IBD-PODCAST Spain: A Close Look at Current Daily Clinical Practice in IBD Management.

BACKGROUND: Crohn's disease (CD) and ulcerative colitis (UC) are inflammatory bowel diseases (IBD) that contributes in part to irreversible bowel damage and long-term complications, reduced quality of life, invalidity, and economic burden. Suboptimal control of IBD is associated with higher healthcare resource utilization (HCRU), impaired quality of life (QoL), and reduced work productivity. AIMS: The IBD-PODCAST study aimed to assess the proportion of IBD patients with suboptimal control and its associated impact. METHODS: IBD-PODCAST is a cross-sectional, multicenter study that aimed to characterize the CD and UC population with optimal or suboptimal control according to the STRIDE-II criteria and patient- and physician-reported measures. Here we present the results of the Spanish cohort (n = 396). RESULTS: A total of 104/196 (53.1%) CD and 83/200 (41.5%) UC patients were found to have suboptimal disease control. Long-term treatment targets according to STRIDE-II were applied in 172 (87.8%) CD and 181 (90.5%) UC patients. 125 of 172 (72.7%) CD and 74 of 181 (40.9%) UC patients were currently treated with targeted immunomodulators. Patients with CD and UC and suboptimal disease control showed impaired QoL, higher HCRU and direct costs, and also loss of work productivity compared to those with optimal control. CONCLUSION: Despite a high rate of targeted immunomodulator therapy, a substantial proportion of IBD patients show suboptimal disease control according to the STRIDE II criteria. Those patients with suboptimal disease control exhibit impaired QoL, less work productivity, and higher HCRU, suggesting that there is considerable need for better treatment approaches in IBD.

Evolution After Anti-TNF Discontinuation in Patients With Inflammatory Bowel Disease: A Multicenter Long-Term Follow-Up Study.

OBJECTIVES: The aims of this study were to assess the risk of relapse after discontinuation of anti-tumor necrosis factor (anti-TNF) drugs in patients with inflammatory bowel disease (IBD), to identify the factors associated with relapse, and to evaluate the overcome after retreatment with the same anti-TNF in those who relapsed. METHODS: This was a retrospective, observational, multicenter study. IBD patients who had been treated with anti-TNFs and in whom these drugs were discontinued after clinical remission was achieved were included. RESULTS: A total of 1,055 patients were included. The incidence rate of relapse was 19% and 17% per patient-year in Crohn's disease and ulcerative colitis patients, respectively. In both Crohn's disease and ulcerative colitis patients in deep remission, the incidence rate of relapse was 19% per patient-year. The treatment with adalimumab vs. infliximab (hazard ratio (HR)=1.29; 95% confidence interval (CI)=1.01-1.66), elective discontinuation of anti-TNFs (HR=1.90; 95% CI=1.07-3.37) or discontinuation because of adverse events (HR=2.33; 95% CI=1.27-2.02) vs. a top-down strategy, colonic localization (HR=1.51; 95% CI=1.13-2.02) vs. ileal, and stricturing behavior (HR=1.5; 95% CI=1.09-2.05) vs. inflammatory were associated with a higher risk of relapse in Crohn's disease patients, whereas treatment with immunomodulators after discontinuation (HR=0.67; 95% CI=0.51-0.87) and age (HR=0.98; 95% CI=0.97-0.99) were protective factors. None of the factors were predictive in ulcerative colitis patients. Retreatment of relapse with the same anti-TNF was effective (80% responded) and safe. CONCLUSIONS: The incidence rate of inflammatory bowel disease relapse after anti-TNF discontinuation is relevant. Some predictive factors of relapse after anti-TNF withdrawal have been identified. Retreatment with the same anti-TNF drug was effective and safe.

Health care costs of complex perianal fistula in Crohn's disease.

AIM: To evaluate the use of health care resources and the associated costs of complex perianal Crohn's disease (CD) from the National Health System perspective. METHODS: We conducted a multicenter, retrospective, observational study in which gastroenterologists from 11 hospitals in the Community of Madrid took part. Data was collected on the direct healthcare resources (pharmacological treatments, surgical procedures, laboratory/diagnostic tests, visits to specialists and emergency departments, and hospitalizations) consumed by 97 adult patients with complex perianal CD which was active at some point between January 1, 2005, and case history review. RESULTS: We recorded 527 treatments: 73.1% pharmacological (32.3% antibiotic, 20.5% immunomodulator, 20.3% biological) and 26.9% surgical. Mean annual global cost was €8,289/patient, 75.3% (€6,242) of which was accounted for by pharmacological treatments (€13.44 antibiotics; €1,136 immunomodulators; €5,093 biological agents), 12.4% (€1,027) by hospitalizations and surgery, 7.7% (€640) by medical visits, 4.2% (€350) by laboratory/diagnostic tests, and 0.4% (€30) by emergency department visits. CONCLUSIONS: Pharmacological therapies, and in particular biological agents, are the main cost driver in complex perianal CD; costs due to surgery and hospitalizations are much lower.

Evaluation of liver fibrosis by transient elastography (Fibroscan®) in patients with inflammatory bowel disease treated with methotrexate: a multicentric trial.

BACKGROUND: Methotrexate is an effective treatment for inflammatory bowel disease (IBD). However, long-term treatments have been associated with the development of liver fibrosis. FibroScan® is a noninvasive, safe, and effective technique to evaluate liver fibrosis. AIM: To evaluate the presence of significant liver fibrosis by transient elastography (FibroScan®) in IBD patients treated with methotrexate. METHODS: Cross-sectional study including IBD patients treated with methotrexate from different hospitals. Clinical and analytical data, duration of treatment, and cumulative dose of methotrexate were obtained. Liver stiffness was assessed by FibroScan®. The cutoff value for significant liver fibrosis (according to METAVIR) was F ≥ 2: 7.1 kPa. Results. In the study, 46 patients were included, 30 women (65%), with a mean age of 43 ± 10 years. 31 patients had Crohn's disease (67.4%), 13 ulcerative colitis (28.3%), and 2 indeterminate colitis (4.3%). The mean cumulative dose of methotrexate was 1242 ± 1349 mg, with a mean treatment duration of 21 ± 24 months. The mean value of liver stiffness was 4.7 ± 6.9 kPa. There were 35 patients (76.1%) with F01, 8 patients (17.4%) with F = 2, and 3 patients with F ≥ 3 (6.5%). There were no differences in liver stiffness depending on sex, age, type of IBD, or cumulative dose of methotrexate. CONCLUSIONS: (1) Development of advanced liver fibrosis in IBD patients treated with methotrexate is exceptional. (2) There were no differences in liver stiffness depending on the type of IBD or the cumulative dose of methotrexate. (3) FibroScan® may be potentially useful for evaluation and follow-up of liver fibrosis in methotrexate-treated patients.

Thiopurine methyl-transferase activity and azathioprine metabolite concentrations do not predict clinical outcome in thiopurine-treated inflammatory bowel disease patients.

BACKGROUND: Low thiopurine-methyl-transferase (TPMT) activity and high 6-thioguanine-nucleotide (6TGN) concentrations have been linked to therapeutic success in inflammatory bowel disease patients treated with thiopurines; however, this has not been implemented in clinical practice. AIM: To identify a therapeutic threshold value for TPMT or 6TGN concentrations, and their capability to predict treatment safety and efficacy. METHODS: Prospective multicentre study including steroid-resistant/dependent patients starting thiopurines. The TPMT activity was determined at inclusion (>5 U/mL required). Azathioprine metabolites [6TGN, 6-methyl-mercaptopurine ribonucleotides (6MMP), and 6TGN/6MMP and 6TGN/TPMT ratios] were periodically monitored during steroid tapering and after withdrawal for 6 months or until a new flare occurred. RESULTS: A total of 113 patients were analysed (62% clinical response). Areas under the receiver operating characteristic (ROC) curve (AUC) relating clinical response and metabolite levels at 2, 4 and 6 months after steroid withdrawal were less than 0.7. The AUCs relating final response and initial TPMT activity or metabolite concentrations at 2, 4, 8 and 16 weeks after starting thiopurines were less than 0.7. No cut-off point with worthwhile sensitivity/specificity was found. Eight (7%) patients developed thiopurine-related toxicity that could not be linked to TPMT activity or 6TGN levels. CONCLUSIONS: Our results do not support determination of TPMT activity or 6TGN concentrations to predict treatment outcome, and no useful serum metabolites threshold value to adjust the drug's dose was identified.

Identification of MNDA as a new marker for nodal marginal zone lymphoma.

Clinical and biological studies on nodal marginal zone lymphoma (NMZL) are hampered by the lack of specific diagnostic markers and the low reproducibility of this diagnosis. A comparative expression-profiling study has shown a set of markers to be differentially expressed in NMZL compared with follicular lymphoma (FL), including myeloid cell nuclear differentiation antigen (MNDA), a nuclear protein expressed by myeloid cells and a subset of B-cells. The aim of this study was to characterize the expression of MNDA in normal and reactive human tissue, and in a large series of non-Hodgkin's B-cell lymphomas, with particular emphasis on NMZL and FL. Our results showed that MNDA is expressed in normal tissue by a subset of the marginal zone B cells. They also showed MNDA expression in subgroups of chronic lymphocytic leukemia, mantle-cell lymphoma, and diffuse large B-cell lymphoma, but MNDA was especially expressed by lymphomas derived from the marginal zone, such as mucosa-associated lymphoid-tissue lymphoma, splenic marginal-zone lymphoma and NMZL. MNDA expression was rarely observed in FL, a characteristic that is of potential value in distinguishing between NMZL and FL. MNDA expression is thus a useful tool for the recognition of NMZL.

[Degree of public awareness regarding intensive care units (ICUs) and intensive care physicians in Castilla y León]. / Nivel de conocimiento sobre las unidades de cuidados intensivos (UCI) y los médicos intensivistas entre los ciudadanos de Castilla y León.

AIM: To determine degree of public awareness regarding the activities and health care professionals that comprise intensive care units (ICUs) in the autonomous community of Castilla y León. DESIGN: Questionaire in the form of a true-false test dealing with a) description of an ICU; b) description of ICU patients, and c) degrees and qualifications held by ICU physicians. LOCATION: Waiting rooms of outpatient clinics and ICUs of 9 hospitals in Castilla y León. SUBJECTS AND METHODS: During the period from 1 October 2003 to 29 February 2004, there were surveyed a group of those persons accompanying outpatients arriving for appointments (OP, n = 2,293), and a group comprised of relatives of ICU patients (ICU, n = 727) upon discharge from the ICU. RESULTS: The average age of those subjects surveyed was 45.6 years old. 62.1% were women and 52.8% had received education through secondary level or higher. Of the 1,354 analyzed OP questionnaires, 27.7%, 25.5% and 48.4% responded correctly to questions A, B and C, respectively. Of the 284 analyzed ICU questionnaires, 38.6%, 41.0%, and 63.5% responded correctly to questions A, B and C, respectively. Differences between results from the two surveyed groups were statistically significant, and the best results from the ICU group were found among those subjects whose family members had remained in ICU for 2 days or more. CONCLUSIONS: In the described scope, of the citizens of Castilla y León, 27.7% know as it is a ICU, 25.5% know what type of patients usually is entered there, and 48.4% recognize their doctors like ICU specialists specifically. These knowledge improve significantly after having some relative entered in ICU for more than 2 days.

Brachial-jugular expanded PTFE grafts for dialysis.

The objective of this study was to analyze the long-term outcome of 51 patients with brachial-jugular grafts for dialysis. Age, presence of diabetic nephropathy, complications of the angio-access, and therapeutic methods of treating complications were analyzed. All surgical procedures were performed under local anesthesia in an ambulatory surgical setting. The duration of angio-access was analyzed using the life-table method. Our results showed that brachial-jugular grafts can be performed under local anesthesia and in an ambulatory surgical setting. This procedure can be an alternative to complex intrathoracic procedures, Dacron cuff catheters, or lower limb grafts, in cases of stenosis or occlusion of the subclavian vein.

13C-urea breath test for the diagnosis of Helicobacter pylori infection before treatment: is citric acid necessary?

AIM: 13C-urea breath test is one of the best methods for the diagnosis of Helicobacter pylori infection. Although a citric acid solution is generally used prior to urea intake, the superiority of this strategy has not been sufficiently demonstrated. Thus, our aim was to compare 13C-urea breath test with and without citric acid solution, to evaluate whether 13C-urea breath test can also achieve favourable results when the test meal is omitted. METHODS: 13C-urea breath test with and without citric acid were compared prospectively in 53 subjects without prior Helicobacter pylori eradication therapy prescription. Basal samples and at 15', 30', and 45' after taking 100 mg of 13C-urea were obtained. The gold standard for Helicobacter pylori diagnosis was the 13C-urea breath test result with citric acid at 30', and "Delta Over Baseline" values >5 at that time were considered positive. RESULTS: The prevalence of Helicobacter pylori infection was 68%. Mean Delta Over Baseline values with citric acid at 15', 30' and 45' were: 29.6+/-39, 30.8+/-37 and 24.6+/-27; whereas respective values without citric acid were lower: 14.9+/-22, 12.2+/-17 and 10D+/-13 (p

Spanish family with Machado-Joseph disease: neurophysiological features and neuropathy study.

OBJECTIVES: We have carried out electrophysiological studies and sural nerve biopsy evaluation in a Spanish family with genetically proven Machado-Joseph disease (SCA3/MJD) phenotype III. PATIENTS AND METHODS: Two symptomatic and other two asymptomatic members of the family were clinically examined. Electrophysiological evaluation included multimodal evoked potentials, quantitative electromyography and nerve conduction studies, and central motor conduction time. We also report neuropathological findings in the sural nerve biopsy in the proband. RESULTS: Analysis of the SCA3/MJD CAG trinucleotide repeat at the ataxin 3 gene in the DNA of the proband and one of his daughters demonstrated an expanded allele of 63 CAG repeat units. Ataxic pursuit was primary disturbed in MJD, followed by gaze evoked nystagmus, hypermetric saccades and glissades. Limitation of vertical and horizontal gaze, impaired sinusoidal vestibulo-ocular reflex and vestibulo-ocular reflex-fixation-suppression, and active and passive optokinetic nistagmus loss appeared at later stages. Evoked potential studies showed multimodal abnormalities. Electrophysiological and sural nerve biopsy findings correspond well to a pattern of both anterior horn and root ganglion cell distal dominant degeneration. Central motor conduction time was normal in our patients up to advanced stages of the disease. CONCLUSIONS: Electrophysiological and neuropathological studies suggested widespread peripheral and central affection in MJD. Repeated application of electrophysiological techniques may prove useful for monitoring disease progress.

[Proximal vein by-pass in the treatment of venous stenosis in expanded polytetrafluoroethylene prosthesis for hemodialysis]. / By-pass a vena proximal para el tratamiento de estenosis venosas en prótesis de politetrafluoroetileno expandido para hemodiálisis.

OBJECTIVE: To show the long-term results of 97 politetraflouroethylene dialysis grafts submitted to a graft by-pass to treat graft-vein stenosis. MATERIALS AND METHODS: Venous stenoses were studied and diagnosed by means of fistulography in cases with fistula dysfunction or during surgery for graft thrombectomy. Both early and late complication rates were studied, as well as primary and secondary patency rates. RESULTS: Number of cases, 97. Mean age, 58 years (7-79). Diabetic nephropathy: 19.5%. Types of grafts in which stenoses developed: straight forearms 13; loop forearm 9; 6 mm upper arm 36; 6-8 mm upper arm 34; brachio-jugular 4; femoro-femoral 1. Overall follow-up time: 2,427 graft-months. Mean follow-up time: 21 +/- 5 months. Late complication rate: 0.30 episodes per graft-year of follow-up. Re-stenosis rate: 0.12 graft-year of follow-up. Primary cumulative patency rate: 70%, 62%, 51%, 45% at one, two, three and four years, respectively. Secondary cumulative patency rate: 87%, 79%, 74% and 71% at one, two, three and four years, respectively (p < 0.0016). No differences were observed between secondary patency observed after by-pass to treat dysfunction or thrombosis (p = 0.09259). DISCUSSION: In our experience, by-pass to proximal vein is associated with good results both at short and long term, probably because the intimal hyperplasia area is excluded and because by-pass is performed on an already dilated vein. The procedure can be performed under local anesthesia and in an outpatient basis between dialysis, with little discomfort for the patient.

Disability in multiple sclerosis. The role of transcranial magnetic stimulation.

Transcranial magnetic stimulation (TMS) was used to measure intensity threshold, conduction of the central motor pathways (CMCT) and amplitude of the motor evoked potentials (MEPs) in 50 patients with definite form of multiple sclerosis (MS), 31 females and 19 males, aged 15 to 58 years (mean 31.9 +/- 9.8). Abnormalities in at least one parameter after TMS have been found in 76% of the cases. Interside CMCT asymmetries increased the diagnostic yield to 86% of the patients. Three MS individuals with normal clinical examination have prolonged CMCT (silent lesions). There was significant correlation between CMCT and evolution of the disease, and with the degree of pyramidal signs. CMCT correlated with cerebral motor pathway, pons, and cervical cord lesions in MRI study. TMS is an easy and reliable method to quantify pyramidal and cerebellar dysfunction in MS and monitoring the evolution of the disease.

Gene dosage effect in one family with myoclonic epilepsy and ragged-red fibers (MERRF).

OBJECTIVES: We analyzed the percentage of mitochondrial DNA (mtDNA) heteroplasmy in blood samples of 13 individuals belonging to a three family generation of myoclonic epilepsy with ragged-red fibers (MERRF) and compared the 5 affected patients and the 8 unaffected relatives. MATERIAL AND METHODS: DNA was extracted from blood and muscle of the proband and from blood of 12 maternal relatives. A PCR restriction analysis method was used to detect the mutation. RESULTS: The proband had the complete MERRF phenotype. The phenotype in three other individuals in the maternal lineage was consistent with the MERRF syndrome. The remaining were asymptomatic. The np 8344 mutation was observed in muscle and blood of the proband, and in blood from every one of 12 maternal relatives, ranging from 44% to 83% of mutated genomes. Symptomatic individuals had higher levels (P < 0.001) of mutated mtDNA than asymptomatic maternal relatives. However, high proportions of mutant genomes (up to 63%) were found in asymptomatic relatives. CONCLUSIONS: Although there seems to be a gene dosage effect in MERRF, we found no absolute relationship between the relative proportion of mutant genomes in blood and clinical severity. Factors other than gene dosage in blood may account for the differences in clinical phenotype.

Peroneal arteriovenous fistula as a complication of above-knee femoropopliteal polytetrafluorethylene graft thrombectomy with the Fogarty catheter.

The Fogarty catheter is an invaluable tool in the surgical practice of a vascular surgeon. Arteriovenous fistula is an unusual but potentially dangerous complication of its use. We present the case of a man who suffered a peroneal arteriovenous fistula as a result of an above-knee femoropopliteal polytetrafluorethylene graft thrombectomy. As the fistula compromised the viability of the extremity, surgical correction was warranted. It was performed without further complications to the patient. The few cases reported in the literature are reviewed. We conclude that this complication should be repaired as soon as it is detected.

Electro-oculogram in multiple system and late onset cerebellar atrophies.

The present investigation uses electrooculogram to evaluate multiple system atrophy (MSA) and late onset cerebellar atrophies (LOCAs), both idiopathic (ILOCA) and late onset autosomal dominant cerebellar ataxia (ADCA). Forty cases were clinically examined using scales for cerebellar, pyramidal, parkinsonian, mental status and neuroimaging quantitative evaluations. The patients were classified into three groups: olivopontocerebellar atrophy (OPCA), striatonigral degeneration (SND), Shy-Drager syndrome (SDS), and LOCA. We have used direct current electro-oculography in order to establish their validity in making the diagnosis. Cerebellar signs were significantly correlated with impaired VOR-fix gain and OKN, abnormalities of saccades, and reduced smooth pursuit gain (p < 0.05). Pons atrophy was significantly correlated with impaired VOR-fix gain (p < 0.01), abnormalities of saccades (p < 0.01), and reduced smooth pursuit gain (p < 0.05). Cerebellar hemisphere atrophy was significantly correlated only with impaired VOR-fix gain (p < 0.05), and medulla oblongata atrophy only with abnormalities of saccades (p < 0.05). Gaze-evoked nystagmus was found in 42.8% of patients with OPCA, and only in 14.2% with SND, but was not found in LOCA patients (t test, p < 0.05). In patients with OPCA, the combination of gaze-evoked nystagmus, abnormalities of sinusoidal VOR and reduced OKN gain measurements was very frequent, while infrequent in both LOCA (Fisher's exact test, p < 0.05) and SND subjects (p < 0.01). SDS also showed abnormalities of the oculomotor system.

Multimodal evoked potentials in multiple system and late onset cerebellar atrophies.

Forty subjects were clinically examined using scales for cerebellar, pyramidal, parkinsonian, and mental status and by quantitative evaluation of neuroimages. The patients were classified into two groups: cerebellar-plus and "pure" cerebellar syndromes. Patients with "pure" cerebellar syndrome were diagnosed as autosomal dominant cerebellar ataxia III (ADCA III) or "pure idiopathic" late-onset cerebellar ataxia (ILOCA) in this series. Patients with cerebellar-plus syndrome were diagnosed as multiple system atrophy (MSA), subclassified as either ILOCA-plus, ADCA I, ADCA II or autosomal recessive LOCA. We have used visual (VEP), brainstem auditory (BAEP) and somatosensory (SEP) evoked potentials in order to establish their diagnostic validity. Cerebellar-plus syndrome and "pure" cerebellar syndrome showed overlapping VEP, BAEP and SEP abnormalities. VEP P100 latency, however, shows a certain ability to differentiate between the two groups (p = 0.08) and appears useful in distinguishing between sporadic cerebellar-plus syndromes (MSA or ILOCA-plus) and "pure" cerebellar syndromes (p < 0.02). The incidence of prolonged N9-N13 latency was significantly higher in the latter subgroup (p < 0.04) as well. Within cerebellar-plus syndromes, VEP, BAEP and SEP abnormalities were more frequent in inherited cases (ADCA I and II, along with autosomal recessive LOCA) than in sporadic ones. The most apparent differences were a higher incidence of abnormal BAEPs at brainstem level (p < 0.002), and of both peripheral and possible central SEP impairment in hereditary cerebellar-plus syndrome than in sporadic cerebellar-plus syndrome (p < 0.03). EP investigation is useful to a certain extent in differentiating between some variants of LOCA.

Cerebrotendinous xanthomatosis diagnosed after traumatic subdural haematoma.

We report the case of a 34-year old man, who, after presenting with subacute traumatic subdural haematoma, was diagnosed as CTX. He presented a ten year history of progressive deterioration of cognitive functions, unsteadiness of gait and surgery for bilateral cataracts at age 21. Cholestanol level in serum was 120.7 mmol/liter, and cholestanol/cholesterol ratio 2.52%. Bile alcohols in urine were 23, 25-pentol: 2.2665 mg/mmol creatinine, 24, 25-pentol: 1.3226 mg/mmol creatinine, and 27-nor-24, 25-pentol: 0.7363 mg/mmol creatinine. Electrophysiological study was consistent with a mixed demyelinating and axonal neuropathy. The assessment of autonomic nervous system (ANS) showed a postganglionic cholinergic failure accompanying somatic peripheral neuropathy. Brain-stem auditory evoked potentials (BAEPs) demonstrated markedly low amplitude and poorly defined waves, and almost symmetrical peak V and I to V interpeak latency (IPL) slight delays. Two nodular, bilateral, symmetrical lesions, strongly suggestive of calcifications, in the cerebellar white matter on CT and MRI were noted. On T2-weighted images diffuse high signal lesions were found in the cerebellar white matter, and multiple, hyperintense cerebral foci of demyelination or gliosis. MRI study of the Achilles tendon showed neither enlargement of the tendon, nor areas of lipid deposits. After ten months of treatment with chenodeoxycholic acid (CDCA) (750 mg/d) the clinical course was unaffected and the neurophysiological measures, CT and MRI remained unchanged.

Can nimodipine prevent ischaemic reperfusion injury in the rat brain?

Reperfusion injury is a pathophysiological entity distinct from the primary ischaemic injury; the oxygen arriving with blood recirculation, although necessary for alleviating the ischaemic status, may be harmful and provoke additional injury in the already damaged tissue. This study aims to analyse whether nimodipine reduces cerebral dysfunction after transient global cerebral ischaemia, using our previously described experimental model, which permits the impregnation of cerebral tissue during the periods of ischaemia and reperfusion. Some aspects of this study contribute to our understanding of the reperfusion injury concept. Three groups of rats were used. Animals in Group 1 (n = 13) served as normal controls for neurophysiological recordings. Rats in Groups 2 (n = 7) and 3 (n = 7) were subjected to global cerebral ischaemia and either isotonic saline (Group 2) or nimodipine solution (Group 3; 40 micrograms/kg) was intra-arterially injected through the external carotid artery during ischaemia and reperfusion and distributed to the circle of Willis. Seventy-two hours after global cerebral ischaemia somatosensory evoked potentials were evaluated and P1 wave latency was used to compare the three groups of animals. The peak onset of this wave was 8.13 +/- 1.5 msec, 18.63 +/- 3.1 msec and 13.17 +/- 2 msec for Groups 1, 2 and 3 respectively. P1 latency was significantly higher in Group 2 than in Groups 1 and 3 (p < 0.01). Histopathological findings showed that the level of injury in the hippocampus and striatum in Group 3 was more limited than in Group 2, although no statistical significance could be found.(ABSTRACT TRUNCATED AT 250 WORDS)

Prevention of cerebral ischaemic reperfusion injury by intra-arterial administration of superoxide dismutase in the rat.

An experimental test was performed to determine whether superoxide dismutase, an oxygen-free radical scavenger, reduces neurological dysfunction after transient global cerebral ischaemia. Three groups of 13 rats each were used. Group 1 served as normal controls. Groups 2 and 3 were subjected to transient global cerebral ischaemia. Before ischaemia, the right carotid bifurcation was isolated and the right external carotid artery was retrogradely cannulated, with the catheter tip positioned near the origin of the internal carotid artery. Once global cerebral ischaemia was complete, either isotonic saline (group 2) or superoxide dismutase solution (group 3) was injected through the above-mentioned catheter, before, during and after reperfusion. Consequently, the injected solutions were distributed through the circle of Willis to all of the ischaemic brain tissue. Somatosensory evoked potentials were registered in the three groups of animals and were used as a measure of neuronal function. In control animals (group 1) mean P1 latency was 8.1 msec and while the mean P1 latency was 11.9 msec in the isotonic saline treated animals (group 2), it was reduced to 8.8 msec in rats treated with the superoxide dismutase solution (group 3). P1 latency was significantly higher in group 2 than in groups 1 and 3 (P less than 0.001). As evaluated by somatosensory evoked potentials, we have concluded that the intra-arterial injection of superoxide dismutase to the ischaemic tissue improves neuronal function in rats subjected to transient global cerebral ischaemia.