Antithrombin reduces pulmonary hypertension during reperfusion after cardiopulmonary bypass in a pig

BACKGROUND: Antithrombin (AT) may alleviate many cardiopulmonary bypass (CPB) and ischemia-reperfusion (I/R)-related adverse effects. Using a porcine model of clinical cardiac surgery on CPB, we tested the effects of supplementary AT on myocardial and lung I/R injury. METHODS: Twenty pigs undergoing 60-min aortic clamping and 75-min normothermic perfusion were randomized in a blinded setting to receive an intravenous (i.v.) bolus of AT (250 IU/kg) (AT group, n = 10) or placebo (n = 10) 15 min before aortic declamping. An additional group of five animals received 500 IU/kg AT in an open-label setting (AT+). Thrombin-antithrombin complexes (TAT), activated clotting times (ACT), AT and myeloperoxidase (MPO) activities, troponin T, and several hemodynamic parameters were measured before CPB and after weaning from CPB up to 120 min after aortic declamping. After 120 min of reperfusion, myocardial and lung biopsies were taken for histological examination. RESULTS: AT effectively inhibited coagulation as assessed by ACT. In the AT and AT+ groups only, cardiac output (CO) and stroke volume (SV) showed a trend of post-ischemic recovery during the first 15 min after CPB. AT-attenuated reperfusion induced an increase in pulmonary arterial diastolic pressure (PAPD) but did not have significant effects on systemic or pulmonary vascular resistance. The effects of AT on SV, CO, and PAPD were fortified in the AT+ group. AT did not show effects on inflammatory changes in either myocardial or pulmonary tissue specimens. AT did not reduce post-ischemic troponin T release. CONCLUSION: Supplementary AT, in doses with significant anticoagulant effect, did not alleviate myocardial I/R injury in terms of histological inflammatory changes or post-ischemic troponin T release. Instead, however, AT-attenuated reperfusion induced an increase in pulmonary pressure after CPB. Mechanisms and clinical implications of these effects remain to be explored.     

Enrolment of 22,000 adolescent women to cancer registry follow-up for long-term human papillomavirus vaccine efficacy: guarding against guessing

Human papillomaviruses (HPVs, most notably types 16 and 18) cause cervical carcinoma, the second most common cancer among women. Vaccination of adolescents against HPV16/18 might prevent large proportion of cervical and other anogenital cancers. However, because of ethical reasons this cannot be proven by clinical studies. To determine the long-term vaccine efficacy (VE) of HPV16/18 virus-like-particle (VLP) vaccine against cervical carcinoma in situ (CIS+) and invasive cervical carcinoma, the following three population-based cohorts of adolescent women have been enrolled: (1) women vaccinated with the HPV vaccine; (2) women vaccinated with hepatitis A control vaccine; and (3) unvaccinated control women. These cohorts will be passively followed for cumulative incidence of CIS+ endpoints by population-based cancer registry. Overall 24,046 16- to 17-year-old adolescent women from 18 cities in Finland were invited between May 2004 and June 2005 to participate in a phase III trial with bivalent HPV16/18 VLP vaccine. A total of 58,996 18- to 19-year-old women were invited in May 2005 to participate as unvaccinated controls. Women who reported their willingness to participate in an HPV vaccination trial had they been 1-2 years younger were eligible. Cumulative incidence (CI) of CIS+ in our cohorts over 15 years is approximately 0.45%. VE of 70% against CIS+ with 80% power requires 3357-3189 HPV16/18 vaccine recipients, 3357-3189 other vaccine recipients, and 6714-9567 unvaccinated controls. We have now enrolled 2404 HPV16/18 vaccine recipients, 2404 hepatitis A-vaccine recipients, and 5130 unvaccinated controls. This enrolment in addition to our earlier enrolment in another phase III trial guarantees enough power so that by 2020 we can ultimately provide data on the efficacy of HPV16/18 vaccination against CIS+.     

Genital Chlamydia trachomatis infections in patients with cervical atypia.

Of 177 gynecologic outpatients with cervical dysplasia studied, 29 (16%) were found to excrete Chlamydia trachomatis from their urogenital tract. Sera collected from 93 of these patients were significantly more often positive for and showed higher levels of antichlamydial micro-complement fixation (CF) and immunofluorescence (IF) antibodies than sera obtained from the controls. However, when the sera were tested for anti-herpesvirus type II (HSV-II) and cytomegalovirus (CMV) antibodies, no difference between the cases and the controls were encountered.     

Day Length Associates with Activity Level in Children Living at 60 Degrees North

The associations between day length and activity, rest-activity rhythm, and psychiatric symptoms were studied. Sixty-six healthy children participated in the study during one year. They were monitored for 72 consecutive hours with belt-worn activity monitors (actigraphs) to obtain objective data on their activity levels during the day and night. In addition, the parents filled out the Child Behavior Checklists. It was found, that the mean total and day and night time activity levels were increased and the relative circadian amplitude blunted with the longer day length. It was concluded that day length was associated with activity level and rest-activity rhythm and this association may reflect the seasonal changes in these parameters.     

Poor sleep and psychiatric symptoms at school: an epidemiological study

The objective of this study was to evaluate associations between sleep problems and psychiatric symptoms at school. A random sample consisting of 5813 eight- to nine-year-old children was selected from ordinary schools. Both parents' and children's reports of sleep problems were taken into account. The psychiatric symptoms were addressed according to the teachers' reports (the Rutter Scale B). Children with severe sleep problems were more likely to have a psychiatric disturbance according to the Rutter B Scale (OR 2.45, 95 % CI 1.85–3.25). Logistic regression models showed that severe sleep problems were highly associated with emotional problems (OR 2.74, 95 % CI 1.84–4.13), school attendance problems (OR 2.53, 95 % OR 1.45–4.41), behavioural problems (OR 2.44, 95 % CI 1.59–3.75) and hyperactivity (OR 2.02, 95 % CI 1.30–3.13). Over 95 % of severe sleep problems were reported only by the children themselves. In conclusion, children with severe sleep problems have substantially more teacher-reported psychiatric symptoms than those with no or mild sleep complaints. In diagnosing sleep disorders, it is important to include children as informants because relevant information may be overlooked when only parents are questioned. Accepted: 20 August 2001     

Observer variability in the scoring of colpophotographs

Colposcopy and cervicography are accepted tools for assessing the cervix for an atypical transformation zone. We studied the validity of the colpophotograph as a measurement tool by determining the agreement of experienced colposcopists using colpophotographs of 50 women. Interobserver agreement was generally fair to good (kappa greater than or equal to 0.40) for the presence of the squamocolumnar junction and the area of ectopia but it was poor (kappa less than 0.40) for the area, border, and color characteristics of an atypical transformation zone. Intra-observer agreement was fair to good for the color characteristics of an atypical transformation zone, but it was poor for the area and border characteristics. We conclude that observer agreement studies should play a role in the validation of methods used in the visual diagnosis of cervical intraepithelial neoplasia. Considerable lack of agreement in reporting cytologic findings is a well-known problem, and lack of agreement might be an even bigger problem in reporting colposcopic findings.     

Serum CA 125 in acute pelvic inflammatory disease

Serum levels of CA 125 and other selected tumour markers were measured in 31 patients with proven pelvic inflammatory disease (PID). Ten (32%) of the patients had elevated CA 125, one (4%) had elevated CEA, and none had elevated CA 15-3, AFP or beta 2-microglobulin. Compared to patients with normal CA 125, patients with elevated CA 125 were older, more often users of intrauterine contraceptive devices, had longer duration of symptoms, higher erythrocyte sedimentation rates, and more often had an adnexal mass on pelvic examination. There was a correlation between CA 125 levels and the severity of adnexal inflammation as defined by laparoscopy. Isolation of specific micro-organisms from the upper genital tract was not associated with elevated CA 125. In most women serum levels of CA 125 decreased during treatment. PID should be considered as a major cause of positive CA 125 findings among young women.