A death from combined alcohol and benzodiazepine poisoning in a non-medical detoxification unit.
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Alcoholic Intoxication↗
Biomedical subjects
C Pedersen
Publications and source records attributed to C Pedersen.
The effect of treatment with zidovudine with or without acyclovir on HIV p24 antigenaemia in patients with AIDS or AIDS-related complex.
OBJECTIVE: To evaluate changes in serum HIV p24-antigen levels in a subset of patients who participated in a European/Australian double-blind, placebo-controlled trial evaluating the efficacy of zidovudine (250 mg every 6 h) alone or in combination with acyclovir (800 mg every 6 h) in patients with AIDS, AIDS-related complex (ARC) or Kaposi's sarcoma (KS). DESIGN: Double-blind, placebo-controlled randomized clinical trial of less than or equal to 6 months' therapy. SETTING: Samples were obtained from patients attending teaching hospital outpatient clinics in seven European countries and Australia. SUBJECTS: One hundred and ninety-seven HIV-infected patients (60 with AIDS and 137 with ARC or KS). MAIN OUTCOME MEASURES: Serum HIV p24-antigen levels measured using the Abbott HIV solid-phase enzyme immunoassay. RESULTS: Of 76 ARC/KS patients who were initially HIV p24-antigen-positive, one out of 25 randomized to placebo, eight out of 23 to zidovudine and 11 out of 28 to the zidovudine/acyclovir combination became antigen-negative. The proportion of patients who became antigen-negative was significantly higher in both the zidovudine group (P = 0.016) and the zidovudine/acyclovir group (P = 0.004), compared with the placebo group. There were no statistical differences between the zidovudine and the zidovudine/acyclovir groups. During the trial p24-antigen levels in the zidovudine-treated patients reached their minimum after 4-8 weeks of therapy, and tended to increase gradually thereafter. Disease progression occurred irrespective of whether p24-antigen levels declined during therapy. No association between p24-antigen responses to therapy and baseline disease stage, Karnofsky score or baseline CD4 cell count was detectable. CONCLUSION: Acyclovir does not potentiate the effect of zidovudine on p24-antigen levels. Change in antigen level in response to antiviral therapy needs further investigation before it is used as a surrogate marker for clinical efficacy of antiviral therapy.
AIDS-Related Complex↗
One-year follow-up on the safety and efficacy of isoprinosine for human immunodeficiency virus infection. Scandinavian Isoprinosine Study Group.
The safety and clinical impact of isoprinosine in HIV-infected individuals were assessed in a multicentre, randomized, double-blind, 24-week study phase, followed by an optional 24-week open treatment phase. The results of the double-blind phase have been reported. Of 866 HIV-seropositive patients randomized, 832 subjects were eligible for efficacy analysis. On completion of the double-blind phase, 596 patients started open treatment. All patients were evaluated with regard to progression to AIDS and/or death. Within 48 weeks, 10/412 (2.4%) patients assigned isoprinosine and 27/420 (6.4%) patients assigned placebo progressed to AIDS (P = 0.005). Intention-to-treat analysis showed identical results. Viewing the open treatment phase in isolation revealed no difference in progression rates between those treated and those not receiving the drug, perhaps reflecting the higher proportion of patients receiving zidovudine or PCP prophylaxis in the latter group. No severe adverse reactions or toxicities were observed. We conclude that HIV-seropositive patients without AIDS may be safely and effectively treated with isoprinosine.
Acquired Immunodeficiency Syndrome↗
Effect of fusidic acid on interleukin-1 (IL-1)- and IL-6-induced pancreatic beta-cell functions in rats.
Fusidic acid and its sodium salt (fusidin) are anti-staphylococcal drugs with a steroidal primary structure. Both compounds have been shown to prevent the lymphocyte co-stimulatory activities of the cytokines, interleukin (IL)-1 and IL-6, in a manner similar to that of cyclosporin A. As shown in this paper, fusidin also prevents the inhibitory effect of human recombinant IL-1 beta (rIL-1 beta) and the stimulatory effect of human rIL-6, on glucose-induced insulin production in vitro by normal rat pancreatic islets. The drug also inhibited rIL-1 beta-induced IL-6 production by the islets. Fusidin showed a dose-related effect at pharmacologically relevant concentrations from 3 to 30 micrograms/ml, and the drug was progressively less active when added 1, 4 and 24 h after rIL-1 beta. Electron microscopical studies showed that beta cells cultured for 72 h with rIL-1 beta accumulated less lipid in the presence of fusidin, most probably reflecting the functionally protective effect of the drug. Other characteristic ultrastructural changes induced in beta cells by rIL-1 beta were, however, not altered. It is suggested that fusidin may prove clinically effective as a modulator of IL-1- and IL-6-induced changes in beta-cell functions.
Animals↗
Time-related decrease in diffusion capacity in HIV-infected patients with impaired immune function.
The purpose of this study was to investigate acute and time-related changes in lung function, i.e. forced expiratory volume in 1 second (FEV1), vital capacity (VC) and transfer factor (KCO) in HIV-infected patients with CD4 cell counts less than 400 x 10(6)/l. 66 males with no history of HIV-related pulmonary symptoms participated in a prospective lung function study for 9 months with 3-month intervals between examinations. 15/66 patients (23%) developed acute pulmonary symptoms, i.e. dyspnea (n = 12), cough (n = 13), fever greater than 38 degrees C (n = 13) and interstitial infiltrates on the X-ray (n = 9). Among the 51 asymptomatic patients, a significant time-related decrease in KCO (median decrease of 7%) was found, whereas no significant change in FEV1 or VC was observed during the study. Baseline KCO, i.e. KCO at entry, was found to be significantly higher in the asymptomatic patients (102% predicted (pred.) than in those patients who developed pneumonia (88% pred.). Development of pulmonary symptoms was both followed by a significant decrease in KCO (median decrease 17%), FEV1 and VC. We therefore conclude that HIV-infected patients with impaired immune function have in the absence of pulmonary symptoms a decrease in KCO. In case of pneumonia an acute decrease in both KCO, FEV1 and VC occurs.
Adult↗
Anti-diabetogenic effect of fusidic acid in diabetes prone BB rats.
Fusidic acid and its sodium salt (fusidin) are anti-staphylococcal drugs. In vitro studies have shown that they prevent the lymphocyte co-stimulatory activities of the cytokines IL-1 and IL-6 in a manner similar to that of cyclosporin A, and prevent the inhibitory effect of IL-1 on glucose-induced insulin production. As IL-1 and IL-6 are thought to play a role in the pathogenesis of Type 1 diabetes, the aim of this study was to investigate whether fusidin could influence the disease incidence of the spontaneously diabetic BB rat model. Accordingly, a group of 50 BB rats receiving fusidin dissolved in their drinking water were compared to a control group of 55 rats over a period of 200 days. The incidence of diabetes was found to be 52% in the experimental group and 71% in the control group (P < 0.05). The degree of insulitis and the number of islets at histological examination were similar among the non-diabetic animals whereas the diabetic fusidin-treated animals showed a higher degree of islet preservation than the diabetic control rats. The results are highly indicative of an anti-diabetogenic effect of fusidin.
Administration, Oral↗
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↗
Hydrogen fluoride-mediated synthesis of 1-thiotrehaloses involving reaction of D-glucose with hydrogen sulfide.
Hydrogen sulfide reacted with D-glucose in hydrogen fluoride solution to yield preponderantly alpha,alpha-1-thiotrehalose, beta,beta-1-thiotrehalose, and the alpha,beta anomer. Conditions were found under which the thiotrehaloses were obtained in the respective proportions of 8:5:5.
Carbohydrate Conformation↗
Steric and electronic effects in the formation of dihexulose dianhydrides. Reaction of racemic sorbose in anhydrous hydrogen fluoride and a facile synthesis of D-sorbose.
Treatment of DL-sorbose with anhydrous hydrogen fluoride gave a high yield of alpha-D-sorbopyranose alpha-L-sorbopyranose 1,2':2,1'-dianhydride. Similarly a mixture of D-fructose and D-sorbose gave a good yield of beta-D-fructopyranose alpha-D-sorbopyranose 1,2':2,1'-dianhydride. The formation of these products compared to the more complicated mixtures of compounds obtained by treatment of L-sorbose or D-fructose with hydrogen fluoride, is discussed in terms of conformations, and steric and electronic factors.
Carbohydrate Conformation↗
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↗
Isolation of HIV from cultures of purified CD4+ lymphocytes.
Isolation of HIV from cultures of CD4+ lymphocytes purified from peripheral blood by indirect panning was optimized and evaluated. Infectious HIV was isolated by single isolation attempts in 98% of 102 HIV-antibody-positive patients (55 had AIDS or ARC and 47 were clinically healthy). The average culture time required for positive cultures was largely independent of the CD4 count of the patients and 87% of the positive isolation cultures from both groups of patients became positive within 14 days of culture. An evaluation of the possible influence of media additives on propagation of HIV showed that: amphotericin-B had a suppressive effect on HIV replication at concentrations recommended for anti-fungal activity; recombinant and human interleukin-2 were equally suitable for both isolation cultures and for propagation of HIV, and polybrene, at a concentration of 2 micrograms/ml in the culture medium had a beneficial effect.
Amphotericin B↗
HIV-associated lymphoma: histopathology and association with Epstein-Barr virus genome related to clinical, immunological and prognostic features.
All 51 cases of HIV-related malignant lymphoma in Denmark diagnosed from 1983 to 1989 were reviewed. There were 12 Burkitt-type lymphomas, 30 immunoblast-rich lymphomas and 9 other lymphomas. Patients with immunoblast-rich lymphomas had significantly lower CD4 cell counts (median 60 vs. 188 x 10(6)/l, P less than 0.05), and more often a history of previous AIDS-defining illnesses (50% vs. 0%, P less than 0.005), compared with patients with Burkitt-type lymphomas. Epstein-Barr virus (EBV) DNA was demonstrated in 14 of 19 immunoblast-rich tumours, and in 2 of 7 Burkitt-type lymphomas (P = 0.10). Compared with EBV DNA-negative tumours EBV DNA-positive tumours were associated with lower CD4 cell counts (median 39 vs. 188 x 10(6)/l, P = 0.01). It is concluded that two main types of HIV-related malignant lymphoma exist. One is associated with severe immunosuppression, is often of immunoblast-rich morphology, and may be linked to EBV, whereas the other may occur in the absence of immunosuppression, is often of Burkitt-type morphology, and is probably not linked to EBV. In addition to these two main types, other non-Hodgkin lymphomas and Hodgkin's disease do occur.
Adult↗
The efficacy and safety of zidovudine with or without acyclovir in the treatment of patients with AIDS-related complex. The European-Australian Collaborative Group.
Our objective was to evaluate the efficacy and safety of zidovudine (250 mg every 6 h) alone or in combination with acyclovir (800 mg every 6 h) as treatment for AIDS-related complex (ARC). A double-blind, controlled clinical trial of 6 months therapy was conducted at teaching hospital ambulatory clinics in eight European countries and Australia; 199 patients were studied. Time to development of AIDS-defining opportunistic infections (OI) and AIDS-associated neoplasms, survival, performance status, body weight and CD4+ cell counts were measured. During the study six (9%) zidovudine recipients, five (7%) combination recipients and 12 (18%) placebo recipients developed AIDS-defining OI; the probability of developing an OI was 0.23, 0.09 and 0.08 for the placebo, zidovudine and combination recipients, respectively. Four patients in the placebo group, three in the zidovudine group and one in the combination group died during the study. Patients receiving zidovudine with or without acyclovir had moderate increases in CD4+ cell counts compared with placebo recipients and serum HIV p24 antigen level decreased significantly in all those receiving zidovudine. Fourteen (21%) patients in the zidovudine group and 16 (24%) in the combination group experienced bone-marrow suppression compared with three (5%) placebo recipients. Red-cell transfusions were administered to 6, 19 and 13% of placebo, zidovudine and combination recipients, respectively. These data confirm the efficacy of zidovudine therapy after 4 weeks' treatment in the reduction of development of OI in patients with ARC and support the use of a maintenance dose of 250 mg zidovudine 6-hourly. Given the increased development of OI in the treated groups compared with placebo during the first 4 weeks of therapy, we cannot exclude an initial adverse effect of zidovudine and recommend caution in the use of a loading dose of zidovudine. At 6 months there was no apparent difference in efficacy between the combination of zidovudine and acyclovir compared with zidovudine alone. Moreover, the addition of high-dose acyclovir resulted in a minimal increase in the risk of toxicity.
AIDS-Related Complex↗
Chronic pulmonary thromboembolism in dogs treated with tranexamic acid.
BACKGROUND: Many questions remain regarding the pathogenesis, natural history, diagnosis, and treatment of chronic thromboembolic pulmonary hypertension in patients. To answer such questions, we developed an animal model of this disorder. The brisk thrombolytic response of canines to acute embolism has, previously, prevented the establishment of such a model. METHODS AND RESULTS: The fibrinolytic inhibitor tranexamic acid was given orally to canines before, and for intervals after, pulmonary emboli were released from venous thrombi formed in vivo in femoral veins or the inferior vena cava. Preliminary studies disclosed that embolic residuals from femoral vein thrombi were not sufficient to cause significant, persistent pulmonary hypertension. With repetitive, larger thrombi embolized from the inferior vena cava, however, persistent pulmonary hypertension was achieved in most animals. CONCLUSIONS: Resolution of emboli in the canine can be inhibited by tranexamic acid. As in humans, a spectrum of embolic residuals is encountered, and the perfusion lung scan consistently underestimates the extent of embolic residuals. Studies of this animal model continue.
Animals↗
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↗
Prevalence of HIV infection in seronegative high-risk individuals examined by virus isolation and PCR.
HIV seronegative individuals with high-risk behavior were tested for HIV infection by sensitive virus isolation techniques using T4 lymphocytes and monocyte/macrophages, and by detection of proviral DNA using PCR with three different sets of nested primers. No evidence of HIV infection was found among the 31 seronegative high-risk subjects, either by virus isolation of by PCR (97.5% confidence limits, 0-11). Our results indicate that ongoing HIV infection in seronegative persons at high risk of infection is a rare event.
Acquired Immunodeficiency Syndrome↗
AIDS-related lymphoma. Histopathology, immunophenotype, and association with Epstein-Barr virus as demonstrated by in situ nucleic acid hybridization.
To investigate the range of pathology shown by acquired immune deficiency syndrome (AIDS)-related lymphomas arising in an epidemiologically well-defined group of patients, all cases of lymphoma recognized in Danish human immunodeficiency virus (HIV)-infected individuals up to the end of 1988 were studied. Twenty-seven cases (26 high-grade non-Hodgkin's lymphoma [NHL], 1 Hodgkin's disease) were found, to give a cumulative incidence rate of 8% among Danish AIDS patients. Morphologically most NHL patients were classified into two groups: 1) high-grade tumors with a predominant population of immunoblasts, either monomorphic or more often polymorphic with plasmacytic differentiation; 2) Burkitt-type. Of 26 NHLs, 22 had a B-cell paraffin-section immunophenotype and 4 were non-B, non-T. Epstein-Barr virus (EBV) DNA was demonstrated in tumor cells of 12 of 24 cases (50%) using in situ nucleic acid hybridization with a 35S-labeled probe in paraffin sections. Epstein-Barr virus DNA was found in 65% of group 1 and 20% of group 2 tumors. This study suggests the existence of two main groups of AIDS-related lymphoma with different pathogeneses. First there are immunoblast-rich lesions, which usually are associated with EBV and morphologically resemble lymphomas described in immunosuppressed organ-transplantation patients. Second there are Burkitt-type tumors in which EBV sequences are less common and that may be pathogenetically analogous to sporadic Burkitt's lymphoma.
Acquired Immunodeficiency Syndrome↗
Central nervous system involvement in human immunodeficiency virus disease. A prospective study including neurological examination, computerized tomography, and magnetic resonance imaging.
Sixty-seven patients with different stages of human immunodeficiency virus (HIV) infection (47 CDC group IV, 20 CDC groups II or III) were followed prospectively for a median of 18 months with neurological examination, magnetic resonance imaging (MRI), and computerized tomography (CT) to evaluate the incidence of the AIDS dementia complex (CDC definition) and other neurological complications. Ten patients developed CNS opportunistic infection or malignancy. Among the remaining 57 patients, 12 of 37 (32%) belonging to CDC group IV, and 1 of 20 (5%) belonging to CDC groups II/III developed the AIDS dementia complex (p = 0.03). MRI white matter lesions occurred in 32% of CDC group IV patients and 5% of CDC groups II/III patients (p = 0.03). The corresponding figures for brain atrophy at CT were 71% and 30% (p less than 0.01) and for neurologic signs 49% and 20% (p = 0.06). The development of the AIDS dementia complex was significantly associated with the occurrence of MRI white matter lesions and a CD4 cell count of less than 200 x 10(6)/l, whereas it was not statistical significantly associated with brain atrophy at baseline. It is concluded that the AIDS dementia complex is a common feature of late stage HIV infection. Brain atrophy occurs in a large percentage of HIV infected patients, but the clinical significance of this atrophy is not clear.
AIDS-Related Complex↗