PubMed Health⌕ Search

Biomedical subjects

P Skinhøj

Publications and source records attributed to P Skinhøj.

At least 19 recordsLinked to original sources
PubMed2005

Invasive group A, B, C and G streptococcal infections in Denmark 1999-2002: epidemiological and clinical aspects.

Group A streptococci (GAS) have been described frequently as an emerging cause of severe invasive infections in population-based surveillance studies, whereas the descriptions of group B, C and G streptococci (GBS, GCS and GGS) have been less frequent. Enhanced surveillance for invasive GAS, GBS, GCS and GGS was performed in Denmark in 1999-2002. A detailed questionnaire was completed for 1237 (98%) of 1260 invasive infections. GAS infections dominated (40%), followed by GGS (32%), GBS (23%) and GCS (6%). Most (74%) patients had predisposing factors, and there were no significant differences between the four serogroups when comparing the prevalence of cancer, diabetes mellitus, chronic heart or lung diseases, immunodeficiency or alcohol abuse. The overall case fatality rate at day 30 was 21%, increasing significantly to 59% for patients with streptococcal toxic shock syndrome (STSS). STSS was significantly more frequent in GAS patients (10%) than in GCS (4%), GBS (2%) and GGS (2%) patients. Regression analyses showed that, despite a younger median age among GAS patients, the probability of developing septic shock and mortality was significantly higher among GAS patients than among GBS and GGS patients. These analyses showed no significant differences between GAS and GCS infections. Invasive infections caused by GAS, GBS, GCS and GGS are still a major challenge for clinicians. Continued epidemiological and microbiological surveillance is important to assess the development of these infections and to improve preventative strategies.

Adolescent↗
PubMed2003

Changing epidemiology of HBV infection in Danish children.

Hepatitis B continues to be a worldwide threat to human health, especially if infection occurs in childhood. Universal vaccination is recommended by WHO, but has not been implemented in the Scandinavian countries, Holland and UK, because of a low incidence rate. However, clinically overt infections are rare in childhood. We therefore performed a nation wide serosurvey for HBV markers in 2428 children aged primarily 6-16 years from 16 primary schools in Denmark. Anti-HBc was found in altogether 20 children (0.8%), 12 of whom were among 144 immigrant children (8.3%) compared to 8 (0.4%) in those born in Denmark. Three of the children, all immigrants, were HBsAg positive indicating chronic infection. At school level no relation of anti-HBc in Danish born children was found to schools with high number of immigrant children or schools with HBsAg positive children indicating a low risk of Hepatitis B transmission in this setting. The results do not support implementation of general vaccination, but stress the need for HBV screening in immigrants as it provides a mean for immunization of close contacts at risk and information on prevention.

Adolescent↗
PubMed2003

T-cell receptor excisional circles, telomere length, proliferation and apoptosis in peripheral blood mononuclear cells of human immunodeficiency virus-infected individuals after 18 months of treatment induced viral suppression.

This study evaluated the effect of highly active antiretroviral therapy (HAART)-induced viral suppression on T-cell receptor excisional circles (TRECs), telomere length, proliferative responses and spontaneous as well as phytohaemagglutinin (PHA)-stimulated lymphocyte apoptosis in 27 human immunodeficiency virus (HIV)-infected individuals followed for 18 months during HAART. Our results show that HAART significantly increased the level of TRECs in CD4+ cells (P = 0.003) after 18 months of almost continuously suppressed HIV-RNA levels. Lymphocyte proliferative responses and apoptosis levels in patients were significantly lower and significantly higher, respectively, compared with healthy controls. The proliferative response and apoptosis levels did not change during follow up. Changes in telomere length were observed in CD4+ and in CD8+ T cells. The study demonstrated that HAART induces normal TREC levels in the CD4+ T-cell pool. However, the other perturbed functions in T cells indicate that immune reconstitution is incomplete and may need longer viral suppression.

Adult↗
PubMed2003

Virological and immunological profiles among patients with undetectable viral load followed prospectively for 24 months.

OBJECTIVE: To quantify HIV-RNA in plasma, in lymphoid tissue and proviral DNA in peripheral blood mononuclear cells and to relate these to immunological markers among patients with plasma viral load counts of </= 200 HIV-RNA copies/mL. METHODS: A prospective study of one hundred and three patients was undertaken with an inclusion criteria of plasma viral load of </= 200 copies/mL. The patients had advanced HIV infection; 25% had developed AIDS. Patients were seen every 6 months for a period of 2 years. RESULTS: The median plasma viral load was < 20 copies/mL with no increase during follow-up. Thirty-one per cent had plasma viral load of </= 20 copies/mL at all visits, 44% had >/= 1 measurement with 21-200 and 25% had >/= 1 sample with plasma HIV-RNA > 200 copies/mL. Lymphoid tissue viral load was low at enrolment and declined further during follow-up. Baseline HIV-DNA and immunoglobulin (IgA) differed significantly between the plasma viral load rebound groups (P < 0.05). CONCLUSION: In this cohort, selected solely on the basis of having a plasma viral load of </= 200 copies/mL, we found stable or declining viral loads in the measured compartments during 2 years of follow-up. Baseline HIV-DNA and IgA levels were higher among patients with less complete virological suppression relative to patients with persistently undetectable plasma HIV-RNA. Hence, a high cellular level of HIV-DNA and high plasma IgA may predict subsequent development of low-grade viraemia.

Adult↗
PubMed2003

Twenty-year survey of the epidemiology of hepatitis B in Denmark: effect of immigration.

Implementation of hepatitis B virus (HBV) vaccination is being considered in Denmark. Therefore, a 20 y survey on the epidemiology of HBV infection was performed. All notified cases of acute HBV infection in Denmark from 1982 to 2002 were reviewed retrospectively and all available data from 1970 to 2001 on the prevalence of hepatitis B surface antigen (HBsAg) in different groups of the Danish population were studied. The notified annual incidence of acute HBV infection has declined from more than 200 cases to fewer than 50 cases in 2001. In the indigenous population there has been a similar decline in prevalence of HBsAg carriers, from 0.15 to 0.03%, but owing to immigration of new HBsAg carriers from developing countries the overall number of carriers has not changed. The small effect of immigration on the incidence of acute HBV infections as well as the decreasing prevalence of HBsAg carriers among Danes should be taken into account when planning new vaccination strategies in Denmark.

Adolescent↗
PubMed2002

Cerebral blood flow, oxidative metabolism and cerebrovascular carbon dioxide reactivity in patients with acute bacterial meningitis.

BACKGROUND: The optimal arterial carbon dioxide tension (P(a)CO(2)) in patients with acute bacterial meningitis (ABM) is unknown and controversial. The objective of this study was to measure global cerebral blood flow (CBF), cerebrovascular CO(2) reactivity (CO(2)R), and cerebral metabolic rates (CMR) of oxygen (O(2)), glucose (glu), and lactate (lac), in patients with ABM and compare the results to those obtained in healthy volunteers. METHODS: We studied 19 patients (17 of whom were sedated) with ABM and eight healthy volunteers (controls). CBF was measured during baseline ventilation and hyperventilation with single-photon emission computed tomography (SPECT) (14 patients) and/or the Kety-Schmidt technique (KS) (11 patients and all controls). In KS studies, CMR was measured by multiplying the arterial to jugular venous concentration difference (a-v D) by CBF. RESULTS: CBF did not differ significantly among groups, although a larger variation was seen in patients than in controls. CO(2)R was not significantly different among groups. At baseline, patients had significantly lower a-v DO(2), CMR(O(2)), CMR(glu), and CMR(lac) than controls. CMR(O(2)) did not change between hyperventilation compared to baseline ventilation, whereas CMR(glu) increased. CONCLUSION: In patients with acute bacterial meningitis, we found variable levels of CBF and cerebrovascular CO(2) reactivity, a low a-v DO(2), low cerebral metabolic rates of oxygen and glucose, and a cerebral lactate efflux. In these patients, a ventilation strategy guided by jugular bulb oximetry and/or repeated CBF measurements may be more optimal in terms of cerebral oxygenation than a strategy aiming at identical levels of P(a)CO(2) for all patients.

Adult↗
PubMed2002

Is ageing associated with a shift in the balance between Type 1 and Type 2 cytokines in humans?

The balance between Type 1 and Type 2 cytokines is important for the outcome of several infectious diseases. As elderly humans show increased morbidity and mortality from infectious diseases, this study tests if ageing is associated with a change towards Type 2 dominance in T cells. Expression of IFN-gamma, and IL-4 was measured in CD4+ and CD8+ T cells by flow cytometry in three groups: young controls (n=28), 81-year-olds (n=22), and centenarians (n=25). The major findings were that the percentage of IFN-gamma+ as well as IL-4+ T cells was increased in aged subjects. Furthermore, after adjusting for decreased lymphocyte counts in the elderly, the concentration in the blood of IFN-gamma+ and IL-4+ CD8+ T cells was still increased in the 81-year-olds. In centenarians, a shift towards a relative dominance of Type 2 cytokine expression was found within CD8+ T cells. Furthermore, the percentage of T cells with cytokine expression was closely correlated to the in vivo expression of CD95 and CD45RO. In conclusion, we found some evidence for an age-related shift towards a Type 2 cytokine profile.

Adult↗
PubMed2002

A 2-dose regimen of a recombinant hepatitis B vaccine with the immune stimulant AS04 compared with the standard 3-dose regimen of Engerix-B in healthy young adults.

An open-label randomized study was undertaken to compare a 2-dose regimen (Months 0 and 6) of hepatitis B surface antigen (HBsAg) vaccine formulated with a novel adjuvant (HBsAg/AS04) with a standard 3-dose regimen (Months 0, 1 and 6) of licensed recombinant HBsAg vaccine in terms of immunogenicity and reactogenicity when administered to healthy subjects aged between 15 and 40 y. At 1 and 6 months after the full vaccination course there was a 100% seroprotection rate (anti-HBs > or = 10 mIU/ml) with the HBsAg/AS04 vaccine, compared with a 99% response rate with the licensed vaccine. The corresponding geometric mean titres were significantly higher for the novel vaccine compared to the standard vaccine: 15,468 and 2,745 mIU/ml at Months 7 and 12 vs. 6,274 and 1,883 mIU/ml, respectively. There was a higher prevalence of local symptoms with the adjuvant vaccine (90% of doses) than with the standard vaccine (48% of doses). However, these symptoms (pain, swelling and redness) were predominantly of mild-to-moderate intensity and resolved rapidly without treatment. A 2-dose regimen of the new HBsAg/AS04 adjuvant vaccine therefore compared favourably to the standard regimen in healthy young adults. It is anticipated that the simplified vaccination schedule may improve compliance and reduce costs.

Adolescent↗
PubMed2002

Activated T lymphocytes disappear from circulation during endotoxemia in humans.

Seventeen volunteers received an intravenous bolus of endotoxin (2 ng/kg of body weight). Endotoxin-induced lymphopenia was constituted mainly by cells with an immature phenotype (CD45RA(+) CD45RO(-)) that were less likely to undergo apoptosis (CD28(+)), whereas cells with the highest rates of disappearance were characterized by an activated phenotype (CD45RA(-) CD45RO(+)) as well as a phenotype linked to apoptosis (CD95(+) CD28(-)). In conclusion, endotoxin-induced lymphopenia reflects the disappearance from the circulation of activated lymphocytes prone to undergo apoptosis.

Adult↗
PubMed2001

Non-Hodgkin lymphoma in HIV-infected patients in the era of highly active antiretroviral therapy.

This study was designed to assess the influence of highly active antiretroviral therapy (HAART) on non-Hodgkin lymphoma (NHL) among patients infected with human immunodeficiency virus (HIV). Within EuroSIDA, a multicenter observational cohort of more than 8500 patients from across Europe, the incidences of NHL and subtypes (Burkitt, immunoblastic, primary brain lymphoma [PBL], and other/unknown histology) were determined according to calendar time of follow-up, and for those who initiated HAART (> or =3 drugs) also time on HAART. Potential predictive factors of NHL were evaluated in Cox proportional hazard models. Over 26 764 person-years of prospective follow-up (PYF) from May 1994 to December 2000, the incidence of NHL decreased from 1.99 (95% confidence interval, 1.51-2.47) before September 1995 to 0.30 (0.19-0.42) cases/100 (PYF) after March 1999 (P <.001). The incidence of all subtypes of NHL decreased significantly and most pronouncedly for PBL. Among patients who started HAART, the incidence of NHL decreased from 0.88 (0.60-1.16) within the first 12 months after starting HAART to 0.45 (0.31-0.60) cases/100 PYF after more than 24 months (P =.004). In an adjusted Cox model for patients on HAART, the latest CD4 cell count and plasma viral load were both significantly associated with diagnosis of NHL; the relative hazard was 1.39 (range, 1.14-1.69) per 50% lower CD4 cell count, and 1.51 (range, 1.21-1.88) per 1 log higher plasma viral load. In conclusion, the incidence of NHL among HIV-infected patients has decreased significantly after the introduction of HAART, and the decline was most pronounced for PBL. After starting HAART, patients with insufficient immunologic and virologic responses were at highest risk of NHL.

Acquired Immunodeficiency Syndrome↗
PubMed2001

Decreased natural killer cell activity is associated with atherosclerosis in elderly humans.

Well-preserved natural killer cell (NK) activity has been associated with successful aging. The aim of the present study was to perform detailed analyses of NK cell function and to investigate the clinical significance of the NK cell number and function in relationship to health in a large cohort of elderly humans. It was tested if the potential of natural cytotoxicity in the blood (evaluated as an index including cytotoxicity per NK cell and the number of circulating NK cells) was preserved in 174 81-year-old humans versus 91 young controls and if NK cell mediated immunity was associated with age-related inflammatory diseases such as atherosclerosis. Elderly people had decreased cytotoxicity per NK cell in short-term but not in long-term assays. Ca(2+) independent cytotoxicity was unaltered, and NK cells maintained their cytotoxic responses to interleukin-2 and interferon-alpha signals. The decreased cytotoxicity per NK cell was not completely counteracted by increased circulating numbers of NK cells in the blood. Elderly people with severe medical disorders had low numbers of circulating NK cells. Furthermore, elderly people with atherosclerosis had low cytotoxicity per NK cell and a high number of circulating neutrophils.

Adult↗
PubMed2001

Hypotension during endotoxemia in aged humans.

BACKGROUND: and objective The aim of this study was to determine possible age-associated differences in human blood pressure regulation during an immunological challenge in healthy subjects. METHODS: Eight healthy young volunteers (median age 24 yr) and nine healthy elderly volunteers (median age 66 yr) received an intravenous bolus injection of Escherichia coli endotoxin (2 ng kg(-1)). Blood pressure, heart rate and core temperature were monitored during the first 7 h. Plasma catecholamine concentrations were measured at hourly intervals. RESULTS: The elderly showed a significantly more pronounced decrease in mean arterial pressure 4-7 h after endotoxin administration compared with the young controls (ANOVA; age x time; P < 0.0005). This mainly reflected a decrease in the systolic blood pressure in the elderly. The heart rate of both groups increased without difference between groups. Increased plasma epinephrine concentrations were found 2-3 h after endotoxin administration in both groups. Five hours after the endotoxin challenge, the epinephrine concentration had returned to control values in the elderly group only, in spite of decreased blood pressure. CONCLUSION: In conclusion, healthy elderly subjects fail to maintain a constant mean arterial pressure in response to the immunological challenge of endotoxemia.

Adult↗
PubMed2001

T-cell mean telomere lengths changes in treatment naïve HIV-infected patients randomized to G-CSF or placebo simultaneously with initiation of HAART.

The effect of highly active antiretroviral therapy (HAART) and granulocyte colony stimulating factor (G-CSF) on mean telomere restriction fragment (TRF) length of peripheral blood mononuclear cells (PBMC) was examined in 11 treatment naïve human immunodeficiency virus (HIV)-infected individuals with a CD4+ T-cell count < 350 cells/mm3. Patients were randomized to HAART combined with G-CSF thrice weekly for 12 weeks (n = 6) or placebo (n = 5). An increase in the mean TRF lengths was observed in PBMC of patients on HAART after 24 weeks of treatment mainly owing to increased mean CD8+ T-cell TRF lengths. However, in the group of patients on HAART combined with G-CSF no changes of PBMC mean TRF length was observed during treatment or during 12 weeks of follow-up. The mean CD4+ T-cell TRF length did not change in any of the two groups. These results confirm that HAART induces mainly the lengthening of the mean CD8+ T-cell TRF length. However, G-CSF given simultaneously with HAART induces an inhibition of the expected lengthening in mean TRF length. These results do therefore not support the use of adjuvant G-CSF treatment simultaneously when initiating HAART and should further be evaluated before use in non-neutropenic HIV-infected patients.

Antiretroviral Therapy, Highly Active↗
PubMed2001

The syndrome of inappropriate secretion of antidiuretic hormone and fluid restriction in meningitis--how strong is the evidence?

In patients with meningitis, fluid restriction is recommended to counter the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) and to reduce cerebral oedema. However, any effects of an increased plasma level of ADH upon cerebral oedema would be due not to fluid retention but to hypoosmolality. In a literature review of fluid and electrolyte disturbances and the effect of fluid therapy in bacterial/tuberculous meningitis, the prevalence of hyponatraemia, hypoosmolality and SIADH varied considerably; apparently, non-osmotic stimuli for the secretion of ADH, e.g. intracranial hypertension and hypovolaemia, were present in most patients. Neither clinical nor experimental studies have confirmed that fluid restriction reduces the cerebral oedema in meningitis. Furthermore, compared with maintenance therapy, fluid restriction did not improve outcome in a randomized controlled study. Thus, we find no evidence to support the use of fluid restriction in patients with meningitis. Fluid therapy in acute bacterial meningitis should aim at avoiding hypovolaemia and hypoosmolality based on the assumptions that (i) ADH is increased by non-osmotic stimuli; (ii) elevated ADH is less important for cerebral oedema than severe hypoosmolality, which may in itself induce or aggravate oedema; (iii) maintenance fluid therapy aiming at isoosmolality will not worsen neurological outcome; and (iv) hypovolaemia is difficult to detect, and detrimental for cerebral perfusion, in these patients.

Animals↗
PubMed2001

Ageing is associated with a prolonged fever response in human endotoxemia.

The purpose of this study was to investigate whether an age-associated impaired acute-phase response exists. Nine healthy elderly volunteers (median, 66 years; range, 61 to 69 years) and eight young controls (median, 24 years; range, 20 to 27 years) were given an intravenous bolus of endotoxin (2 ng/kg). The rectal temperature was monitored continuously, and blood samples for cytokine measurements were obtained before endotoxin administration as well as 0.5, 1, 1.5, 2, 3, 4, 8, 12, and 24 h after the injection. The elderly subjects showed a more prolonged fever response compared to the young controls. Levels of tumor necrosis factor alpha (TNF-alpha), soluble TNF receptors (sTNFR-I), interleukin-6 (IL-6), IL-8, IL-10, and IL-1 receptor antagonist (IL-1ra) in plasma increased markedly following endotoxin administration in both groups. The elderly group showed larger initial increases in TNF-alpha and sTNFR-I levels and prolonged increased levels of sTNFR-I. Monocyte concentrations decreased in both groups, with the elderly group showing a more rapid decrease and a slower subsequent increase than did the young group. Furthermore, the elderly group had a more rapid increase in C-reactive protein levels than did the young group. In conclusion, ageing is associated with an altered acute-phase response including initial hyperreactivity, prolonged inflammatory activity, and prolonged fever response.

Acute-Phase Reaction↗