Börje Åkerlund

Increased production of malondialdehyde in patients with HIV infection

The mean plasma content of malondialdehyde (MDA) in 30 patients in different stages of HIV infection was found to be about 30% higher than that in controls. The phenomenon was not correlated to the degree of immunodeficiency and was noted early in the course of the disease. This indicates a higher degree of basal lipid peroxidation, which might contribute to the tissue damage seen in these patients. A new reverse phase liquid chromatography method was used for quantitative measurements of MDA in plasma after reaction of this compound with thiobarbituric acid.

Dyslipoproteinemia in Patients with Severe Bacterial Infections

Infection induces changes in the serum lipoprotein pattern in man. In this report the concentration of cholesterol and triglycerides in the major serum lipoprotein classes were followed in 9 patients with severe bacterial infections. Blood samples for lipoprotein analysis were obtained in the fasting state the first 4 days after admission to the hospital and after 2-3 weeks and 2 months. The serum lipoprotein concentrations of the patients were compared with those from a group of healthy subjects. The total serum cholesterol concentration was lowered during the acute stage of the disease and remained low the first days in hospital. The very low (VLDL) density lipoprotein cholesterol level in serum was mainly within the normal range. The low (LDL) density lipoprotein cholesterol values in serum were low during the first 4 days in hospital. The high (HDL) density lipoprotein cholesterol concentration values were extremely decreased on the first day in hospital and had a tendency to further reduction from day 1 to day 4. Both the LDL and the HDL serum cholesterol were normalized after recovery.

Oxygen radical release by neutrophils of HIV-infected patients

Neutrophils from asymptomatic HIV-infected patients have an increased Nitroblue tetrazolium (NBT) reduction, that is an increased production of oxygen radicals. Plasma from these patients can activate normal neutrophils to an increased NBT-reduction and the neutrophil activating factor thus seems to be mainly plasma bound. Further, the patients also have increased levels of plasma malondialdehyde and thus an increased lipid peroxidation. Plasma cysteine levels are low, a sign of increased consumption of antioxidants. Treatment of the asymptomatic HIV-infected patients with N-acetylcysteine corrected the plasma cysteine levels and had some beneficial effects, but did not inhibit the increased radical production by the neutrophils.

Glutathione and HIV infection

Dr Buhl and colleagues (Dec 2, p 1294) report significant reductions in systemic glutathione concentrations in symptomless HIV seropositive individuals and suggest that this may be important in the immune dysfunction of HIV infection. They measured glutathione in venous plasma and in bronchial epithelial lining fluid and found reductions of 30% and 60%, respectively, in 14 HIV seropositive patients compared with 19 controls

The Effect of Antiretroviral Combination Treatment on Epstein-Barr Virus (EBV) Genome Load in HIV-Infected Patients

We evaluated the effect of combination anti-retroviral treatment (cART) on the host control of EBV infection in moderately immunosuppressed HIV-1 patients. Twenty HIV-1 infected individuals were followed for five years with repeated measurements of EBV DNA load in peripheral blood lymphocytes in relation to HIV-RNA titers and CD4+ cell counts. Individuals with optimal response, i.e. durable non-detectable HIV-RNA, showed a decline of EBV load to the level of healthy controls. Individuals with non-optimal HIV-1 control did not restore their EBV control. Long-lasting suppression of HIV-replication after early initiation of cART is a prerequisite for re-establishing the immune control of EBV.

Epstein Barr virus DNA analysis in blood predicts disease progression in a rare case of plasmablastic lymphoma with effusion

BackgroundIn HIV-1-infected patients a long lasting CD4+ cell decline influences the host-EBV balance and thereby increases the risk for EBV related malignancies. In spite of a world-wide access to combination antiretroviral therapy (cART) there are still a considerable number of HIV-1-infected patients who will develop severe immunodeficiency. These undiagnosed HIV-1 infected patients, so called late testers, demonstrate an increased lymphoma risk, compared to patients diagnosed early. Consecutive individual screening for EBV DNA-load in late testers might be a useful predictor of emerging EBV-malignancy.MethodsPatient biopsies and ascites were analyzed morphologically, by immuncyto-histochemistry and in-situ hybridization. Viral DNA and RNA load were quantified by PCR. Cell lines from primary tumor and from ascites, were established in vitro and further analyzed.ResultWe here report on a case of EBV-positive lymphoma in an AIDS patient, first presenting with pleural effusion and ascites and was thus initially considered a primary effusion lymphoma (PEL) but was later diagnosed as a plasmablastic lymphoma (PBL). The patient had responded to cART with undetectable HIV-RNA and increased CD4 cell count one year prior to lymphoma presentation. At the time of lymphoma diagnosis the HIV-RNA values were <50 RNA-copies per mL blood (undetectable) and the CD4-positive cell count 170 ×106/L. The lymphoma was CD45-negative and weakly CD22- and CD30-positive. The patient had a history of Kaposi sarcoma and HHV-8 seropositivity. The lymphoma biopsies, and three cell lines derived on different occasions from the tumor cell effusion, were all EBV-positive but HHV-8 negative.A noticeable EBV-DNA load decline was observed during the remission of the lymphoma following CHOP-therapy. The EBV-DNA load increased dramatically at the time of recurrence.ConclusionEBV DNA load might be useful in monitoring the effect of lymphoma treatment as well as in estimating the risk of EBV-associated lymphoma in HIV-1 infected patients with pronounced immunosuppression.

Increased risk of abdominal wall hernia associated with combination anti-retroviral therapy in HIV-infected patients-results from a Swedish cohort-study.

To determine if anti‐retroviral therapy (ART) in HIV‐infected patients is associated with an increased risk for development of abdominal wall hernia.

Host-Epstein-Barr virus relationship affected by immunostimulation in HIV-infected patients representing distinct progressor profile groups.

Abstract Background: Human immunodeficiency virus (HIV) infection with pronounced immunosuppression disrupts Epstein–Barr virus (EBV)–host balance with increased lymphoma risk. We explored whether different host responses to HIV are reflected in the EBV–host balance. Methods: Eleven unvaccinated HIV-positive patients and 16 participants in a vaccine trial were included in the study. Blood samples were collected, B cells extracted, and EBV DNA load was determined using a semiquantitative polymerase chain reaction (PCR) method. Results: Treatment-naïve patients with a history of symptomatic primary HIV infection showed non-significant, but higher EBV load compared to untreated long-term non-progressors. A significant difference in HIV RNA titres between these groups correlated weakly to EBV DNA load. Patients in the vaccine trial with recombinant HIV gp160 and/or adjuvant and with a history of symptomatic primary HIV infection, showed a 1-log increase in EBV load compared to patients with long-lasting HIV disease. Conclusion: Different host responses to HIV infection, especially in combination with vaccination, can be reflected in the EBV–host balance.

Diabetic osteoarthropathy care in Sweden – Need for improvement: A national inventory

Highlights • 79% of the clinics had no guidelines for managing patients with osteoarthropathy.• Only two clinics presented acceptable guidelines.• Plain X-ray, was the common diagnostic method.

Fulminant anaplastic large cell lymphoma (ALCL) concomitant with primary cytomegalovirus (CMV) infection, and human herpes virus 8 (HHV-8) infection together with Epstein-Barr-virus (EBV) reactivation in a patient with asymptomatic HIV-infection

BackgroundMost malignant lymphomas in HIV-patients are caused by reactivation of EBV-infection. Some lymphomas have a very rapid fulminant course. HHV-8 has also been reported to be a cause of lymphoma. The role of CMV in the development of lymphoma is not clear, though both CMV and HHV-8 have been reported in tissues adjacent to the tumour in Burkitt lymphoma patients. Here we present a patient with asymptomatic HIV infection, that contracted a primary cytomegalovirus (CMV) infection and human herpes virus 8 (HHV-8) infection. Three weeks before onset of symptoms the patient had unprotected sex which could be possible source of his CMV and also HHV-8 infection He deteriorated rapidly and died with a generalized anaplastic large cell lymphoma (ALCL).MethodsA Caucasian homosexual male with asymptomatic human immunodeficiency virus (HIV) infection contracted a primary cytomegalovirus (CMV) infection and human herpes virus 8 (HHV-8) infection. He deteriorated rapidly and died with a generalized anaplastic large cell lymphoma (ALCL). Clinical and laboratory records were compiled. Immunohistochemistry was performed on lymphoid tissues, a liver biopsy, a bone marrow aspirate and the spleen during the illness and at autopsy. Serology and PCR for HIV, CMV, EBV, HHV-1–3 and 6–8 was performed on blood drawn during the course of disease.ResultsThe patient presented with an acute primary CMV infection. Biopsies taken 2 weeks before death showed a small focus of ALCL in one lymph node of the neck. Autopsy demonstrated a massive infiltration of ALCL in lymph nodes, liver, spleen and bone marrow. Blood samples confirmed primary CMV- infection, a HHV-8 infection together with reactivation of Epstein- Barr-virus (EBV).ConclusionPrimary CMV-infection and concomitant HHV-8 infection correlated with reactivation of EBV. We propose that these two viruses influenced the development and progression of the lymphoma. Quantitative PCR blood analysis for EBV, CMV and HHV-8 could be valuable in diagnosis and treatment of this type of very rapidly developing lymphoma. It is also a reminder of the importance of prevention and prophylaxis of several infections by having protected sex.