Per-Erik Isberg

Inhibition of HIV-1 Disease Progression by Contemporaneous HIV-2 Infection

BACKGROUND Progressive immune dysfunction and the acquired immunodeficiency syndrome (AIDS) develop in most persons with untreated infection with human immunodeficiency virus type 1 (HIV-1) but in only approximately 20 to 30% of persons infected with HIV type 2 (HIV-2); among persons infected with both types, the natural history of disease progression is poorly understood. METHODS We analyzed data from 223 participants who were infected with HIV-1 after enrollment (with either HIV-1 infection alone or HIV-1 and HIV-2 infection) in a cohort with a long follow-up duration (approximately 20 years), according to whether HIV-2 infection occurred first, the time to the development of AIDS (time to AIDS), CD4+ and CD8+ T-cell counts, and measures of viral evolution. RESULTS The median time to AIDS was 104 months (95% confidence interval [CI], 75 to 133) in participants with dual infection and 68 months (95% CI, 60 to 76) in participants infected with HIV-1 only (P=0.003). CD4+ T-cell levels were higher and CD8+ T-cell levels increased at a lower rate among participants with dual infection, reflecting slower disease progression. Participants with dual infection with HIV-2 infection preceding HIV-1 infection had the longest time to AIDS and highest levels of CD4+ T-cell counts. HIV-1 genetic diversity was significantly lower in participants with dual infections than in those with HIV-1 infection alone at similar time points after infection. CONCLUSIONS Our results suggest that HIV-1 disease progression is inhibited by concomitant HIV-2 infection and that dual infection is associated with slower disease progression. The slower rate of disease progression was most evident in participants with dual infection in whom HIV-2 infection preceded HIV-1 infection. These findings could have implications for the development of HIV-1 vaccines and therapeutics. (Funded by the Swedish International Development Cooperation Agency-Swedish Agency for Research Cooperation with Developing Countries and others.).

Fetal hemoglobin and α1-microglobulin as first- and early second-trimester predictive biomarkers for preeclampsia

OBJECTIVE The aim of this study was to evaluate fetal hemoglobin (HbF) and α(1)-microglobulin (A1M) in maternal serum as first-trimester biomarkers for preeclampsia (PE). STUDY DESIGN The design was a case-control study. We included 96 patients in the first trimester of pregnancy (60 with PE and 36 controls). Venous serum samples were analyzed for HbF and total hemoglobin (Hb) by enzyme-linked immunosorbent assay and for A1M by radioimmunoassay. Sensitivity and specificity was calculated by logistic regression and receiver operating characteristic curve analysis. RESULTS The HbF/Hb ratio and A1M concentration were significantly elevated in serum from women with subsequent development of PE (P < .0001). The optimal sensitivity and specificity was obtained using the biomarkers in combination; 69% sensitivity for a 5% screen positive rate and 90% sensitivity for a 23% screen positive rate. CONCLUSION The study suggests that HbF/Hb ratio in combination with A1M is predictive biomarkers for PE.

High Proteinase 3-Anti-Neutrophil Cytoplasmic Antibody (ANCA) Level Measured by the Capture Enzyme-Linked Immunosorbent Assay Method Is Associated with Decreased Patient Survival in ANCA-Associated Vasculitis with Renal Involvement

Wegener granulomatosis (WG) and microscopic polyangiitis (MP), diseases associated with antineutrophil cytoplasmic antibodies (ANCA), had an extremely poor prognosis before the introduction of cyclophosphamide and corticosteroids for their treatment. However, there is still reduced patient survival, and some studies have documented severe side effects of the immunosuppressants used. This 10-yr follow-up study assessed 117 consecutive patients with WG or MP with biopsy-confirmed renal involvement. The cumulative relative patient survival was lower: 0.664 for women and 0.648 for men. The causes of death (n = 64) were in most cases registered as associated with the vasculitic disease. Analysis of possible predictive factors for patient survival by multiple Cox regression analysis revealed that a very high level of proteinase 3 (PR3)-ANCA measured by the capture ELISA method, a diagnosis of MP, and older age were factors predicting poorer patient survival. High levels of B-thrombocytes at time of diagnosis were associated with a better prognosis. For patients surviving the first year, remission-sustaining therapy with azathioprine for longer than 12 mo was associated with improved patient survival. Thirty-nine patients developed end-stage renal failure. Elevated serum creatinine at time of diagnosis and a very high level of PR3-ANCA by capture ELISA were factors predicting a higher risk for renal failure during follow-up. The epitope on PR3 assessed by capture ELISA needs to be further analyzed and explored: it seemed to implicate poorer patient and renal survival in WG or MP with renal involvement.

Concentration dependence of adsorption from human whole resting saliva at solid/liquid interfaces: An ellipsometric study

The rates and plateau values of adsorption at the solid/ liquid interface from human whole resting saliva from three male donors were studied in vitro. The influence of saliva concentration, the total protein content and the wettability of the exposed solids was investigated. Ellipsometry was used to study the rate and plateau values of the adsorption process in situ. The solid surfaces used were hydrophilic, negatively charged, silica and hydrophobic methylated silica. Salivary films were formed by adsorption from solutions of 0.05%, 0.10%, 0.20%, 0.50%, 1.0% and 2.0% (v/v) saliva in phosphate buffered saline. The results revealed that adsorption onto both types of surfaces was a rapid and, as expected, a concentration dependent process. The adsorbed amounts were in the range of monomolecular layers and were found to be larger onto the hydrophobic than the hydrophilic surfaces (p≤0.0062). A strong concentration dependence was denoted in all cases (p< 0.0001). Inter‐individual differences were found not t...

Impact of Periodontal Disease Experience on Oral Health-Related Quality of Life

BACKGROUND Periodontal research has traditionally focused on the site level, regarding etiology, pathogenesis, and treatment outcome. Recently, some studies have indicated that the presence of periodontal disease is associated with reduced quality of life. The aim of this study is to investigate the impact of periodontal disease experience on the quality of life. METHODS This cross-sectional study includes 443 individuals. Clinical and radiographic examinations were performed; in conjunction, the oral health-related quality of life of all participants was assessed using the Swedish short-form version of the Oral Health Impact Profile (OHIP-14). Based on marginal bone loss, measured on radiographs, three different groups were identified: participants with loss of supporting bone tissue of less than one third of the root length (BL-), loss of supporting bone tissue of one third or more of the root length in <30% of teeth (BL), or loss of supporting bone tissue of one third or more of the root length in ≥ 30% of teeth (BL+). RESULTS The effect of periodontal disease experience on quality of life was considerable. For the BL- group, the mean OHIP-14 score was 3.91 (SD: 5.39). The corresponding mean values were 3.81 (SD: 5.29) for the BL group and 8.47 (SD: 10.38) for the BL+ group. The difference among all groups was statistically significant (P ≤ 0.001). A comparison among the mean OHIP-14 scores in the different groups (BL-, BL, and BL+) revealed significant differences in six of seven conceptual domains. CONCLUSIONS The BL+ individuals experienced reduced quality of life, expressed as the OHIP-14 score, compared with the BL and BL- participants.

Caries risk profiles in schoolchildren over 2 years assessed by Cariogram

BACKGROUND Caries risk assessment is an important tool in clinical decision making. AIM To evaluate longitudinal changes in caries risk profiles in a group of schoolchildren in relation to caries development. DESIGN The Cariogram model was used to create caries risk profiles and to identify risk factors in 438 children being 10-11 years at baseline. The assessment was repeated after 2 years and the caries increment was recorded. The frequency of unfavourable risk factors were compared between those considered at the lowest and the highest risk. RESULTS Fifty percent of the children remained in the same risk category after 2 years. One third of the children were assessed in a higher-risk category while 18.4% showed a lower risk. Those with increased risk compared with baseline developed significantly more caries than those with an unchanged risk category. The most frequent unfavourable risk factors among those with high risk at baseline were high-salivary mutans streptococci and lactobacilli counts as well as frequent meals. CONCLUSION Half of the children showed a changed risk category after 2 years, for better or for worse, which suggests that regular risk assessments are needed in order to make appropriate decisions on targeted preventive care and recall intervals.

Inter-rater Reliability and Between-days Repeatability of Eight Physical Performance Tests

Results of reliability studies on physical performance tests are often conflicting. The main purpose of this study was to analyse the inter-rater reliability and between-days repeatability of physical performance tests on a female working population. Twenty-two nursing aides/ assistant nurses were tested twice, with, on average, a 5-day interval. Seventeen of these were tested again, after an average of 16 days. Isometric endurance of the neck flexors, abdominal, back and shoulder muscles, standing balance and two lifting tests (lumbar and cervical Progressive Isoinertial Lifting Evaluation {PILE} tests) were evaluated. Intra-class correlation coefficient (ICC), standard error of measurement (SEM), coefficient of variation (CV) and limits of agreement (LOA and LOA ratio ) were calculated. The inter-rater reliability was high for all tests. The between-days repeatability, however, differed depending on the statistical method employed. Only one of the tests - the cervical PILE test - was considered reliable between-days. Muscular endurance tests, the lumbar PILE test and standing balance tests, as performed in this study, did not give reliable between-days results.

Faster Progression to AIDS and AIDS-Related Death Among Seroincident Individuals Infected With Recombinant HIV-1 A3/CRF02_AG Compared With Sub-subtype A3

BACKGROUND Human immunodeficiency virus type 1 (HIV-1) is divided into subtypes and circulating recombinant forms (CRFs) but the impact of subtype/CRF on disease progression is not fully understood. METHODS We determined the HIV-1 subtype/CRF of 152 seroincident individuals from Guinea-Bissau, based on the C2-V3 region of env. Disease progression was measured as time from estimated seroconversion to AIDS and AIDS-related death. Hazard ratios (HRs) were calculated using a Cox proportional hazard model, adjusting for gender and age at seroconversion. RESULTS The major subtypes/CRFs identified were CRF02_AG (53%), A3 (29%), and A3/02 (a recombinant of A3 and CRF02_AG) (13%). Infection with A3/02 was associated with a close to 3-fold increased risk of AIDS and AIDS-related death compared to A3 (HR = 2.6 [P = 0.011] and 2.9 [P = 0.032], respectively). The estimated time from seroconversion to AIDS and AIDS-related death was 5.0 and 8.0 years for A3/02, 6.2 and 9.0 years for CRF02_AG, and 7.2 and 11.3 years for A3. CONCLUSION Our results show that there are differences in disease progression between HIV-1 A-like subtypes/CRFs. Individuals infected with A3/02 have among the fastest progression rates to AIDS reported to date. Determining the HIV-1 subtype of infected individuals could be important in the management of HIV-1 infections.

Mortality of Anxiety Syndromes in a Normal Population

The mortality of anxiety syndromes between 1972 and 1992 was investigated in a prospective study of a normal population, the 1947 Lundby cohort. 121 persons with anxiety according to the Lundby definition (Anx), and 74 persons with panic disorder with/without agoraphobia (PD-Ag) according to the DSM-III-R, all of them developing their first episode between 1947 and 1972, were analyzed with regard to general mortality and special cause of death. Sex- and age-specific mortality rates for these groups were calculated and compared with the corresponding rates of the cohorts 1,877 remaining subjects without first episodes of Anx/PD-Ag. In contrast to the females, the annual rates of general mortality in males with Anx/PD-Ag were 1.9/2.2 times higher in the age group 65-84 years, compared with the rates of the non-Anx/PD-Ag groups. They also had an increase in death due to circulatory disorders, most pronounced in males with PD-Ag before the age of 65. There were no suicides in any of the Anx/PD-Ag groups during the observation period.

An in vitro study of initial adsorption from human parotid and submandibular/sublingual resting saliva at solid/liquid interfaces

The influence of saliva concentration, saliva total protein content and the wetting characteristics of exposed solids on in vitro film formation was studied by the technique of in situ ellipsometry. The rates and plateau values of adsorption (45 min) at solid/liquid interfaces (hydrophilic silica and hydrophobic methylated silica surfaces) were determinated for human parotid (HPS) and submandibular/sublingual (HSMSLS) resting saliva solutions (0.1 and 1.0%, (v/v), saliva in phosphate buffered saline). Adsorption rates were related to a model assuming mass transport through an unstirred layer adjacent to the surface. The results showed that the adsorption was rapid, concentration dependent and higher on hydrophobic than on hydrophilic surfaces. Analysis of the influence of protein concentration on the adsorbed amounts demonstrated an interaction between protein concentration and the two surfaces for HPS and HSMSLS, respectively. This may indicate differences in binding mode. Inter‐individual differences were found not to be significant at the 1% level of probability. Comparison of the observed adsorption and calculated diffusion rates suggest that on hydrophilic surfaces initial adsorption of proteins diffusing at rates corresponding to those of statherin and aPRPs takes place, whereas on hydrophobic surfaces lower molecular mass compounds appear to be involved.