Unsuccessful treatment of chronic norovirus infection with enteral immunoglobulin in patients with common variable immunodeficiency, case report.

Background: Norovirus gastroenteritis is commonly an acute infection that lasts 2-3 days, but in immunocompromised patients norovirus can cause a chronic gastroenteritis lasting for years. Norovirus replicates in the gastrointestinal tract, but the pathway of viral clearance is not yet known. Promising results of enterally administered immunoglobulin in the treatment of chronic norovirus gastroenteritis in immunocompromised patients have previously been published. Case presentation: We report two individuals with common variable immunodeficiency and chronic debilitating norovirus gastroenteritis. Both patients were treated with enterally administered immunoglobulin via a duodenal feeding tube as other treatment modalities have been unsuccessful. The patients did not experience any immediate or long-term benefit of enterally administered immunoglobulin. Conclusion: Despite previous case reports of successful treatment of chronic norovirus infection among immunocompromised patients with enterally administered immunoglobulin, these two patients experienced no benefit of the treatment. This demonstrates the need for further research in treatment of chronic norovirus infection in immunocompromised patients.

Cardiac chamber volumes and left ventricular mass in people living with HIV and matched uninfected controls.

OBJECTIVES: People living with HIV (PLWH) have increased risk of cardiovascular diseases compared with uninfected populations. We assessed structural cardiac abnormalities and their associated risk factors in well-treated PLWH and uninfected controls using multidetector computed tomography (MDCT). METHODS: People living with HIV and age- and sex-matched uninfected controls underwent MDCT to determine left atrial volume (LAV), left ventricular diastolic volume (LVDV), right ventricular diastolic volume (RVDV) and left ventricular mass (LVM). All outcomes were indexed to body surface area (BSA) (LAVi, LVDVi, RVDVi and LVMi). RESULTS: A total of 592 PLWH and 1184 uninfected controls were included in the study. PLWH had smaller mean (SD) LAVi [40 (8) vs. 41 (9) mL/m2 ; P = 0.002] and LVDVi [61 (13) vs. 65 (14) mL/m2 ; P < 0.001] but larger RVDVi [89 (18) vs. 86 (17) mL/m2 ; P < 0.001] than uninfected controls. HIV was independently associated with 7 mL (95% CI: -10 to -3) smaller LVDV, and with 12 mL (95% CI: 8-16) larger RVDV, and 4 g (95% CI: 1-6) larger LVM after adjustment for cardiovascular risk factors and BSA. Large RVDV in PLWH was not associated with obstructive lung function. CONCLUSIONS: HIV was independently associated with smaller LVDV and larger RVDV and LVM. Alterations in cardiac chamber volumes in PLWH were mainly minor. The clinical impact of these findings is uncertain, but it seems unlikely that alterations in cardiac chamber volumes explain the increased burden of cardiovascular disease previously observed in PLWH.

Risk factors during pregnancy and birth-related complications in HIV-positive versus HIV-negative women in Denmark, 2002-2014.

OBJECTIVES: We aimed to compare risk factors for adverse pregnancy outcomes in women living with HIV (WLWH) with those in women of the general population (WGP) in Denmark. Further, we estimated risk of pregnancy- or birth-related complications. METHODS: A retrospective cohort study including all WLWH who delivered a live-born child from 2002 to 2014 and WGP, matched by origin, age, year and parity, was carried out. We compared risk factors during pregnancy and estimated risk of pregnancy- and birth-related complications using multivariate logistic regression. RESULTS: A total of 2334 pregnancies in 304 WLWH and 1945 WGP were included in the study. WLWH had more risk factors present than WGP during pregnancy: previous caesarean section (CS) (24.7% versus 16.3%, respectively; P = 0.0001), smoking (14.2% versus 7.5%, respectively; P = 0.0001) and previous perinatal/neonatal death (2.3% versus 0.9%, respectively; P = 0.03). We found no difference between groups regarding gestational diabetes, hypertensive disorders, low birth weights or premature delivery. More children of WLWH had intrauterine growth retardation (IUGR) [adjusted odds ratio (aOR) 1.9; 95% confidence interval (CI) 1.1-3.2; P = 0.02]. Median gestational age and birth weight were lower in children born to WLWH. WLWH had a higher risk of emergency CS (EmCS) (aOR 1.6; 95% CI 1.2-2.1; P = 0.0005) and postpartum haemorrhage (aOR 1.4; 95% CI 1.0-1.9; P = 0.02) but not infection, amniotomy, failure to progress, low activity-pulse-grimace-appearance-respiration (APGAR) score or signs of asphyxia. CONCLUSIONS: WLWH had more risk factors present during pregnancy, similar risks of most pregnancy- and birth-related complications but a higher risk of postpartum haemorrhage and EmCS compared with WGP. Children born to WLWH had lower median birth weights and gestational ages and were at higher risk of IUGR.

Coronary artery calcium and intima-media thickness are associated with level of cytomegalovirus immunoglobulin G in HIV-infected patients.

Coinfection with cytomegalovirus (CMV) may be involved in cardiovascular disease in HIV-infected patients. We found that higher level of CMV immunoglobulin G (IgG) was independently associated with an increased risk of coronary artery calcium and higher intima-media thickness in HIV-infected patients but not in healthy controls after adjustment for other cardiovascular risk factors and levels of herpes viridae IgG.

Association between smoking status assessed with plasma-cotinine and inflammatory and endothelial biomarkers in HIV-positive and HIV-negative individuals.

OBJECTIVES: Smoking is a major contributor to mortality and morbidity in HIV-positive individuals. Our primary objective was to evaluate the association between smoking status determined by plasma cotinine (P-cotinine) concentration and inflammatory and endothelial biomarkers in HIV-positive versus HIV-negative individuals. METHODS: We studied eight inflammatory/endothelial biomarkers [high-sensitivity C-reactive protein (hsCRP), E-selectin, soluble vascular cell adhesion molecule 1 (sVCAM-1), soluble intercellular adhesion molecule 1 (sICAM-1), matrix metallopeptidase 9 (MMP-9), myeloperoxidase (MPO), tissue type plasminogen activator inhibitor 1 (tPAI) and endothelin] in 105 HIV-positive individuals and 105 HIV-negative individuals matched on age, sex and self-reported smoking status. Smoking status was determined using P-cotinine (a concentration > 14 ng/mL was defined as demonstrating exposure to smoke). We used linear regression models to (1) examine the association between smoking status and inflammatory/endothelial biomarkers in HIV-positive compared with HIV-negative individuals, and (2) to determine whether there was evidence to suggest that the impact of smoking status on the biomarkers differed between HIV-positive and HIV-negative individuals. RESULTS: Of the eight biomarkers, smokers had increased hsCRP, sICAM-1 and MMP-9 concentrations irrespective of HIV status and increasing P-cotinine concentration was associated with increasing hsCRP concentration. We found no interaction between smoking and HIV status. HIV infection was associated with increased hsCRP, E-selectin, sVCAM-1, sICAM-1 and MMP-9 concentrations. Self-reported smoking status differed substantially from smoking status assessed with P-cotinine. CONCLUSIONS: Several biomarkers were associated with smoking status and HIV status. However, our data do not indicate that the effects of smoking on the biomarkers differ between HIV-positive and HIV-negative individuals.

Infectious meningitis and encephalitis in adults in Denmark: a prospective nationwide observational cohort study (DASGIB).

OBJECTIVES: To monitor epidemiological trends of infectious meningitis (bacterial and viral) and encephalitis in Denmark. METHODS: Nationwide prospective observational study of all cases of proven community-acquired infectious meningitis and encephalitis in adults treated in all infectious diseases departments in Denmark from 1 January 2015 to 30 June 2016. We included data on symptoms, aetiology, treatment and outcome assessed by the Glasgow Outcome Scale (GOS) 30 days after discharge. GOS 1-4 was categorized as unfavourable outcome. RESULTS: During 18 months of observation, we identified 252 cases of viral meningitis (3.6/100 000/year), 214 cases of bacterial meningitis (3.1/100 000/year) and 96 cases of infectious encephalitis (1.4/100 000/year). In bacterial meningitis, Streptococcus pneumoniae was the most frequent infectious agent (n = 101) followed by Staphylococcus aureus (n = 24) and ß-haemolytic streptococci (n = 14). Meningococcal meningitis was rare (n = 11). In encephalitis, herpes simplex virus type 1 was most common (n = 37) followed by varicella zoster virus (n = 20), whereas varicella zoster virus (n = 61) was most common in viral meningitis followed by enterovirus (n = 50) and herpes simplex virus type 2 (n = 46). Case fatality and unfavourable outcome occurred in 31/214 (15%) and 96/214 (45%) with bacterial meningitis and in 5/96 (5%) and 55/89 (62%) with encephalitis. For viral meningitis, unfavourable outcome occurred in 41/252 (17%). CONCLUSIONS: The epidemiology and clinical presentation of the examined central nervous system infections differed considerably and bacterial meningitis was more frequent than previously estimated. Overall prognosis remains poor for bacterial meningitis and encephalitis. Prospective nationwide clinical databases of central nervous system infections may be superior to epidemiological monitoring based on notifications or laboratory systems.

Assessment of mode of delivery and predictors of emergency caesarean section among women living with HIV in a matched-pair setting with women from the general population in Denmark, 2002-2014.

OBJECTIVES: We aimed to assess mode of delivery and predictors of emergency caesarean section (EmCS) in women living with HIV (WLWH) in a matched-pair setting with women from the general population (WGP) in Denmark. Further, we analysed birth plan in WLWH. METHODS: All WLWH giving birth to live-born children from 2002 to 2014 were included in the study. Data were retrieved from medical records and national registries. WLWH were matched 1:5 by age, birth year, parity and ethnicity to WGP. Multivariate logistic regression was used to estimate predictors. RESULTS: We included 389 WLWH and 1945 WGP in the study. At delivery, all WLWH were on antiretroviral therapy and 85.6% had HIV RNA <40 HIV-1 RNA copies/mL. Mean age was 32.7 years [95% confidence interval (CI) 32.1-33.2 years]. Mode of delivery differed significantly between WLWH and WGP [vaginal delivery, 33.4% versus 73.3%, respectively; elective caesarean section (ECS), 40.6% versus 9.7%, respectively; EmCS, 26% versus 17%, respectively; P < 0.0001]. Age > 40 years [adjusted odds ratio (aOR) 2.3; 95% CI 1.5-3.5], asphyxia (aOR 3.2; 95% CI 2.4-4.1), delivery during the evening and at night [aOR 2.3 (95% CI 1.7-3.0) and aOR 2.0 (95% CI 1.5-2.7), respectively], preterm delivery (aOR 3.8; 95% CI 2.6-5.6) and premature rupture of membranes (aOR 3.0; 95% CI 2.1-4.4) predicted EmCS. WLWH had a higher risk of EmCS compared with WGP [2002-2006, aOR 2.0 (95% CI 1.2-3.3); 2007-2008, aOR 2.9 (95% CI 1.4-5.9); 2009-2014, aOR 2.6 (95% CI 1.7-3.9)]. After 2007, more than half of WLWH planned to deliver vaginally. Prior caesarean section was associated with ECS (aOR 11.0; 95% CI 4.5-26.8). No mother-to-child transmission occurred. CONCLUSIONS: Increasing numbers of WLWH deliver vaginally. Despite virological suppression, more WLWH plan and deliver by ECS than WGP. WLWH had a twofold higher risk of EmCS compared with WGP.

Soluble urokinase plasminogen activator receptor (suPAR) is a novel, independent predictive marker of myocardial infarction in HIV-1-infected patients: a nested case-control study.

OBJECTIVES: Patients infected with HIV are at increased risk of myocardial infarction (MI). Increased plasma levels of the inflammatory biomarker soluble urokinase plasminogen activator receptor (suPAR) have been associated with increased risk of cardiovascular diseases (CVD), including MI in the general population. We tested suPAR as a predictive biomarker of MI in HIV-1-infected individuals. METHODS: suPAR levels were investigated in a nested case-control study of 55 HIV-1-infected cases with verified first-time MI and 182 HIV-1-infected controls with no known CVD. Controls were matched for age, gender, duration of antiretroviral therapy (ART), smoking and no known CVD. suPAR was measured in the four plasma samples available for each patient at different time-points; 1, Before initiation of ART; 2, 3 months after initiation of ART; 3, 1 year before the case's MI; and 4, The last sample available before the case's MI. RESULTS: In unadjusted conditional regression analysis, higher levels of suPAR were associated with a significant increase in risk of MI at all time-points. Patients in the third and fourth suPAR quartiles had a three- to 10-fold higher risk of MI compared to patients in the lowest suPAR quartile at all time-points. suPAR remained a strong significant predictor of MI, when adjusting for HIV-1 RNA, total cholesterol, triglycerides and high-density lipoprotein. CONCLUSION: Elevated suPAR levels were associated with increased risk of MI in HIV-infected patients, suggesting that suPAR could be a useful biomarker for prediction of first-time MI in this patient group, even years before the event.

Incidence of cervical dysplasia and cervical cancer in women living with HIV in Denmark: comparison with the general population.

OBJECTIVES: Women living with HIV (WLWH) are reportedly at increased risk of invasive cervical cancer (ICC). A recent publication found that WLWH in Denmark attend the national ICC screening programme less often than women in the general population. We aimed to estimate the incidence of cervical dysplasia and ICC in WLWH in Denmark compared with that in women in the general population. METHODS: We studied a nationwide cohort of WLWH and a cohort of 15 age-matched women per WLWH from the general population for the period 1999-2010. Pathology samples were obtained from The Danish Pathology Data Bank, which contains nationwide records of all pathology specimens. The cumulative incidence and hazard ratios (HRs) for time from inclusion to first cervical intraepithelial neoplasia (CIN)/ICC and time from first normal cervical cytology result to first CIN/ICC were estimated. Sensitivity analyses were performed to include prior screening outcome, screening intensity and treatment of CIN/ICC in the interpretation of results. RESULTS: We followed 1140 WLWH and 17 046 controls with no prior history of ICC or hysterectomy for 9491 and 156 865 person-years, respectively. Compared with controls, the overall incidences of CIN1 or worse (CIN1+), CIN2+ and CIN3+, but not ICC, were higher in WLWH and predicted by young age and a CD4 count < 200 cells/µL. In women with normal baseline cytology, incidences of CIN1+ and CIN2+ were higher in WLWH. However, when we compared subgroups of WLWH and controls where women in both groups were adherent to the national ICC screening programme and had a normal baseline cytology, incidences of CIN and ICC were comparable. CONCLUSIONS: Overall, WLWH developed more cervical disease than controls. Yet, in WLWH and controls adherent to the national ICC screening programme and with normal baseline cytology, incidences of CIN and ICC were comparable.

Laboratory exposure to Brucella melitensis in Denmark: a prospective study.

Brucella species are a frequent cause of laboratory-acquired infections. This report describes the handling of a laboratory exposure of 17 laboratory staff members exposed to Brucella melitensis in a large microbiology laboratory in a brucella-non-endemic area. We followed the US Centers for Disease Control and Prevention guidelines, but, of 14 staff members classified as high-risk exposure, none accepted post-exposure prophylaxis. However, in a period of 6 months of follow-up, none of the exposed laboratory workers developed brucellosis and all obtained sera were negative for antibrucella antibodies. We therefore question the value of routine serological follow-up.

Prevention of mother-to-child transmission of HIV in Denmark, 1994-2008.

OBJECTIVES: The aim of this study was to describe trends in the management of pregnancies in HIV-infected women and their outcomes over a 14-year period in Denmark on a national basis. METHODS: The study was a retrospective cohort study of all HIV-infected women in Denmark giving birth to one or more children between 1 June 1994 and 30 June 2008. RESULTS: We identified 210 HIV-infected women with 255 pregnancies, ranging from 7 per year in 1995 to 39 per year in 2006. Thirty per cent of the women were Caucasian and 51% were Black African. Knowledge of HIV status before pregnancy increased from 8% (four of 49) in 1994-1999 to 80% (164 of 206) in 2000-2008. Only 29% (53 of 183) of the women chose to consult an infectious disease specialist when planning pregnancy, while 14% (27 of 199) received assistance with fertility. The proportion of women on antiretroviral therapy (ART) increased from 76% (37 of 49) in 1994-1999 to 98% (201 of 206) in 2000-2008. Vaginal deliveries ranged from 0 in 2003 to 35% of pregnancies in 2007. Mother-to-child transmission (MTCT) of HIV decreased from 10.4% in 1994-1999 to 0.5% in 2000-2008. All women giving birth to an HIV-positive child were diagnosed with HIV during or after delivery and did not receive prophylactic ART. CONCLUSIONS: The annual number of HIV pregnancies increased fivefold during this 14-year period and substantial changes in pregnancy management were seen. No woman treated according to the national guidelines, i.e. ART before week 22, intravenous zidovudine (ZDV) during labour, neonatal ZDV for 4 to 6 weeks and no breastfeeding, transmitted HIV to her child.

Changes in biomarkers of cardiovascular risk after a switch to abacavir in HIV-1-infected individuals receiving combination antiretroviral therapy.

OBJECTIVES: To investigate, using a longitudinal design, whether biomarkers of cardiovascular risk change after a switch to an abacavir (ABC)-containing regimen in HIV-1-infected individuals already receiving combination antiretroviral therapy (ART). METHODS: Thirty-five HIV-1-infected individuals who switched ART to an ABC-containing regimen were identified. Twenty-two HIV-1-infected individuals who switched ART from and to a non-ABC-containing regimen served as controls. Plasma concentrations of soluble vascular cell adhesion molecule 1 (sVCAM-1), soluble intercellular adhesion molecule 1 (sICAM-1), matrix metallopeptidase 9 (MMP9), myeloperoxidase (MPO) and high sensitivity C-reactive protein (hs-CRP) were measured in blood samples before the switch in ART, and 3 months and 12 months afterwards. Log10-transformed data were compared with paired t-tests. RESULTS: Median MMP9 increased from 45.5 to 64.4 microg/mL after 3 months of ABC exposure (P = 0.011) and remained increased after 12 months (64.2 microg/mL; P = 0.013). MPO increased from median 8.8 to 10.4 microg/mL (P = 0.036) after 3 months of ABC exposure but was not increased after 12 months of exposure (9.1 microg/mL). hs-CRP increased from 3.3 to 4.2 microg/mL after 3 months (P = 0.031) but was not increased after 12 months of exposure (2.8 microg/mL). Neither sVCAM-1 nor sICAM-1 changed after the initiation of ABC. No changes were observed in the control group. CONCLUSIONS: MMP9, MPO and hs-CRP all increased after a switch in ART to an ABC-containing regimen. This indicates increased cardiovascular risk in viral load-suppressed HIV-1-infected individuals switching to ABC and proposes a proinflammatory potential as the underlying pathogenetic mechanism.

Reduction in circulating markers of endothelial dysfunction in HIV-infected patients during antiretroviral therapy.

OBJECTIVES: Antiretroviral therapy (ART) in HIV-infected patients is associated with increased cardiovascular risk. Circulating markers of endothelial dysfunction may be used to study early atherogenesis. The aim of our study was to investigate changes in such markers during initiation of ART. METHODS: In 115 HIV-positive treatment-naïve patients, plasma lipids, E-selectin, soluble intercellular adhesion molecule 1 (sICAM-1), soluble vascular cell adhesion molecule 1 (sVCAM-1), tissue-type plasminogen activator inhibitor 1 (tPAI-1) and high-sensitivity C-reactive protein (hsCRP) were measured before and after 2 and 14 months of ART. A control group of 30 healthy subjects was included. Values are mean+/-standard error of the mean. RESULTS: Prior to treatment, HIV-infected patients had elevated levels of sICAM-1 (296+/-24 vs. 144+/-12 ng/mL), tPAI-1 (18 473+/-1399 vs. 5490+/-576 pg/mL) and hsCRP (28 060+/-5530 vs. 6665+/-2063 ng/mL) compared with controls (P<0.001). In contrast, sVCAM-1 and E-selectin did not differ between the groups. Initiation of ART resulted in significantly lower levels of E-selectin (15.1+/-0.8; P<0.01), sICAM-1 (248+/-12 ng/mL; P<0.05), sVCAM-1 (766+/-33 ng/mL; P<0.001) and hsCRP (14 708+/-2358 ng/mL; P<0.001) after 2 months, which remained reduced at 14 months. tPAI-1 was not influenced by initiation of ART. CONCLUSIONS: Markers of endothelial dysfunction were elevated in treatment-naïve HIV-infected patients and were related to HIV RNA viral load. Initiation of ART reduced the levels of the majority of these markers. The positive effect of ART initiation was dependent on the duration of HIV infection prior to treatment.

Right and left cardiac function in HIV-infected patients investigated using radionuclide ventriculography and brain natriuretic peptide: a 5-year follow-up study.

OBJECTIVE: The aim of the study was to determine the incidence of myocardial dysfunction in an HIV-infected population receiving state-of-the-art treatment. METHODS: Between April 2001 and July 2002, 91 HIV-infected patients had a radionuclide ventriculography performed with determination of right ventricular ejection fraction (RVEF) and left ventricular ejection fraction (LVEF), as well as measurement of brain natriuretic peptide (BNP). Between July 2005 and January 2007, 63 patients (69%) agreed to participate in a follow-up study with a mean follow-up of 4.5 years. RESULTS: All patients had normal LVEF at both examinations. A minimal increase in mean LVEF of 0.02 was observed at follow-up (P=0.01). At the initial visit, four patients [6%; 95% confidence interval (CI) 2-15%] had a reduced RVEF, and at follow-up two patients (3%; 95% CI 0-11%) had slightly reduced RVEF. No significant change in mean RVEF was found. No patients had increased BNP and no change in mean plasma BNP was found. CONCLUSIONS: HIV-related cardiomyopathy appears not to constitute a problem in closely monitored, well-treated HIV-infected patients. Compared with pre-highly active antiretroviral therapy (HAART) studies, it seems that the improvement in immunocompetency and viral load has removed the problem of HIV-related cardiomyopathy. Although HAART has been suggested as a possible new cause of cardiomyopathy, we did not find any evidence of this.

[Leukocyte scintigraphy: indications and diagnostic value]. / Leukocytscintigrafi: indikation og diagnostisk vaerdi.

Leukocyte scintigraphy is a diagnostic method that allows visualisation of pathological accumulation of leukocytes. Some important indications are reviewed with special emphasis on the diagnostic value and possible limitations. Leukocyte scintigraphy is valuable for diagnosing osteomyelitis in bones with a pre-existing pathology, but probably not in chronic or vertebral osteomyelitis. The test is also valuable for detection of intra-abdominal abscess and vascular graft infection. Fever of unknown origin represents a diagnostic challenge. Although the sensitivity of leukocyte scintigraphy is only modest in this context, it seems to be a valuable addition to other tests performed in these patients.

Diagnostic value of PCR for detection of Borrelia burgdorferi DNA in clinical specimens from patients with erythema migrans and Lyme neuroborreliosis.

BACKGROUND: The aim of the study is to evaluate the diagnostic sensitivity of a 16S ribosomal RNA-based PCR on clinical specimens from patients with erythema migrans (EM) and neuroborreliosis and to compare the sensitivities with those obtained by in vitro culture and serological testing. A semiquantitative detection system, representing the input amount of specific DNA and thus the density of spirochetes in clinical specimens, indicated the preferred clinical sample to obtain for PCR testing. METHODS AND RESULTS: Skin biopsy and urine samples from 31 patients with EM and cerebrospinal fluid (CSF) and urine samples from 30 patients with neuroborreliosis were investigated. Borrelia burgdorferi DNA was detected in 71% of the skin biopsy specimens and 13% of the urine samples from patients with EM. Forty-one percent of the patients with EM were found to have B burgdorferi-specific antibodies in serum, and B burgdorferi was cultured in 29% of the EM specimens. For patients with neuroborreliosis, the diagnostic sensitivities in CSF and urine samples were 17% and 7%, respectively. Specific intrathecal antibody production was found in 90% of the patients, and 87% showed elevated B burgdorferi antibodies in serum. In general, PCR of skin biopsy samples yielded very high amounts of amplicons versus low amounts for CSF and urine samples. CONCLUSIONS: PCR of skin biopsy specimens is currently the most sensitive and specific test for the diagnosis of patients with EM, superior to culture and serological testing. For B burgdorferi-specific CSF disgnosis in patients with neuroborreliosis, the measurement of specific intrathecal antibody synthesis is superior to PCR. However, in patients with a short duration of disease (<14 days), PCR may be a useful diagnostic supplement. PCR of urine samples cannot be recommended at the present time for routine diagnosis of patients with EM or neuroborreliosis.

Long-term serological follow-up of patients treated for chronic cutaneous borreliosis or culture-positive erythema migrans.

The kinetics of antibodies to Borrelia burgdorferi following successful treatment of early and late cutaneous borreliosis were analysed in consecutive serum samples by an enzyme-linked immunosorbent assay (ELISA) technique. Twenty-three patients with culture positive erythema migrans were followed for 23+/-14 months: 41% stayed seronegative, 35% showed an isolated immunoglobulin M (IgM) response, 8% an isolated IgG response and 16% a combined IgM and IgG responses. In general, antibody levels peaked within the first 3 months of symptom onset, whereafter a gradual decline was observed within 1 year. Twenty-two patients with chronic cutaneous borreliosis were followed for 23+/-11 months and all patients stayed IgG positive. Nearly three-quarters showed a clear decline in IgG levels over the years, while the rest did not. After 9+/-1 years 88% of 16 patients examined were still IgG positive. In conclusion, treatment of erythema migrans should be initiated on clinical appearance as a substantial number of patients stayed seronegative. Treatment success may in part be monitored serologically for both seropositive erythema migrans and chronic cutaneous borreliosis as most patients show declining titres after successful treatment. However, continuously high titres do not necessarily indicate treatment failure.

Preoperative bone mineral density of the proximal tibia and migration of the tibial component after uncemented total knee arthroplasty.

Twenty-two patients with primary osteoarthrosis of the knee all operated on with insertion of an uncemented total knee arthroplasty had a preoperative measurement of bone mineral density (BMD) in the coronal plane of the proximal tibia performed by dual-photon absorptiometry. Postoperatively and with follow-up after 6 weeks (n = 21), 1 year (n = 22), and 3 years (n = 19), radiographs suitable for radiostereometric analysis of the tibial component migration were obtained. One year postoperatively, stress examinations were performed with the aim of measuring inducible displacement of the tibial component. Most of the migration, expressed as maximal total point motion (MTPM), occurred during the first year with an average migration of approximately 1 mm. Regression analysis showed a positive relation between BMD and MTPM after 6 weeks (P = .03, r = .47), 1 year (P = .0005, r = .68), and 3 years (P = .02, r = .54). Inducible displacement did not reveal any significant relation to BMD. MTPM between 1 and 3 years, which is the clinically most important parameter with respect to later loosening of the tibial component, showed a negative relation to BMD (P = .04, r = -.47). Thus, tibial components of knees with preoperative high tibial BMD showed less continuous migration.

Immunoserologic evidence of Human Granulocytic Ehrlichiosis in Danish patients with Lyme neuroborreliosis.

Human Granulocytic Ehrlichiosis (HGE) is a recently described human illness in the US which manifests as fever, myalgia and headache combined with pancytopenia and elevated concentrations of hepatic transaminases. Genetic analyses indicate that the agent of HGE appears to be an Ehrlichia species that is closely related to E. equi and E. phagocytophila. Ixodes dammini and I. scapularis were identified as potential vectors of HGE. Ixodes ticks are also the vector of Borrelia burgdorferi, the agent of Lyme borreliosis. The presence of antibodies against Ehrlichia in 132 sera from Danish patients with definite Lyme neuroborreliosis were examined in order to provide immunoserologic evidence of this infection in Denmark. Patients with Lyme neuroborreliosis were chosen as a test cohort, as these patients had been infested by a tick sufficient for transmission of B. burgdorferi. All had cerebrospinal fluid lymphocytic pleocytosis. As controls, serum samples from 50 healthy Danish blood donors were included. Of the 132 patients with Lyme neuroborreliosis, 5 (3.8%) reacted with the E. equi antigen substrate at titres 1:128. None of the blood donors were found seropositive for E. equi. At least 2 of the patients found seropositive for HGE constituted probable cases of HGE with E. equi antibody titres of at least 80 combined with fever, headache and myalgias. However, in no cases were we able to detect the presence of the HGE agent in the serum by PCR. We conclude that human exposure to granulocytic Ehrlichiae species may also occur in Europe, although further studies will be necessary to document active infection with these potential pathogens.

Roentgen stereophotogrammetric analysis using computer-based image-analysis.

The two-dimensional position of markers in radiographs for Roentgen Stereophotogrammetric Analysis (RSA) is usually determined using a measuring table. The purpose of this study was to evaluate the reproducibility and the accuracy of a new RSA system using digitized radiographs and image-processing algorithms to determine the marker position in the radiographs. Four double-RSA examinations of a phantom and 18 RSA examinations from six patients included in different RSA-studies of knee prostheses were used to test the reproducibility and the accuracy of the system. The radiographs were scanned at 600 dpi resolution and 256 gray levels. The center of each of the tantalum-markers in the radiographs was calculated by the computer program from the contour of the marker with the use of an edge-detection software algorithm after the marker was identified on a PC monitor. The study showed that computer-based image analysis can be used in RSA-examinations. The advantages of using image-processing software in RSA are that the marker positions are determined in an objective manner, and that there is no need for a systematic manual identification of all the markers on the radiograph before the actual measurement.