[Parasitologic diagnosis. Enterobius vermicularis].
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Albendazole↗
Biomedical subjects
C Pedersen
Publications and source records attributed to C Pedersen.
[Plasmodium falciparum malaria].
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Animals↗
[Mycobacterium avium complex infection in a patient with idiopathic CD4+ T-lymphocytopenia].
Primary cutaneous infections with MAC are extremely rare. We report a case of primary cutaneous infection with MAC, in a 69 year-old HIV-negative male. Idiopathic CD4+ T-lymphocytopenia was diagnosed.
Aged↗
Regional differences in presentation of AIDS in Europe.
Data were collected on 6578 patients diagnosed with AIDS at 52 clinical centres in 17 European countries during an 1-year period from 1979 to 1989. The centres were divided into four regions, North, Central, Southeast, and Southwest. Differences in the incidence of most AIDS-defining opportunistic infections and malignancies were found. After adjusting for known possible confounders, statistically significant differences between regions remained. Pneumocystis carinii pneumonia (PCP) was more common in Northern Europe, Kaposi's sarcoma and toxoplasmosis in Central Europe, cytomegalovirus retinitis in South-eastern Europe, and extrapulmonary tuberculosis in South-western Europe. These differences we attribute primarily to different degrees of exposure to the respective underlying pathogens. The prevalence of these and other micro-organisms will determine the clinical course of HIV infections in parts of Eastern Europe and elsewhere where the virus now is spreading.
AIDS-Related Opportunistic Infections↗
Transgenic Trifolium repens with foliage accumulating the high sulphur protein, sunflower seed albumin.
With the aim of increasing the rumen-protected level of the sulphur amino acids cysteine and methionine in Trifolium repens, we introduced the coding sequence of the sunflower seed albumin (SSA) into T. repens by Agrobacterium tumefaciens-mediated transformation. The SSA gene was modified such that the protein would be localised to the endoplasmic reticulum (ER). Four different T-DNA constructions all containing the SSA gene driven by either the promoter of a gene encoding the small subunit of ribulose bisphosphate carboxylase (Rubisco) from Arabidopsis thaliana (Assu), the promoter of the gene encoding the small subunit of Rubisco of Medicago sativa (Lssu), or the Cauliflower Mosaic Virus 35S promoter (CaMV35S), were transferred to T. repens cv. Haifa. Transgenic T0-plants and inter-transgenic hybrids were analysed for the level of SSA accumulation in the leaves by western blotting. The highest observed level of SSA accumulation was 0.1% of total extractable leaf protein. We observed that the promoter had a substantive effect on the level of SSA accumulation with Assu > CaMV35S > Lssu. Results from the inter-transgenic hybrids showed that the capacity to synthesise SSA was inherited. However the level of SSA accumulation in the leaves generally appears not to be additive with extra transgenic loci. During this work, we attempted to improve the efficiency of A. tumefaciens-mediated transformation of T. repens using the SAAT-method (Sonication Assisted Agrobacterium-mediated Transformation) on cotyledons of T. repens. T-DNA transfer was in general not enhanced by sonication compared to traditional A. tumefaciens-mediated transformation. Furthermore, Southern blot analyses of plants regenerated from the same cotyledon after A. tumefaciens treatment and under selection, indicated that multiple shoots were usually derived from the same transformation event. We concluded from these results that only one plant from each A. tumefaciens-treated cotyledon should be taken to avoid transgenic clones.
2S Albumins, Plant↗
Human immunodeficiency virus-associated malignant lymphoma in eastern Denmark diagnosed from 1990-1996: clinical features, histopathology, and association with Epstein-Barr virus and human herpesvirus-8.
The clinicopathological features of human immunodeficiency virus (HIV)-associated lymphoma were investigated in a retrospective study of 85 adult patients in eastern Denmark diagnosed during the period 1990-1996. The possible pathogenetic role of Epstein-Barr virus (EBV) and human herpesvirus 8 (HHV-8) in these tumours was also studied. Seventy patients (82%) presented with extranodal disease and 26 (31%) had CNS involvement at diagnosis. Diffuse large cell B-cell lymphoma was the most frequent histological subtype, comprising 65 of 79 cases available for microscopic re-evaluation (82%) and including 20 of 23 evaluable patients with CNS lymphoma (87%). EBV RNA was demonstrated by in situ hybridization in 51 of 65 evaluable tumours (79%) and in 14 of 16 cases (88%) with CNS-lymphoma. Three cases showed a T-cell phenotype. The presence of HHV-8 DNA was analysed by PCR in 32 cases. A strong band consistent with tumour cell infection was detected in only one case, weaker bands being seen in 4 cases. None of these patients had primary effusion lymphomas. In conclusion, Danish AIDS-related lymphomas are of predominantly high-grade B-cell type with extranodal localization and atypical presentation. Our results provide further evidence that EBV plays a major role in the pathogenesis of large cell AIDS-related lymphoma, whereas HHV-8 does not appear to contribute significantly to the development of solid lymphomas in this group of patients.
Adult↗
CNS infection with clostridium septicum.
We present an unusual case of Clostridium septicum brain infection in a 72-yr-old woman who had no underlying malignant disease. The infection spread from a localized sit to the CNS causing gas formation. The patient died rapidly.
Aged↗
Infections with Mycobacterium tuberculosis and Mycobacterium avium among HIV-infected patients after the introduction of highly active antiretroviral therapy. EuroSIDA Study Group JD.
The impact of highly active antiretroviral therapy (HAART) among human immunodeficiency virus (HIV)-infected patients on the incidences of mycobacterial infections has not been studied in detail. We assessed incidences of mycobacterial diseases among HIV- infected patients following the introduction of HAART, using data from the EuroSIDA study, a European, multicenter observational cohort of more than 7,000 patients. Overall incidences of Mycobacterium tuberculosis (TB) and Mycobacterium avium complex (MAC) were 0.8 and 1.4 cases/100 person-years of follow-up (PYF), decreasing from 1.8 (TB) and 3.5 cases/100 PYF (MAC) before September 1995 to 0.3 and 0.2 cases/100 PYF after March 1997. After adjustment for changes in CD4 cell count and use of antiretroviral treatment in Cox proportional hazards models, the risk of MAC decreased with increasing calendar time (hazard ratio per calendar year; HR = 0.58 [95% confidence intervals: 0.45-0.74], whereas this was not the case for TB; 0.95 [0.74-1.22]). In conclusion, we documented marked decreases in the incidence of TB and to an even larger extent of MAC among HIV-infected patients from 1994 to 1999. The decrease in TB was associated with the introduction of HAART and changes in CD4 cell count. These factors could also explain some of the decrease in MAC over time, though there remained a significantly lower risk of MAC than expected.
AIDS-Related Opportunistic Infections↗
Genotypic and phenotypic nevirapine resistance correlates with virological failure during salvage therapy including abacavir and nevirapine.
OBJECTIVE: To study the development of resistance during 8 weeks of salvage therapy with abacavir and nevirapine in combination with other reverse transcriptase inhibitors (RTIs) and protease inhibitors (PIs). METHODS: Samples obtained at baseline and after 8 weeks of therapy from 16 heavily pretreated patients were analysed for genotypic and phenotypic resistance. Genotypic resistance was analysed in cell-associated DNA and plasma HIV-RNA using direct sequencing. Phenotypic resistance was analysed in a PBMC-based assay and in a recombinant virus assay. Plasma viral load was measured at baseline and after 2, 4 and 8 weeks of therapy. RESULTS: The majority of patients was genotypically and phenotypically resistant to lamivudine, abacavir, zidovudine and PIs, whereas 50% of the patients showed resistance to nevirapine at baseline in at least one of the methods used. After 8 weeks of salvage therapy, no additional development of resistance against nucleoside reverse transcriptase inhibitors and PIs could be detected. However, the amount of patients resistant to nevirapine increased to 83%. When the patients were divided into two groups according to baseline resistance against nevirapine, a significantly higher transient reduction in viral load was observed in patients with nevirapine-sensitive HIV at baseline compared to patients with resistant HIV at baseline. CONCLUSION: The transient effect of salvage therapy including abacavir and nevirapine was due to the effect of nevirapine. The lack of effect of abacavir was most likely due to cross-resistance between abacavir and lamivudine/zidovudine used in previous treatment.
Anti-HIV Agents↗
[Use of antiretroviral chemoprophylaxis after occupational HIV exposure].
The study describes the use of postexposure antiretroviral prophylaxis (PEP) after occupational exposure to HIV in Denmark in the period 1/1 1997-31/12 1998. Forty-seven accidentally exposed persons received PEP in this period, of whom 14 were nurses, 13 physicians and 11 were not employed in the health care system. In 23 cases side effects to PEP were described. In 18 cases the index person was i.v. drug abuser and in 11 cases homosexual/bisexual men. In 18 cases the HIV status of the index person was unknown at the time of exposure. Ten of these index persons were subsequently tested and all found HIV-negative. It is concluded, that the frequency of occupational exposure to HIV is unacceptably high. Further it is emphasised that in cases where the HIV status of the index person is unknown, PEP should only be instituted if the index person is at risk of being HIV infected and has signs of HIV infection.
Adolescent↗
[Severe stomatitis caused by Mycoplasma pneumoniae infection].
Mycoplasma pneumoniae infection is sometimes followed by systemic reactions such as erythema multiforme major/Stevens-Johnsons syndrome. In the described case, a 30 year-old man developed severe inflammation of the oral mucous membranes following respiratory infection with Mycoplasma pneumoniae. There was also conjunctivitis and diarrhoea, and a target-like eruption was seen on the penis, but apart from slight perioral erythema and periorbital swelling, no further skin involvement was seen. The patient was treated with macrolide antibiotics for 14 days and gradually recovered.
Adult↗
Regional survival differences across Europe in HIV-positive people: the EuroSIDA study.
OBJECTIVES: To analyse the survival differences between macro-regions of Europe (northern, central and southern Europe) between 1994 and early 1999, and their possible association with antiretroviral treatment differences. DESIGN: From September 1994 the EuroSIDA study has prospectively followed non-selected HIV-infected people from 50 clinical sites in 18 European countries (n = 7331). METHODS: Cox proportional hazards models were used to compare death rates between regions and to investigate the relationship between treatment usage and regional mortality rates. Kaplan-Meier curves were used to compare survival from the first CD4 lymphocyte count of < 200 x 10(6)/l or < 50 x 10(6)/l. RESULTS: At the time of analysis, the median follow-up was 21 months and there was a total of 1544 deaths. In people with a CD4+ cell count that fell below 200 or 50 x 10(6)/l those from central Europe had a better prognosis compared with those from the two other regions (P < 0.05). Patients from central Europe were more frequently exposed to reverse transcriptase inhibitors and protease inhibitors compared with patients from other regions (P < 0.001). There was a significant difference in risk of death between regions after adjustment for baseline differences in demography, presence of AIDS and level of immunodeficiency (risk of death in central Europe was 37% lower than that in southern Europe (P < 0.0001) and 33% lower than in northern Europe (P < 0.0001)). After adjustment for use of individual antiretroviral agents, intensity of treatment regimen, CD4 lymphocyte count, weight, haemoglobin and development of AIDS as time-dependent covariates, the differences became much smaller (risk in central Europe 13% lower than that in southern Europe (P = 0.071) and 15% lower than in northern Europe (P = 0.054). CONCLUSION: Antiretroviral therapy has been used more aggressively in Europe in recent years, resulting in improved prognosis. In this study we observed that the HIV mortality rate in central Europe was significantly lower than those in northern and southern Europe in the period 1994 to early 1999. This finding appears to be due to the effect on survival of different treatment policies and drug availability in the three regions of Europe during this time period, with central European countries, on average, having introduced more aggressive treatment strategies earlier.
Adult↗
Can chemoprophylaxis against opportunistic infections be discontinued after an increase in CD4 cells induced by highly active antiretroviral therapy?
BACKGROUND: In the 'USPHS/IDSA Guidelines for Prevention of Opportunistic Infections in Persons Infected with Human Immunodeficiency Virus', the indications for chemoprophylaxis are based on nadir CD4 cell count. Many patients have, however, experienced an increase in CD4 cell count after the introduction of highly active antiretroviral therapy (HAART). OBJECTIVES: To assess incidences of opportunistic infections after discontinuation of chemoprophylaxis in HIV-infected patients, who have experienced a HAART-induced increase in CD4 cell count. METHODS: The Danish guidelines for chemoprophylaxis against opportunistic infections in HIV-infected patients were revised in late 1997, allowing discontinuation of chemoprophylaxis after initiation of HAART if the CD4 cell count remained above a specified limit for more than 6 months. Consecutive patients were followed, and incidences of opportunistic infections after discontinuation of chemoprophylaxis were assessed. RESULTS: A total of 219 patients discontinued Pneumocystis carinii pneumonia (PCP)-chemoprophylaxis (12% maintenance therapy). One case of PCP was diagnosed within 174 person-years (PY) of follow-up, resulting in an incidence of 0.6 cases/100 PY follow-up (95% confidence interval, 0.0-3.2). No cases of cerebral toxoplasmosis, cytomegalovirus chorioretinitis, or disseminated Mycobacterium avium infection were observed. Follow-up time for these was, however, limited. CONCLUSION: PCP-chemoprophylaxis can be safely discontinued after HAART-induced increase in CD4 cell count to more than 200 x 10(6) cells/l. Among consecutive patients who discontinue chemoprophylaxis according to well-defined guidelines, the observed incidence of PCP is below those reported earlier in patients with similar CD4 cell count.
AIDS-Related Opportunistic Infections↗
[Experiences with antiretroviral combination therapy].
The purpose of the study was to evaluate the efficacy of treating of HIV infected patients with two nucleoside analogues and one protease inhibitor in clinical practice. Sixty-one patients were included and followed with respect to plasma HIV-RNA, CD4 cell count and side effects up to one year. Median plasma HIV-RNA was reduced from 20,000 to < 200 copies/ml, and the percentage of patients with plasma HIV-RNA < 200 copies per ml increased from 7.5% to 65.2%. The CD4 cell count increased from 180 to 300 x 10(6)/l. Among 49 patients who remained on therapy, the percentage of patients with plasma HIV-RNA < 200 copies/ml increased from 9.8% to 73.7%. It is concluded that triple drug antiretroviral treatment shows significant effects on plasma HIV-RNA and CD4 cell count, and that the results obtained in clinical practice are comparable to results reported from controlled clinical trials.
Adult↗
Combination therapy containing ritonavir plus saquinavir has superior short-term antiretroviral efficacy: a randomized trial.
OBJECTIVES: To compare the efficacy and safety of indinavir 800 mg three times a day, ritonavir 600 mg twice a day, and a combination of ritonavir 400 mg twice a day and saquinavir 400 mg twice a day, when administered with two nucleoside analogues. DESIGN: A randomized, open-labelled, controlled trial. Two hundred and eighty-four patients started randomized treatment. The primary end-point was the proportion of patients with HIV RNA of 200 copies/ml or less (Roche Amplicor) and HIV RNA of 20 copies/ml or less (Roche ultradirect assay) at 6 months. Analysis was performed as intent-to-treat, and missing values were accounted for as failures. RESULTS: As of 1 May 1998, 269 patients should have completed 24 weeks of treatment. The proportion of patients with HIV RNA of 200 copies/ml or less was 71% (indinavir), 67% (ritonavir), and 82% (ritonavir + saquinavir), P = 0.07. In antiretroviral drug-naive patients (n = 119), the corresponding figures were 63, 57, and 89% (P < 0.01), whereas among drug-experienced patients (n = 165) 77, 74, and 77% had HIV RNA of 200 copies/ml or less (P = 0.90). The same pattern was observed in the ultradirect analysis. All three regimens were generally safe, but significantly more patients in the ritonavir group (37%) stopped treatment because of adverse drug reactions compared with the indinavir group (8%) and the ritonavir plus saquinavir group (16%) (P < 0.001). CONCLUSIONS: Treatment with saquinavir plus ritonavir in combination with two nucleoside analogues is generally safe, and has superior short-term antiviral efficacy compared with indinavir and ritonavir also combined with two nucleoside analogues in antiretroviral drug-naive patients. Further follow-up is needed to determine the durability of the viral response.
Adult↗
Saquinavir hard gel suppresses viral load insufficiently in HIV-infected patients naive to anti-retroviral therapy: a retrospective cohort study.
Protease inhibitors are important components in anti-retroviral regimens. In this retrospective study 29 HIV-infected patients treated with a regimen of zidovudine, lamivudine and saquinavir hard gel in 1 centre in Denmark were compared with 58 patients treated with zidovudine, lamivudine and ritonavir or indinavir followed at 5 other centres in Scandinavia. All patients were naive to anti-retroviral therapy prior to institution of the actual anti-retroviral regimen and were followed for a median of 1.3 and 1.4 y respectively. The 2 groups did not differ significantly with respect to age, gender, route of infection, ethnic background, viral load, CD4 count, AIDS at baseline or frequency of clinical controls. Six and 12 months after initiating anti-retroviral therapy, 31% and 34% of the patients on the saquinavir regimen obtained HIV-RNA < or = 500 compared with 76% and 73% in the control group (p < 0.001). In contrast to viral load, the increase in CD4 count did not differ significantly between the 2 groups. In conclusion, we found that with respect to suppression of viral load a regimen of saquinavir, zidovudine and lamivudine seemed to be inferior to a regimen of zidovudine, lamivudine and ritonavir or indinavir.
Adult↗
Low levels of inorganic lead noncompetitively inhibit mu-calpain.
Calpain is a ubiquitous calcium-dependent cysteine protease, whose cytoskeletal protein substrates suggest that it may be important in neuronal differentiation. Lead (Pb2+) is known to substitute for Ca2+ in a variety of intracellular processes, and interferes with the development of hippocampal neurons in vitro. We found that free Pb2+ at 1 nM does not activate calpain in the absence of Ca2+. Pb2+ inhibited the activity of calpain; the degree of calpain inhibition was dependent on an interaction between concentrations of both Ca2+ and Pb2+. In the presence of 1 microM free Ca2+, 10 pM free Pb2+ reduced calpain activity, but in the presence of 100 microM free Ca2+, 1 nM free Pb2+ failed to inhibit calpain. This provides evidence that Pb2+ competes for the Ca2+ binding sites on calpain. In the presence of 40 microM free Ca2+, 1 nM free Pb2+ significantly reduces Vmax without altering Km, suggesting that Pb2+ acts as a noncompetitive inhibitor of calpain. Inhibition of calpain is one mechanism by which Pb2+ may interfere with neuronal development.
Calcium↗
Blunted cardiovascular and catecholamine stress reactivity in women with bulimia nervosa.
Cardiovascular and catecholamine responses to mental stressors were investigated in women with bulimia nervosa (BN) and in healthy control subjects. Fifteen women with BN and 15 control subjects completed psychosocial questionnaires before laboratory testing, where they were exposed to an interpersonally based speech stressor and a serial math task. Blood pressure, heart rate, epinephrine, norepinephrine and, via impedance cardiography, systolic time intervals, cardiac output and total peripheral resistance were measured at rest and during stress. Results indicated that BN was associated with blunted sympathetic activation in response to mental stress, indicated by increased pre-ejection period responses and blunted systolic blood pressure, heart rate and epinephrine responses. In contrast, women with BN had elevated cortisol levels when compared with control women. In addition, despite equivalent performance between groups, bulimic women reported feeling significantly more confused, frustrated, inadequate and dissatisfied with their performance during tasks. Psychosocial questionnaires also indicated that women with BN perceived more stress, had worse coping skills, lower self-esteem and sense of mastery, reported less social support, had worse mood, had greater anxiety and were more depressed when compared with control women. These results are interpreted as reflecting physiological and psychological profiles indicative of distress vs. active effort coping in BN.
Adult↗