Influence of bradykinin B1 and B2 receptors in the immune response triggered by renal ischemia–reperfusion injury

Bradykinin B1 receptors are exclusively expressed in inflamed tissues. For this reason, they have been related with the outcomes of several pathologies. Ischemia–reperfusion injury is caused by the activation of inflammatory and cytoprotective genes, such as macrophage chemoattractant protein-1 and heme oxygenase-1, respectively. This study was aimed to analyze the involvement of bradykinin B1 and B2 receptors (B1R and B2R) in tissue response after renal ischemia–reperfusion injury. For that, B1R (B1−/−), B2R (B2−/−) knockout animals and its control (wild-type mice, B1B2+/+) were subjected to renal bilateral ischemia, followed by 24, 48 and 120 h of reperfusion. At these time points, blood serum samples were collected for creatinine and urea dosages. Kidneys were harvested for histology and molecular analyses by real-time PCR. At 24 and 48 h of reperfusion, B1−/− group resulted in the lowest serum creatinine and urea levels, indicating less renal damage, which was proved by renal histology. Renal protection associated with B1−/− mice was also related with higher expression of HO-1 and lower expression of MCP-1. In conclusion, the absence of B1R had a protective role against inflammatory responses developed after renal ischemia–reperfusion injury.     

Carotid baroreflex function ceases during vasovagal syncope

Abstract. Despite the arterial baroreflex control of heart rate and blood pressure, vasovagal syncope is a common cause of loss of consciousness in people exposed to stimuli that reduce the central blood volume, such as head-up tilt. Carotid baroreflex function was evaluated using a rapid pulse train of neck pressure and neck suction in three conscious volunteers who developed a vasovagal episode during head-up tilt. The maximal gain of the carotid-heart rate and carotid-blood pressure baroreflex function curves were identified as measures of carotid baroreceptor responsiveness. When presyncopal symptoms developed, one further baroreflex assessment was obtained before the subjects were returned to the supine position. The bradycardia and hypotension exhibited during pre-syncope and syncope reflected a leftward and downward relocation of both the cardiac and vasomotor stimulusresponse curves. In addition, during the vasovagal syncope, baroreflex control was suppressed as blood pressure remained low during neck pressure stimuli. In conclusion, arterial baroreflex function ceases during vasovagal syncope.     

Danish version of the Oswestry disability index for patients with low back pain. Part 2: Sensitivity, specificity and clinically significant improvement in two low back pain populations

In studies evaluating the efficacy of clinical interventions, it is of paramount importance that the functional outcome measures are responsive to clinically relevant change. Knowledge thereof is in fact essential for the choice of instrument in clinical trials and for clinical decision-making. This article endeavours to investigate the sensitivity, specificity and clinically significant improvement (responsiveness) of the Danish version of the Oswestry disability index (ODI) in two back pain populations. Two hundred and thirty three patients with low back pain (LBP) and/or leg pain completed a questionnaire booklet at baseline and 8 weeks follow-up. Half of the patients were seen in the primary (PrS) and half in the secondary sectors (SeS) of the Danish Health Care System. The booklet contained the Danish version of the ODI, along with the Roland Morris Questionnaire, the LBP Rating Scale, the SF36 (physical function and bodily pain scales) and a global pain rating. At follow-up, a 7-point transition question (TQ) of patient perceived change and a numeric rating scale relating to the importance of the change were included. Responsiveness was operationalised using three strategies: change scores, standardised response means (SRM) and receiver operating characteristic (ROC) analyses. All methods revealed acceptable responsiveness of the ODI in the two patient populations which was comparable to the external instruments. SRM of the ODI change scores at 2 months follow-up was 1.0 for PrS patients and 0.3 for SeS (raw and percentage). A minimum clinically important change (MCID) from baseline score was established at 9 points (71%) for PrS patients and 8 points (27%) for SeS patients using ROC analyses. This was dependable on the baseline entry score with the MCID increasing with 5 points for every 10 points increase in the baseline score. We conclude that the Danish version of the ODI has comparable responsiveness to other commonly used functional status measures and is appropriate for use in low back pain patients receiving conservative care in both the primary and secondary sector.     

Academic Achievement of Children with Epilepsy

The academic achievement scores of 122 children with epilepsy were examined in relation to demographic and clinical seizure variables. As a group, these children were making less academic progress than expected for their age and IQ level. Academic deficiencies were greatest in arithmetic, followed by spelling, reading, comprehension, and word recognition. Results of the multiple regression analyses indicated a modest combined predictive significance of the demographic and clinical seizure variables for academic performance. In addition, the magnitude of these relationships varied by academic area. Among the individual variables examined the strongest correlates of academic performance were age of the child, age of seizure onset, lifetime total seizure frequency, and presence of multiple seizures (absence and tonic-clonic). These results are discussed in relation to developing an understanding of the factors which underlie academic vulnerability in children with epilepsy.     

Need for bilateral arthroplasty for coxarthrosis 1, 477 replacements in 1, 199 patients followed for 0-14 years

During the 10-year period 1981-1990, 1, 199 patients in the county of South Jutland, Denmark, had 1, 477 primary total hip arthroplasties (THA) performed because of primary arthrosis (OA).

The patients were followed until the end of 1994, with a mean follow-up of 5.6 (0-14) years. Bilateral operations were performed on 356 patients, whereas 248 patients had died with only 1 THA.

The cumulated risk of replacement of the contralateral hip was approximately 0.15 1 year after replacement of the first hip, 0.20 after 2 years, 0.29 after 5 years and 0.47 after 10 years, respectively.

During the follow-up period, the demand for a THA of the contralateral hip continued to be approximately 15 times higher than in the general population.     

T-cell vaccination in multiple sclerosis: update on clinical application and mode of action

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS). Autoreactive T cells specific for myelin antigens are considered to play a prominent role in the initiation of the local inflammatory response, ultimately leading to myelin damage. Several studies indicate that autoreactive T cells are not completely deleted in the thymus, but are part of the normal T cell repertoire. Accidentally activated autoreactive T cells, however, may not automatically lead to autoimmune disease. Several reports support the existence of peripheral regulatory networks that prevent the activation and expansion of pathogenic T cells. Anti-idiotypic and anti-ergotypic T cells are part of this regulatory network and are thought to control autoreactive T cells by recognition of certain clonotypic and ergotypic determinants. These clonotypic networks may not function properly in patients with MS. Immunization with attenuated autoreactive T cells, termed T cell vaccination (TCV), may enhance or restore the regulatory networks to specifically suppress the autoreactive T cells as shown in experimental autoimmune encephalomyelitis (EAE), a commonly used animal model for MS. In the past decade, TCV has been tested for MS in several clinical trails. This review summarizes these clinical trails and updates our current knowledge on the mode of action of T cell vaccination.     

Central command and the cutaneous vascular response to isometric exercise in heated humans

Cutaneous vascular conductance (CVC) decreases during isometric handgrip exercise in heat stressed individuals, and we hypothesized that central command is involved in this response. Seven subjects performed 2 min of isometric handgrip exercise (35% of maximal voluntary contraction) followed by postexercise ischaemia in normothermia and during heat stress (increase in internal temperature ∼1°C). To augment the contribution of central command independent of force generation, on a separate day the protocol was repeated following partial neuromuscular blockade (PNB; i.v. cisatracurium). Forearm skin blood flow was measured by laser-Doppler flowmetry, and CVC was the ratio of skin blood flow to mean arterial pressure. The PNB attenuated force production despite encouragement to attain the same workload. During the heat stress trials, isometric exercise decreased CVC by ∼12% for both conditions, but did not change CVC in either of the normothermic trials. During isometric exercise in the heat, the increase in mean arterial pressure (MAP) was greater during the control trial relative to the PNB trial (31.0 ± 9.8 versus 18.6 ± 6.4 mmHg, P < 0.01), while the elevation of heart rate tended to be lower (19.4 ± 10.4 versus 27.4 ± 8.1 b.p.m., P = 0.15). During postexercise ischaemia, CVC and MAP returned to pre-exercise levels in the PNB trial but remained reduced in the control trial. These findings suggest that central command, as well as muscle metabo-sensitive afferent stimulation, contributes to forearm cutaneous vascular responses in heat stressed humans.     

Molecular epidemiology of hepatitis B virus infections in Denmark.

BACKGROUND: Denmark has a low incidence of acute hepatitis B (HBV) infections but the impact of an increasing number of immigrants with chronic HBV infection on HBV transmission is unknown. OBJECTIVES: To characterise individuals with chronic and acute HBV infection in a defined region and to examine the importance of different risk groups for the current HBV transmission. METHODS: During 2000-2001 all consecutive HBV infected individuals routinely diagnosed through the regional HBV serology laboratory in the County of Funen were classified according to ethnicity, presumed route of transmission and stage of infection based on clinical data mainly supplied by the requesting physician. HBV DNA was sequenced and subjected to phylogenetic analysis. RESULTS: Of 309 identified cases, 91 (29%) were classified as acute infection. HBV DNA sequencing was possible in 54 (59%) of these cases. Phylogenetic analysis showed that HBV isolated from injecting drug users (IDUs) was identical or closely related. Among acute cases acquired in Denmark 89% (74/83) were seen in IDUs (65) or in individuals presumably exposed to IDUs (nine) and phylogenetic analysis corroborated the assumption of IDU related transmission in every case with available sequence data. Among 83 ethnic Danes who acquired their HBV infection in Denmark, no new cases of transmission from immigrants were detected. CONCLUSION: Injecting drug use was the single most important factor for hepatitis B transmission in Denmark. The current Danish vaccination strategy is unable to protect IDUs from HBV infection and IDUs pose a greater risk of HBV transmission to the general population than immigrants.