Angiographic vasospasm and release of platelet thromboxane after subarachnoid hemorrhage

We studied adenosine diphosphate-induced platelet aggregation and the associated release of thromboxane B2 in 49 patients with subarachnoid hemorrhage in relation to angiographic vasospasm. Postoperative cerebral angiography was performed less than or equal to 3 (median 1) days after surgery for an aneurysm 5-14 days after subarachnoid hemorrhage. Correspondingly, one sample from each patient was taken within 24 hours either before or after angiography. The occurrence of severe as well as diffuse, moderate, or severe angiographic vasospasm was associated with the presence of delayed cerebral ischemia (p less than 0.05). Patients with diffuse angiographic vasospasm had significantly higher (p less than 0.05) values for thromboxane B2 release than the others, even after adjustment by the clinical grades on admission and before surgery, the timing of surgery, the time from subarachnoid hemorrhage to angiography and blood sampling, and nimodipine therapy. Severe and diffuse angiographic vasospasm were also associated with poor outcome at 1 year (p less than 0.05). Our results suggest that augmented release of platelet thromboxane may be involved in the pathogenesis of vasospasm in large cerebral arteries.     

Altered enzyme activities of xenobiotic biotransformation in kidneys after subchronic administration of 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX) to rats

Activities of the xenobiotic metabolizing enzymes were measured in the liver, kidney, duodenum and lung microsomes and cytosol fractions of Wistar rats after subchronic administration of 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX), a potent bacterial mutagen in chlorinated drinking water. MX was administered by gavage at the dose level of 30 mg/kg for 18 weeks (low dose), or at the dose level which was raised gradually from 45 mg/kg for 7 weeks via 60 mg/kg for 2 weeks to a clearly toxic dose of 75 mg/kg for 5 weeks (high dose). Microsomal and cytosolic preparations were made and the activities of 7-ethoxyresorufin-O-deethylase (EROD), pentoxyresorufin-O-dealkylase (PROD), NADPH-cytochrome-c-reductase, UDP-glucuronosyltransferase (UDPGT) and glutathione-S-transferase (GST) were measured. Kidneys were affected most. A dose-dependent decrease was observed in EROD (90% in males, 80% in females at the high dose) and in PROD (58% in females, at the high dose) in kidneys. An increase was, however, detected in kidney NADPH-cytochrome-c-reductase (66% in females at high dose), UDPGT (89% in males and 97% in females at high dose) and GST activities (56% in males and 50% in females at high dose). MX caused only a few changes in the enzyme activities of the liver. The EROD activity was decreased 25% to 37%, both in the livers of males and females, but the total content of P450s was not altered. Hepatic GST activity was elevated in females in a dose-dependent manner (31% and 44%). GST activity was elevated in duodenum in females (59%) at the high dose. There were no marked changes in the enzyme activities in the lungs. MX was a weak inhibitor of EROD activity both in the liver and kidney microsomes in vitro, decreasing the EROD activity by 53% and 43%, respectively at the concentration of 0.9 mM. The results indicate that MX decreases the activity of phase I metabolism enzymes, but induces phase II conjugation enzyme activities, particularly in kidneys in vivo. It is possible that these changes contribute to metabolism of MX in kidneys and renders them susceptible to MX in the course of repeated exposure.     

Effect of linoleic acid, linoleic acid anilide, and arachidonic acid on the expression of adhesion molecules on human neutrophils

The effects of linoleic acid, linoleic acid anilide, and arachidonic acid on the expression of CD11b/CD18, CD11c/CD18 integrins and l-selectin on human neutrophils were studied by flow cytometry in a whole blood assay. None of these compounds had any effect on the basal expression of CD11b, CD11c, or l-selectin in the concentration range of 20–100 μM. However, linoleic acid at a concentration of 1000 μM slightly up-regulated CD11b and CD11c by a factor of 2.1 and 1.7, respectively. Linoleic acid, linoleic acid anilide, and arachidonic acid did not affect the formyl-methionyl-leucyl-phenylalanine induced up-regulation of CD11b or CD11c. However, linoleic acid and linoleic acid anilide slightly inhibited the phorbol myristate acetate (PMA)-induced expression of CD11b, which was decreased by 27 and 21% at concentrations of 100 and 1000 μM, respectively. Likewise, arachidonic acid at 40 μM inhibited the PMA-induced expression of CD11b by 19%. Our results suggest that linoleic acid, linoleic acid anilide, and arachidonic acid do not dramatically affect the expression of leukocyte adhesion molecules in a whole blood assay. Received: 17 February 1997  / Accepted: 5 May 1997     

Molecular epidemiology of two international sprout-borne Salmonella outbreaks.

Sprout-borne Salmonella outbreaks in Finland have increased during the last 10 years. The latest two were caused by Salmonella enterica serovar Bovismorbificans (antigenic structure 6,8:r:1,5) in 1994 and S. enterica serovar Stanley (4,5, 12:d:1,2) in 1995. In this study, the restriction fragment length polymorphism of genomic DNA after pulsed-field gel electrophoresis (PFGE) and antimicrobial resistance profiles of the outbreak and nonoutbreak strains were compared. In each separate outbreak, the PFGE patterns of the outbreak strains (40 strains of S. enterica serovar Bovismorbificans and 28 strains of S. enterica serovar Stanley) after digestion of genomic DNA with restriction enzyme XbaI were indistinguishable from each other but differed clearly from those of the nonoutbreak strains (26 strains of S. enterica serovar Bovismorbificans and 40 strains of S. enterica serovar Stanley). The restriction enzyme XhoI did not differentiate the outbreak and nonoutbreak strains. The S. enterica serovar Stanley strains associated with the outbreak also had a unique antimicrobial resistance pattern, whereas all S. enterica serovar Bovismorbificans strains, both outbreak and nonoutbreak strains, were sensitive to all antimicrobial agents tested. Thus, the molecular typing confirmed that the S. enterica serovar Bovismorbificans outbreak isolates from humans and sprout salad were identical and strongly supported the epidemiological finding that S. enterica serovar Stanley outbreak isolates also originated from contaminated alfalfa seeds. It also confirmed that the sources of similar outbreaks in Sweden in 1994 caused by S. enterica serovar Bovismorbificans and in the United States in 1995 caused by S. enterica serovar Stanley and the source of the Finnish outbreaks were common.     

Cholinergic basal forebrain structures are involved in the mediation of the arousal effect of noradrenaline

Cholinergic basal forebrain structures are implicated in cortical arousal and regulation of the sleep–wake cycle. Cholinergic neurones are innervated by noradrenergic terminals, noradrenaline excites them via alpha‐1 receptors and microinjection of noradrenaline into the basal forebrain enhances wakefulness. However, it is not known to what extent the cholinergic versus non‐cholinergic basal forebrain projection neurones contribute to the arousing effects of noradrenaline. To elucidate the roles of cholinergic basal forebrain structures we administered methoxamine, an alpha‐1‐adrenergic agonist into the basal forebrain, in intact animals and again after selective destruction of the basal forebrain cholinergic cells by 192 IgG‐saporin. In eight male Han–Wistar rats implanted with electroencephalogram/electromyogram electrodes, a microdialysis probe targeted into the basal forebrain was perfused with artificial cerebrospinal fluid for 6 h on a baseline day, and with cerebrospinal fluid in the first and with methoxamine in the second 3‐h period of the subsequent day. The sleep–wake activity was recorded for 24 h on both days. Saporin was then injected into the basal forebrain and 2 weeks later the same experimental schedule (with cerebrospinal fluid and methoxamine) was repeated. In the intact animals, methoxamine exhibited a robust arousing effect and non‐rapid eye movement (NREM) and REM sleep was suppressed. Lesioning of the basal forebrain cholinergic neurones abolished almost completely the NREM sleep‐suppressing effect of methoxamine, whereas the REM sleep‐suppressing effect remained intact. Thus, the basal forebrain cholinergic neurones mediate, at least in part, cortical arousal and non‐REM sleep‐suppression, but they are not involved in the REM sleep‐suppressing effects of noradrenaline.     

Occurrence of desmoid tumours in familial adenomatous polyposis and results of treatment

Desmoids are of major concern in patients with familial adenomatous polyposis (FAP) besides the cancer risk. We estimated the risk for desmoid tumours and the results of their treatment in the Finnish Polyposis Registry. The analysis included 202 FAP patients, of whom 169 had undergone colectomy. Desmoids were observed in 29 cases: 15 in the mesentery, 10 in the abdominal wall and 4 in other sites. There were 12 male and 17 female patients with a mean age of 28.2 years (range 7 months to 59 years). The cumulative life-time risk was 21%; 1.5, 3.0, 8.9, 16 and 18% at ages of 10, 20, 30, 40 and 50 years, respectively. The risk of postcolectomy desmoids was 17% after ileorectal anastomosis and 12% after proctocolectomy. There were no deaths due to desmoids. One abdominal scar desmoid disappeared spontaneously and all the other abdominal wall desmoids could be excised without complications, but recurrence occurred in five (45%) cases. Excision was possible in only nine mesenteric desmoids (56%); in these cases recurrence was less common (two cases, 22%) but two others had lifethreatening compli-cations (bleeding, short bowel). We conclude that the desmoid problem concerns more than 20% of all FAP patients in long-term. Despite high recurrence rates and surgical hazards surgery remains a useful option for most desmoid tumours in FAP patients considering that other treatments are often ineffective or hazardous as well.

---

Résumé. Outre le risque de cancer, les tumeurs desmo?des constituent un problème majeur chez les patients porteurs d'une polypose adénomateuse familiale (FAP). Nous avons évalué le risque de tumeurs desmo?des et le résultat de leur traitement sur la base du registre finlandais des polyposes. L'analyse inclut 202 patients porteurs d'une polypose familiale dont 69 ont subi une colectomie. Des tumeurs desmo?des ont été observées dans 29 cas: 15 fois dans le mésentère, 10 fois au niveau de la paroi abdominale et 4 fois dans d'autres sites. Il s'agit de 12 patients de sexe masculin et 10 de sexe féminin avec une moyenne d'age de 28.2 ans (7 à 59 ans). Le risque cumulatif est de 21%; 1.5, 3.0, 8.9, 16 et 18% à respectivement 10, 20, 30, 40 et 50 ans. Le risque d'une tumeur desmo?de après colectomie est de 17% en cas d'anastomose iléo-rectale et de 12% aprés procto-colectomie. Aucun décès ne résulte de la lésion desmo?de. Une cicatrice abdominale desmo?de a disparu spontanément et toutes les autres tumeurs desmo?des de la paroi abdominale ont pu être excisées sans complications mais avec une récidive dans 5 cas (45%). Une excision n'a été possible que chez 9 patients porteurs de tumeurs desmo?des mésentériques (56%); le risque de récidive dans ces cas était moindre (2 cas, 22%) mais 2 complications entra?nant des risques vitaux se sont produites (hémorragie, intestin court). Nous concluons de cette étude que le risque d'une tumeur desmo?de concerne plus de 20% de tous les patients porteurs de polypose adénomateuse familiale à long terme. Malgré un taux de récidive élevé et malgré les risques chirurgicaux, le traitement chirurgical demeure l'option de choix pour le traitement des traitements desmo?des survenant chez des patients porteurs de polypose familiale étant donné que tous les autres traitements sont hasardeux et également inefficaces.

---

---

Accepted: 29 March 1996     

Health-related quality of life-testing the reliability of the MSQOL-54 instrument among MS patients

The purpose of the study was to assess the reliability of the specific multiple sclerosis quality of life (MSQOL-54) instrument, which contains 54 items measuring quality of life, among Finnish multiple sclerosis (MS) patients. Nursing professionals evaluated the clarity and comprehensibility of the translated instrument, after which it was pilot-tested. The data were collected through a questionnaire survey in the spring 2004. Persons diagnosed with MS in 1999-2001 filled in the questionnaire (n = 100). The response percentage was 81%. The structural validity of the MSQOL-54 instrument was evaluated with factor analysis and the generic 15D quality of life instrument. The internal consistency of the instrument was measured with Cronbach's alpha, correlations and item analysis. According to the results, the structural validity of MSQOL-54 was good, and factor analysis yielded a clear-cut factorial model. More than half of the correlations between the comparable items of the 15D and MSQOL-54 instruments were moderate or better. The internal consistency of MSQOL-54 can hence be considered quite good: Cronbach's alpha coefficients calculated for the factors and their items ranged within 0.33-0.89. The alpha coefficient calculated for the whole instrument was 0.84. The internal consistency of MSQOL-54 was further confirmed by the results of an item analysis, which showed the correlation coefficients between the items of the different dimensions to be good (0.31-0.81). On the basis of the test results, the MSQOL-54 instrument is fairly reliable and suitable for assessing the health-related quality of life of MS patients. The reliability of MSQOL-54 should be evaluated further by a longitudinal study design in the future.     

Periodic properties of the histaminergic system of the mouse brain

Brain histamine is involved in the regulation of the sleep–wake cycle and alertness. Despite the widespread use of the mouse as an experimental model, the periodic properties of major markers of the mouse histaminergic system have not been comprehensively characterized. We analysed the daily levels of histamine and its first metabolite, 1‐methylhistamine, in different brain structures of C57BL/6J and CBA/J mouse strains, and the mRNA level and activity of histidine decarboxylase and histamine‐N‐methyltransferase in C57BL/6J mice. In the C57BL/6J strain, histamine release, assessed by in vivo microdialysis, underwent prominent periodic changes. The main period was 24 h peaking during the activity period. Additional 8 h periods were also observed. The release was highly positively correlated with active wakefulness, as shown by electroencephalography. In both mouse strains, tissue histamine levels remained steady for 24 h in all structures except for the hypothalamus of CBA/J mice, where 24‐h periodicity was observed. Brain tissue 1‐methylhistamine levels in both strains reached their maxima in the periods of activity. The mRNA level of histidine decarboxylase in the tuberomamillary nucleus and the activities of histidine decarboxylase and histamine‐N‐methyltransferase in the striatum and cortex did not show a 24‐h rhythm, whereas in the hypothalamus the activities of both enzymes had a 12‐h periodicity. These results show that the activities of histamine‐metabolizing enzymes are not under simple direct circadian regulation. The complex and non‐uniform temporal patterns of the histaminergic system of the mouse brain suggest that histamine is strongly involved in the maintenance of active wakefulness.