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Biomedical subjects

L Mathiesen

Publications and source records attributed to L Mathiesen.

At least 37 records · Page 2Linked to original sources
PubMed1994

Detection of cytomegalovirus DNA in serum correlates with clinical cytomegalovirus retinitis in AIDS.

The high sensitivity of nested polymerase chain reaction (PCR) offers the possibility of rapid detection of cytomegalovirus (CMV) DNA in serum. Five consecutive serum samples were examined from 52 human immunodeficiency virus (HIV)-seropositive patients (19 of whom had clinically presumed diagnosis of CMV chorioretinitis). Presence of CMV DNA in serum was shown to precede development of clinical disease. Eleven patients who developed chorioretinitis were positive for CMV DNA in serum samples obtained 3 months before clinical disease, and 3 retinitis patients who initially were negative for CMV DNA became positive with the onset of clinical retinitis. In contrast, 29 of 33 HIV-seropositive subjects without clinical CMV chorioretinitis and matched with respect to age and CD4 T cell numbers were negative for CMV DNA in all 5 serum samples. Thus, the presence of CMV DNA in serum analyzed by PCR is a good predictive marker of CMV retinitis in HIV-seropositive subjects. A positive PCR results supports the clinical diagnosis and may be useful for monitoring response to antiviral treatment.

AIDS-Related Opportunistic Infections↗
PubMed1994

Zidovudine twice daily in asymptomatic subjects with HIV infection and a high risk of progression to AIDS: a randomized, double-blind placebo-controlled study. The European-Australian Collaborative Group (Study 017)

OBJECTIVE: To evaluate the efficacy of zidovudine given twice daily in subjects with asymptomatic HIV-1 infection and a high risk of progression to AIDS. DESIGN: Randomized, double-blind placebo-controlled trial. SETTING: Multicentre study in five European countries and Australia. PATIENTS: Asymptomatic subjects (n = 329) with CD4 cell counts between 200 and 400 x 10(6)/l, or if > 400 x 10(6)/l, subjects with HIV p24 antigenaemia (> 10 pg/ml). INTERVENTION: Patients were randomly assigned to receive zidovudine 500 mg or placebo twice daily for 104 weeks, following a 250 mg four times daily dose regimen for the first 4 weeks. MAIN OUTCOME MEASURES: The primary end-point was the development of AIDS or severe AIDS-related complex (ARC). Before unblinding the study other end-points were defined: the development of Centers for Disease Control and Prevention (CDC) group IV disease (AIDS, severe ARC and other CDC stage IV disease) and the development of symptomatic HIV disease (AIDS, severe ARC, other CDC stage IV disease and minor HIV disease). Changes in CD4+ cell counts, p24 antigenaemia and toxicity were also reviewed. RESULTS: Median treatment duration was 57 weeks for the placebo and 60 weeks for the zidovudine group, respectively. Progression to AIDS or severe ARC occurred in 17 placebo and 12 zidovudine recipients (log-rank P = 0.26). However, in the first of the 2 study years the rate of progression to AIDS or severe ARC was significantly higher in the placebo than in the zidovudine group. Zidovudine delayed progression to symptomatic HIV disease (P = 0.01); a trend in a delay in progression to CDC stage IV disease was observed (P = 0.08). Zidovudine recipients maintained CD4+ cell counts at or above baseline levels for longer than placebo recipients (P = 0.04). HIV p24-antigen levels decreased in the zidovudine group and returned to pretreatment levels by week 36. Substantial toxicity was not observed. CONCLUSIONS: Zidovudine twice daily is effective in delaying progression to symptomatic HIV disease in high-risk, asymptomatic HIV-infected subjects. Modified definitions of clinical end-points may be useful for evaluating Phase III trials in comparable patient groups in the light of changes in the definition of AIDS and the increasing use of primary prophylaxis against opportunistic infections.

AIDS-Related Complex↗
PubMed1993

Atypical varicella-zoster infection in AIDS.

A case of atypical varicella zoster in a 33-year-old AIDS patient is reported. The patient had had two attacks of herpes zoster within a year and was given high-dose acyclovir several times. Thereafter he developed small keratotic pellucid papules on fingers, wrists and face, which were found to contain varicella-zoster antigen by the ELISA test. Skin biopsy showed acanthosis and lack of vesication, as is usually seen in herpes infections. The atypical varicella-like lesions persisted despite repeated doses of acyclovir but cleared temporarily when the patient was given foscarnet. We believe that the prolonged therapy may have allowed selection of acyclovir-resistant varicella-zoster strains, resulting in the atypical clinical course.

Acquired Immunodeficiency Syndrome↗
PubMed1993

IgM response to a human Pneumocystis carinii surface antigen in HIV-infected patients with pulmonary symptoms.

We have developed an ELISA to detect IgM antibodies to a major human Pneumocystis carinii surface antigen (gp95), and investigated the IgM response in 128 HIV-infected patients who underwent bronchoscopy for evaluation of pulmonary symptoms. Only 5 (4%) patients had IgM antibodies to P. carinii gp95. Four of the 5 patients with IgM antibodies also had IgG antibodies to gp95 and microbiologically proven P. carinii pneumonia (PCP). In 76/128 patients for whom serial samples were available, changes in antibody response were determined. In 3 patients we demonstrated an increase in IgM antibody response to gp95. These patients also showed an increase in IgG antibodies to gp95 and had microbiologically proven PCP. Prior to the development of the IgM response, IgG antibodies to gp95 were detectable in all 3 patients. Thus, HIV-infected patients with PCP seldom produce IgM antibodies to the major human P. carinii surface antigen. The increase in IgM response during the course of PCP observed in 3 patients suggests either reinfection with a new strain, or antigenic drift of an already acquired strain of P. carinii.

AIDS-Related Opportunistic Infections↗
PubMed1993

Extra-intestinal amebiasis: clinical presentation in a non-endemic setting.

37/38 patients with reciprocal titers > or = 512 against Entamoeba histolytica in Denmark over a 5-year period were evaluated retrospectively in order to establish the clinical profile of extra-intestinal amebiasis in a non-endemic area. 24 of these had extra-intestinal amebiasis, all presenting 1 or more amebic liver abscesses on ultrasonography. Fever was the most common finding, present in 91% of the cases. The most striking observation was the lack of both abdominal pain and tenderness in 22% of the patients with liver abscess. Pulmonary symptoms and abnormal chest X-rays were each recorded in 45% of the cases. Liver abscesses with or without pulmonary involvement were the only extra-intestinal manifestations recorded. The condition was initially misconceived in more than half the cases, but most of the patients responded well once treatment with metronidazole was started.

Adult↗
PubMed1993

Aerosolized pentamidine for primary prophylaxis of Pneumocystis carinii pneumonia: a controlled, randomized trial.

The objective was to assess the efficacy of a biweekly dose of 60 mg aerosolized pentamidine (AP) for primary prophylaxis (PP) of Pneumocystis carinii pneumonia (PCP) and the impact of prophylaxis on survival in HIV-infected patients. Participants were AIDS patients with no history of PCP, patients with a CD4 count < or = 0.200 x 10(9)/L, or patients belonging to the CDC group IVC2, irrespective of CD4 count. It was an open, randomized, controlled trial. Patients were assigned to receive AP, 60 mg biweekly via a System 22 nebulizer, or to a control group not receiving any prophylaxis. Incidence curves for PCP and survival were generated using the Kaplan-Meier method, stratified by treatment group, and compared using the log-rank test. Data were analyzed according to intention to treat. There were 15 cases of PCP among 105 patients in the AP group and 32 cases among 104 patients in the control group. The cumulative incidence of PCP by 18 months was 13% (95% CI 5-21%) in the AP group and 30% (95% CI 18-41%) in the control group, (p = 0.002). During the study period 19 patients (18%) in the AP group died and 24 patients (23%) in the control group (NS; p = 0.28). We conclude that a biweekly dose of 60 mg AP is efficient as primary PCP prophylaxis when a System 22 nebulizer is used. There was, however, no difference in survival between the groups, suggesting that AP has an impact on morbidity only.

AIDS-Related Opportunistic Infections↗
PubMed1993

Glycosylation of the major human Pneumocystis carinii surface antigen.

It has recently been shown that the major rat P. carinii surface antigen is important for initial host-organism attachment, possibly through binding to fibronectin, mannose-binding protein, or surfactant protein A. Since a carbohydrate/lectin interaction may be involved in adhesion, we undertook this study to characterize the glycosylation of the major human P. carinii surface glycoprotein (gp95). We have used purified gp95 as a source of antigen, and in lectin binding and deglycosylation studies it was found that approximately 9% of gp95 consists of N-linked carbohydrates of mainly high-mannose and bisected complex-type glycans. Using a polyclonal antibody raised against purified gp95 and crossed affinoimmunoelectrophoresis and the lectins Con A and WGA, gp95 exhibited carbohydrate-dependent microheterogeneity. We therefore suggest that gp95 is composed of subtypes which differ in N-linked glycosylation.

Antigens, Fungal↗
PubMed1992

Antibody responses to a major Pneumocystis carinii antigen in human immunodeficiency virus-infected patients with and without P. carinii pneumonia.

Antibody responses to a major purified human Pneumocystis carinii surface antigen (gp95) were determined by ELISA in human immunodeficiency virus (HIV)-infected patients. Serum IgG directed against gp95 was measured in 129 consecutive HIV-infected patients who underwent bronchoscopy for evaluation of pulmonary symptoms. Significantly more patients with P. carinii pneumonia (PCP) had detectable antibodies compared with HIV-infected patients without PCP and with HIV-negative controls (50 [66%] of 76 vs. 18 [34%] of 53 and 7 [35%] of 20, respectively; P less than .001), and the level of antibody response was higher (mean optical density ratio: 0.6 vs. 0.23 and 0.2, respectively; P less than .01). Changes in antibody response were investigated in 78 patients for whom serial serum samples taken around the time of bronchoscopy were available. Of the 47 patients with verified PCP, 20 (43%) mounted an antibody response, compared with only 1 (3%) of 31 patients without PCP (P less than .001). This patient had PCP on the basis of clinical criteria, including response to therapy. Thus, despite severe immunosuppression, a proportion of HIV-infected patients with PCP can mount a specific IgG-mediated antibody response to P. carinii.

Antibodies, Fungal↗
PubMed1992

Impact of the 1987 revised AIDS case definition in Denmark: a follow-up study 2 years after its adoption.

We present a follow-up study on Danish AIDS patients notified according to the latest revision of the AIDS case definition during the first 2 years after its adoption. A total of 271 adult AIDS cases were notified in the period of study (Jan. 1, 1988-Dec. 31, 1989). 60 patients (22%) met only the revised AIDS case definition and of these 17 patients (28%) developed diseases meeting the old AIDS case definition. Thus, AIDS reporting increased by 28% due to the change in case definition, the impact being 19% after adjusting for patients developing old case diseases. No time trend in the impact was found. We estimated the cumulative percent of cases meeting the new case definition who subsequently will develop diseases meeting the old definition as 15% after 6 months and 51% after 18 months. The revision produced a disproportionate increase in reporting of female cases (p less than 0.05), transfusion cases (p less than 0.01) and to a lesser extent of heterosexual cases, while the impact on reporting of homo/bisexual men showed a decrease (p less than 0.01). Cases notified with new case definition diseases were older than cases notified with old diseases. Among patients meeting only the new case definition, 25 died and 18 (30%) had not developed old case diseases before death. We found no difference in survival rates between patients within the 2 groups of case definition. Among patients meeting the new definition we found no differences in HIV antigenemia or CD4 cell count between those developing diseases meeting old case definition and those who did not.

Acquired Immunodeficiency Syndrome↗
PubMed1992

Autologous HIV-1 neutralizing antibodies: emergence of neutralization-resistant escape virus and subsequent development of escape virus neutralizing antibodies.

The capacity of consecutive human sera to neutralize sequentially obtained autologous virus isolates was studied. HIV-1 was isolated three times over a 48-164-week period from three individuals immediately after seroconversion and from two individuals in later stages of infection. Development of neutralizing antibodies to the primary virus isolates was detected 13-45 weeks after seroconversion. Emergence of escape virus with reduced sensitivity to neutralization by autologous sera was demonstrated. The patients subsequently developed neutralizing antibodies against the escape virus but after a delay. Titers of neutralizing antibodies against late virus isolates were generally low compared to initial neutralizing titers against primary virus isolates. The delay in appearance of neutralizing antibodies to the dominant viral strain at any time in the patient and the emergence of neutralization resistant escape virus may be part of the explanation of the apparent failure of the immune system to control HIV infection.

HIV Antibodies↗
PubMed1991

A preliminary report on the neuropsychologic sequelae of human immunodeficiency virus.

The neuropsychologic sequelae of acquired immunodeficiency syndrome and human immunodeficiency virus were studied by comparing the results of a neuropsychologic test battery administered to the following three groups of Danish homosexual men: 20 patients with acquired immunodeficiency syndrome, 20 asymptomatic subjects who tested positive for the human immunodeficiency virus, and a matched control group of 20 subjects who tested negative for the human immunodeficiency virus. The group with acquired immunodeficiency syndrome performed significantly worse than the control subjects on the tests measuring concentration, memory, and psychomotor speed. The group with human immunodeficiency virus performed significantly worse than the control subjects on the tests measuring verbal memory and psychomotor speed. On the other tests, their results varied. The study supports the hypothesis that not only patients with acquired immunodeficiency syndrome but also asymptomatic subjects with human immunodeficiency virus may be neuropsychologically impaired early in the course of the disease.

AIDS Dementia Complex↗
PubMed1991

Broadly neutralizing antibodies targeted to mucin-type carbohydrate epitopes of human immunodeficiency virus.

The cancer-related mucin-type carbohydrate neoantigen Tn was found on gp160 and gp120 of human immunodeficiency virus (HIV). Immunoglobulin G (IgG) and IgM monoclonal antibodies (MAbs) against Tn neutralized infection with cell-free virus and blocked fusion between HIV-infected and uninfected cells. This inhibition was found in infection of both lymphocytic cells and monocytoid cells. Viruses tested included six HIV-1 and five HIV-2 isolates propagated in different cells, as well as infectious plasma from AIDS patients. The antiviral effect of anti-Tn MAbs occurred by specific binding of the MAb to the virus; this binding was inhibitable by pure Tn antigen, and indications were found that this inhibition occurred at a pre-entry step. Boosting the naturally occurring low-titer anti-Tn activity may be of prophylactic value, as suggested by the in vitro neutralization found in this study.

Antibodies, Monoclonal↗
PubMed1991

Chronic evolution of acute hepatitis B: the significance of simultaneous infections with hepatitis C and D. Copenhagen Hepatitis Acuta Programme.

Seventy-six of 77 consecutive patients with hepatitis B surface antigen (HBsAg)-positive acute hepatitis were reevaluated using anti-hepatitis C virus (HCV), anti-hepatitis D virus (HDV), and IgM anti-hepatitis B core (HBc) testing. Anti-HCV and/or anti-HDV was found in 32 patients (42%). The presence of these markers was significantly associated with intravenous drug abuse (p less than 10(-6). Sixty-nine patients were IgM anti-HBc-positive, of whom two (3%) (95% confidence limits, 1-12%) became chronic HBsAg carriers with histologically verified chronic liver disease; both were anti-HCV and anti-HDV-negative. Among the remaining 67 IgM anti-HBc-positive patients 8 had HBV and HDV co-infection, 3 had HBV and HCV co-infection, and 1 had HBV, HCV, and HDV co-infection. Twenty-two had evidence of preceding or past HCV infection; two developed chronic active hepatitis in spite of HBsAg clearance. Seven patients with IgM anti-HBc negative. One was a chronic HBsAg carrier with HDV superinfection. One had subclinical acute HBV infection and became a chronic HBsAg carrier. In a further two patients reactivation of replication in a chronic HBV infection could not be disregarded. Three patients could not be classified; all had acute recent onset of symptoms, cleared HBsAg within 6 months, but lacked IgM anti-HBc. It is concluded that HCV and HDV superinfections in HBV carriers mimicking acute HBV infection with chronic evolution are rarely encountered in the present population in spite of high frequency of both HCV and HDV markers.

Adolescent↗
PubMed1991

The outcome of mechanical ventilation in patients with an AIDS-associated primary episode of Pneumocystis carinii pneumonia.

The justification for mechanical ventilation (MV) of patients with an AIDS-related Pneumocystis carinii pneumonia (PCP) has been submitted to debate, due to poor prognosis of AIDS patients. Since the start of the epidemic our policy has been to offer MV to this group of patients when needed. The first 28 patients who received MV because of an AIDS-related primary episode of PCP were reviewed (28/126 patients; 22%). 14 of these patients were discharged from hospital. Their median survival time was 20.5 (range 7.8-37.1) months, dated from the episode. Life table analysis of these patients and patients with a less severe primary episode of AIDS-related PCP treated in the same period, did not reveal any difference in long-term survival. We were not able to demonstrate any prognostic factor separating MV patients who survived from those who died. On the basis of these results we recommend that MV is offered to all patients with a life threatening AIDS-associated primary episode of PCP.

Acquired Immunodeficiency Syndrome↗
PubMed1991

Cerebral toxoplasmosis in Danish AIDS patients.

We estimate the frequency of central nervous system (CNS) toxoplasmosis in Danish AIDS patients and evaluate the diagnostic accuracy using the following criteria for acceptance of the diagnosis: either (1) the demonstration of Toxoplasma gondii in brain tissue or (2) one or more hypodense or ring-enhancing lesions on computerized axial tomography (CAT) scan and a neurologic and CAT scan improvement in response to 2 weeks of treatment. From 1981 until July 1990 266 patients were diagnosed with AIDS at Hvidovre Hospital, Copenhagen and 29 (11%) were treated, suspected for CNS toxoplasmosis. 17 patients had the diagnosis confirmed but since 5 patients, who were never treated, were diagnosed at autopsy, the overall cumulated incidence was 8% (22/266 patients). The overall diagnostic accuracy was 59% (17/29 patients) showing some changes over time. Among patients diagnosed with AIDS in 1988 or later, the accuracy was 83% (10/12 patients) while among patients diagnosed in 1987 or earlier the accuracy was 41% (7/17 patients). Four patients were diagnosed with Pneumocystis carinii pneumonia (PCP) prior to the diagnosis of CNS toxoplasmosis, while among patients with toxoplasmosis as the AIDS-defining diagnosis, 3 later developed PCP. None of these 7 patients had received secondary prophylaxis with a drug containing sulfonamide.

Acquired Immunodeficiency Syndrome↗
PubMed1991

Ranitidine improves certain cellular immune responses in asymptomatic HIV-infected individuals.

Human immunodeficiency virus (HIV) infection is characterized by a progressive impairment in immunocompetence leading to severe opportunistic infections and malignancies. In a double-blind, placebo-controlled study, the potential impact of immunomodulation by oral ranitidine, 600 mg daily, for 28 days was studied in 18 HIV-positive patients (CDC group II). All were without clinical signs of infections and were not treated with other known immunomodulating agents. Several immunological parameters related to HIV infection were studied and confirmed to be impaired early in HIV infection. Spontaneous and in vitro interleukin-2- and interferon-alpha-stimulated natural killer cell activity improved in the ranitidine-treated patients in contrast to a decrease in nontreated patients (#p less than 0.03, #p less than 0.01, #p less than 0.02 between groups, respectively). Furthermore, T-cell blastogenesis to phytohemagglutinin stimulation and soluble interleukin-2 receptors in serum increased in ranitidine-treated patients compared with nontreated patients (#p less than 0.01). However, ranitidine treatment did not change CD4+ cell counts. Although the significant improvement in immunocompetence shown in this study is small, the present result indicates the need for further trials with immunomodulation by ranitidine in HIV-infected individuals.

Adult↗
PubMed1990

Inhibition of human immunodeficiency virus (HIV) infection in vitro by anticarbohydrate monoclonal antibodies: peripheral glycosylation of HIV envelope glycoprotein gp120 may be a target for virus neutralization.

Carbohydrate structures are often involved in the initial adhesion of pathogens to target cells. In the present study, a panel of anticarbohydrate monoclonal antibodies (MAbs) was tested for their ability to inhibit in vitro human immunodeficiency virus infectivity. MAbs against three different N- and O-linked carbohydrate epitopes (LeY, A1, and sialyl-Tn) were able to block infection by cell-free virus as well as inhibit syncytium formation. Inhibition of virus infectivity was independent of virus strain (HTLVIIIB or patient isolate SSI-002), the cell line used for virus propagation (H9 or MT4), and the cell type used as the infection target (MT4, PMC, or selected T4 lymphocytes). Inhibition was observed when viruses were preincubated with MAbs but not when cells were preincubated with MAbs before inoculation, and the MAbs were shown to precipitate 125I-labeled gp120. The MAbs therefore define carbohydrate structures expressed by the viral envelope glycoprotein gp120, indicating that glycans of the viral envelope are possible targets for immunotherapy or vaccine development or both.

Antibodies, Monoclonal↗