

Microsurgical technique for previously coiled aneurysms.

Since the introduction of Guglielmi detachable coils to treat intracranial aneurysms in 1991, the number of patients undergoing endovascular coiling has continuously risen as well as the number of those residual and recurrent previously coiled aneurysms that necessitate a microsurgical occlusion. Between July 1995 and August 2009 we retrospectively analyzed 81 patients with 82 previously coiled aneurysms treated microsurgically at two Finnish Neurosurgical University Hospitals, Helsinki and Kuopio. Fifty-eight aneurysms (71%) were located at anterior circulation and 24 (29%) at posterior circulation. Fifteen patients were operated on within the first month (early surgery) after coiling, whereas 66 were treated later (late surgery). Complete or partial removal of coils during surgery may facilitate clipping, but is significantly (P<0.001) more difficult to accomplish in late surgery. Removal of coils may also increase the chance for poor outcome. Chance of poor outcome increased also with intraoperative aneurysm rupture, size of the aneurysm and posterior circulation location. Good clinical outcome, three months after surgery, was achieved in 71 patients (88%); four patients were severely disabled, and six patients died (three of them due to poor clinical condition). Complete microsurgical occlusion of the residual previously coiled aneurysm is a high-risk procedure in large and giant aneurysms, and these patients should be referred to a dedicated neurovascular center to minimize surgical complications. Bypass procedures may be the best option for demanding growing lesions, especially those in posterior circulation.

Posterior fossa extradural haematomas.

BACKGROUND: Posttraumatic epidural haematoma (EDH) of the temporal region is the most common site of supratentorial extradural bleeding; other locations are considered atypical. We reviewed 24 patients with EDH located in the posterior cranial fossa (PFEDH) treated at two neurosurgical centres between January 2000 and November 2006. MATERIAL AND METHODS: In the retrospective study we analysed gender and age distribution, type of injury, clinical presentation, Glasgow Coma Scale (GCS) score on admission, radiological images, interval between trauma and surgery, and outcome. RESULTS: 24 patients with PFEDH constituted 11.5% of 209 surgically treated individuals with EDH. The best outcomes were obtained by patients with GCS scores of 15-14 on admission. Patients in the fourth to seventh decade of life had less favourable outcomes than younger ones. More than half of the patients with PFEDH had associated intradural lesions. Only patients with concomitant brain contusion had a more favourable recovery. The 3 worst levels on the Glasgow Outcome Scale (GOS) were observed in patients suffering from subdural or intracerebral haematoma, or both, associated with the PFEDHs. The majority of patients with concurrent lesions and supratentorial extension of the haemorrhage were in the subgroup undergoing craniotomy between 24 and 72 h after injury. Patients treated in this time interval also had the most unfavourable outcomes. A classical lucid interval was observed only in one patient. The mortality rate in the series was 4.2%. CONCLUSION: The most significant factors influencing outcome in our patients were GCS on admission, age, and associated intradural lesions.

A massive binary black-hole system in OJ 287 and a test of general relativity.

Tests of Einstein's general theory of relativity have mostly been carried out in weak gravitational fields where the space-time curvature effects are first-order deviations from Newton's theory. Binary pulsars provide a means of probing the strong gravitational field around a neutron star, but strong-field effects may be best tested in systems containing black holes. Here we report such a test in a close binary system of two candidate black holes in the quasar OJ 287. This quasar shows quasi-periodic optical outbursts at 12-year intervals, with two outburst peaks per interval. The latest outburst occurred in September 2007, within a day of the time predicted by the binary black-hole model and general relativity. The observations confirm the binary nature of the system and also provide evidence for the loss of orbital energy in agreement (within 10 per cent) with the emission of gravitational waves from the system. In the absence of gravitational wave emission the outburst would have happened 20 days later.

Citalopram controls phobic symptoms in patients with panic disorder: randomized controlled trial.

OBJECTIVE: To examine the effects of long-term treatment with citalopram or clomipramine on subjective phobic symptoms in patients with panic disorder. DESIGN: Double-blind, parallel-group, five-arm study. PATIENTS: Patients aged 18 to 65 years with panic disorder (DMS-III-R diagnosis) and with no major depressive symptoms. INTERVENTIONS: Four hundred and seventy-five patients were randomized to 8 weeks of treatment with either citalopram (10 to 15 mg per day; 20 to 30 mg per day; or 40 to 60 mg per day), clomipramine (60 to 90 mg per day) or placebo. Two hundred and seventy-nine patients continued treatment after the 8-week acute phase. OUTCOME MEASURES: Phobic symptoms were assessed using the Phobia Scale and the Symptom Checklist's (SCL-90) phobia-related factors. RESULTS: At all dosages, citalopram was more efficacious than placebo, with 20 to 30 mg generally being the most effective dosage. Citalopram (20 to 30 mg) generally decreased phobic symptoms significantly more than placebo after Month 3. Interpersonal sensitivity decreased when measured on the respective SCL-90 sub-scale. Alleviation of phobic symptoms generally continued to increase towards the end of the treatment. The effect of clomipramine was not as consistent. CONCLUSIONS: All active treatment groups, especially the group receiving 20 to 30 mg per day of citalopram, effectively controlled phobic symptoms in patients with panic disorder. Long-term treatment with citalopram further decreased phobic symptoms.

A controlled, prospective, 1-year trial of citalopram in the treatment of panic disorder.

BACKGROUND: The objective of this study was to evaluate the efficacy and tolerability of citalopram in the long-term treatment of adult outpatients with panic disorder with or without agoraphobia. METHOD: Patients in this double-blind, parallel-group trial were assigned to 1 of 3 fixed dosage ranges of citalopram (10 or 15 mg/day, 20 or 30 mg/day, or 40 or 60 mg/day), 1 dosage range of clomipramine (60 or 90 mg/day), or placebo. After the completed 8-week acute treatment period, the eligible patients could continue the treatment for up to 1 year. Of the 475 patients who were randomly assigned for the short-term trial, 279 agreed to continue double-blind treatment at their assigned doses. The primary efficacy measure used was the Clinical Anxiety Scale panic attack item, and the response was defined as no panic attacks (score of 0 or 1). The other key measures used were the Physician's Global Improvement Scale, the Patient's Global Improvement Scale, and the Hamilton Rating Scale for Anxiety (HAM-A). RESULTS: In all drug-treated groups, except the group receiving the lowest citalopram dose, the treatment outcome was generally better than with placebo. As determined by a life table analysis of response, the probability of response during the 12 months was significantly greater with all treatment regimens than with placebo (p < .05), with citalopram 20 or 30 mg/day demonstrating the best response. Panic attacks tended to disappear in all patients remaining in the study until the end of follow-up. Analysis of the difference in the number of patients in different treatment groups remaining in the study (perhaps the best measure of long-term efficacy) also demonstrated that the patients treated with citalopram in dosage ranges of 20 or 30 mg/day and 40 or 60 mg/day had better response than placebo-treated patients (p < .0002 and p < .004, respectively). HAM-A and Global Improvement Scale scores also showed that patients treated with active drug showed greater improvement than placebo-treated patients. All treatment groups showed no new or exceptional adverse event clusters. CONCLUSION: Citalopram in the dosage range of 20 to 60 mg/day is effective, well tolerated, and safe in the long-term treatment of patients who have panic disorder.

Smoking and cognitive deficits in schizophrenia: a pilot study.

The cross-sectional study assessed the associations among smoking status, number of cigarettes smoked per day, and psychiatric symptoms in 88 chronic schizophrenic outpatients with a stable psychic condition. Among the 49 smokers, the number of cigarettes smoked per day was associated with the severity of cognitive symptoms of the Positive and Negative Syndrome Scale. The authors suggest that smoking may alleviate cognitive deficits in schizophrenia by increasing dopaminergic neurotransmission in the prefrontal areas of the brain.

Effect of smoking on neuroleptics in schizophrenia.

OBJECTIVE: The effect of smoking on daily doses and plasma levels of neuroleptics prescribed for schizophrenic patients was studied. METHODS: 90 outpatients with schizophrenic disorder (DSM-III-R) who were on a stable regimen of psychotropic medication and showed a stable clinical state were included in a double-blind placebo-controlled trial. Data were collected and blood tests taken at the baseline interview. The plasma levels were obtained for 52 patients. RESULTS: Daily neuroleptic doses converted to chlorpromazine equivalents correlated significantly (r = 0.436) with the plasma levels of their unmetabolised fractions. The neuroleptic doses increased with age in smokers, while in nonsmokers they decreased. Neither sex, age nor smoking had a significant association with the neuroleptic plasma levels. CONCLUSIONS: Smoking seems to lead to increased neuroleptic dosages in postmenopausal schizophrenics by increasing hepatic metabolism and renal excretion of the drugs and possibly enhancing dopamine release. It is also possible that older smoking patients form a selected group of heavy smoker and they, therefore, need exceptionally high neuroleptic doses.

Citalopram as an adjuvant in schizophrenia: further evidence for a serotonergic dimension in schizophrenia.

There is increasing evidence suggesting that symptoms of depression and anxiety may also be associated with serotonergic dysfunction in schizophrenic patients. The effect of the adjuvant selective serotonin reuptake inhibitor citalopram was assessed regarding the symptom dimensions of schizophrenia measured with the Positive and Negative Syndrome Scale (PANSS) and with the Hamilton Rating Scale for Depression (HRSD). Citalopram alleviated symptoms of the depression/anxiety dimension of the PANSS, but not the symptoms of the four other PANSS domains or depressive symptoms measured with the HRSD. The results support the hypothesis of a serotonergic dimension in schizophrenia.

Citalopram causes no significant alterations in plasma neuroleptic levels in schizophrenic patients.

Steady-state plasma concentrations of commonly used neuroleptic drugs were measured in 90 schizophrenic patients before and after adding placebo or citalopram (40 mg/day) to their treatment regimen. Plasma concentrations of citalopram and its main metabolite, desmethylcitalopram, were also measured. In addition, patients with exceptionally high neuroleptic levels or an increase in adverse effects during the 12-week study period were evaluated for their debrisoquine/sparteine hydroxylase (CYP2D6) genotype, an enzyme responsible for oxidative metabolism of several neuroleptics and selective serotonin re-uptake inhibitors. There were no significant changes in plasma concentrations of haloperidol, chlorpromazine, zuclopenthixol, levomepromazine, thioridazine or perphenazine during the study. Plasma concentrations of citalopram and desmethylcitalopram were well within the levels reported previously with monotherapy, and remained stable throughout the study. None of the 15 patients analysed for the CYP2D6 genotype was a poor metabolizer. It is concluded that clinically important pharmacokinetic drug interactions do not play a crucial role when citalopram is used as an augmentation therapy in neuroleptic-treated schizophrenic patients.

Citalopram as an adjuvant in chronic schizophrenia: a double-blind placebo-controlled study.

The effects of citalopram--the most selective serotonin reuptake inhibitor on the market--on psychopathological symptoms were studied in chronic schizophrenic patients on a stable regimen of neuroleptic medication. Outpatients suffering from schizophrenic disorder (DSM-III-R) with Positive and Negative Symptom Scale (PANSS) scores higher than 50 were included in a double-blind placebo-controlled add-on study. The daily dose of citalopram was 20 mg in the first week and 40 mg for the remaining period. A total of 90 patients (45 patients receiving citalopram and 45 receiving placebo) completed the 12-week trial. There were no changes in neuroleptic plasma levels during the trial. There was a significant decrease in total PANNS scores during the trial, although no statistically significant differences between the citalopram group and the placebo group were revealed. The number of responders in terms of severity of illness (CGI) was higher and the increase in subjective well-being (VAS) was greater in patients on citalopram than in those receiving placebo. There were no significant differences in the occurrence of side-effects. It is concluded that, in chronic schizophrenic out-patients, citalopram has no clear effect on the psychopathological symptoms; it may improve the general clinical condition, and it appears to increase the subjective well-being of these patients. Citalopram appears to be safe when used to treat schizophrenic patients who are receiving concomitant neuroleptic treatment.

Prediction of positive placebo response among chronic schizophrenic outpatients.

We undertook this study to determine whether predictors of positive placebo response in chronic schizophrenic outpatients could be identified. Twelve placebo responders and 33 placebo nonresponders who participated in a parallel-group, double-blind, 12-week clinical drug trial were compared. No significant differences between the groups were found with regard to 16 anamnestic and symptom variables. To investigate further which variables at baseline predicted positive placebo response, a stepwise linear regression model was created. Of the seven variables entered into the model, only high scores in the positive domain of the Positive and Negative Syndrome Scale (delusions, unusual thought content, grandiosity, and suspiciousness/persecution) at baseline predicted significantly positive placebo response (p = .0047). Because the onset of placebo response was gradual, the authors hypothesize that placebo response in chronic schizophrenia consists mainly of two ingredients: nonspecific psychotherapeutic effect caused by the several assessments carried out during the study, and regression toward the mean.

Citalopram, a selective serotonin reuptake inhibitor, in the treatment of aggression in schizophrenia.

The aim of this double-blind cross-over study was to investigate whether treatment with the selective serotonin reuptake inhibitor, citalopram reduces aggressiveness in chronically violent schizophrenic inpatients. Initially 19 patients were enrolled into this double-blind cross-over study in which the patients were treated for 24 weeks with placebo and 24 weeks with citalopram (20-60 mg/day) as a supplement to their previous neuroleptic medication. Fourteen patients completed the entire study, but sufficient data on 15 patients could be used in the end-point analysis of efficacy. Psychiatric assessments (Brief Psychiatric Rating Scale, Clinical Global Impression Scale for Severity of Illness, Social Dysfunction and Aggression Scale and the Global Aggression Scale) and side effects (UKU Side Effect Scale) were recorded at baseline and 4 times during both periods. Aggressive incidents (Staff Observation Aggression Scale) were recorded throughout the study. During citalopram treatment, the frequency of aggressive incidents was significantly lower and the mental state did not deteriorate. Patients either experienced no side effects or else side effects were equally mild during both periods.

Aspoxicillin versus piperacillin in severe abdominal infections--a comparative phase III study.

We compared aspoxicillin, a new broad-spectrum penicillin derivative, with piperacillin in severe abdominal infection. Aspoxicillin 4 g administered tds (n = 52) or piperacillin 4 g qds (n = 53) usually as monotherapy were randomly given to patients suffering from perforated appendicitis, acute cholecystitis, ulcer or colon perforation, or intra-abdominal abscess. Blood, tissue and exudate cultures were obtained when applicable for pathogen identification and susceptibility testing. The efficacy rates were similar in the two study groups. Of the 50 evaluable aspoxicillin patients 45 (90%) were considered as treatment responders compared with 48 patients out of 53 (91%) in the piperacillin group (NS). The 95% confidence interval for the efficacy difference was -12% to +11% thus showing no difference between the two drugs. Both drugs were generally well tolerated and no serious drug-related adverse events were noted. However, five patients died because of their illness and one patient had a fatal myocardial infarction. In conclusion, aspoxicillin 4 g tds was shown to be equal to piperacillin 4 g qds in severe abdominal infections.

Citalopram in patients with unsatisfactory response to neuroleptics: an open follow-up study.

There is clinical evidence that antidepressants have beneficial effects on certain symptom clusters of psychotic patients. Specific serotonin reuptake inhibitors like citalopram provide a new possibility to selectively influence brain neurotransmission. We studied the effects of citalopram (20-60 mg daily) in 36 psychotic or borderline patients receiving neuroleptic treatment without satisfactory response. Particular attention was paid to negative symptomatology, anxiety, and impulsiveness. 22 of the patients (65%) were assessed to react to citalopram treatment in a clinically significant manner. Initially, the responders tended to have higher scores in withdrawal-retardation, anxious-depression, and hostile-suspiciousness factors of the Brief Psychiatric Rating Scale (BPRS), with a lower degree of thinking disturbances. In the responder group, a significant decline in all symptom clusters was recorded. The mean decrease was 38% in Clinical Global Impression (CGI) and BPRS scales. The most prominent change (52%) was seen in hostile-suspiciousness factor of the BPRS inventory. In light of the positive results achieved in this open-label trial, controlled trials with patients not responding satisfactorily to neuroleptics are warranted.

Multiple-dose pharmacokinetic study with a slow-release carbamazepine preparation.

The pharmacokinetics, clinical efficacy and side effects of carbamazepine (CBZ) in the steady-state condition were studied using a slow-release preparation (SR), Neurotol Slow, and a conventional preparation (C), Tegretol. Eighteen adult epileptic patients under CBZ therapy were evaluated in this single-blind, randomized cross-over study. The previous daily CBZ dose was kept unchanged and divided into 2 daily doses during two 2 week study periods. At the end of each period blood samples were drawn at frequent intervals for 12 h after the administration of the morning CBZ dose. Serum concentrations of unchanged CBZ and its main metabolite, carbamazepine-10,11-epoxide (CBZE), were determined by HPLC. Peak concentrations of CBZ and CBZE were significantly lower, and the time-lapse before CBZ reached its peak was significantly longer during SR treatment. The fluctuations in serum CBZ and CBZE were significantly lower during SR treatment. There was no significant difference in bioavailability between the 2 preparations. The number of epileptic seizures was 31 during SR and 57 during C treatment. Side effects were more common during C treatment. The occurrence of dizziness was significantly lower with SR treatment than with C treatment. We conclude that greater stability in serum CBZ and CBZE concentrations can be obtained by using an SR of CBZ, without reducing the bioavailability of the drug.