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Biomedical subjects

V Faber

Publications and source records attributed to V Faber.

At least 55 records · Page 3Linked to original sources

Inhibition of HIV replication in vitro by fusidic acid.

A 58-year-old man with AIDS improved clinically after the introduction of fusidic acid, 500 mg three times a day orally, to his therapeutic regimen. Fusidic acid may have had a direct effect against HIV. Fusidic acid has anti-HIV activity in vitro at levels readily attainable in vivo. The drug does not appear to be a reverse transcriptase inhibitor and its mode of action against HIV is unknown. Fusidic acid can be given orally and has few side-effects. These results justify fuller evaluation of fusidic acid as therapy against AIDS and HIV infection.

Acquired Immunodeficiency Syndrome↗

Staphylococcus aureus bacteremia in patients with hematological malignancies and/or agranulocytosis.

A total of 6,253 cases of Staphylococcus aureus bacteremia, including 274 (4.4%) endocarditis cases, were registered in Denmark in the period 1975-1984. Patients with hematological malignancies and/or agranulocytosis accounted for 479 of the bacteremia cases. The incidence of endocarditis in this group of patients was only 0.4% as compared to 4.7% in other patients with staphylococcal bacteremia (p less than 0.01). The lower incidence of endocarditis complicating bacteremia in these patients may justify a shorter course of therapy than usually recommended for suspected endocarditis. Patients with hematological malignancies and other patients with agranulocytosis had a higher mortality (49 and 46%, respectively) than other patients with S. aureus bacteremia (33%). The highest mortality was found in patients with multiple myeloma (71%, p less than 0.01), the lowest in patients with acute lymphocytic leukemia (28%, p less than 0.01). The higher mortality in these patients may indicate that empiric antibiotic regimens in granulocytopenic patients should include a specific anti-staphylococcal agent.

Aged↗

Histamine release from basophil leukocytes induced by microbial antigen preparations in patients with AIDS.

Type I allergy against some common microorganisms was investigated in 14 patients with AIDS and 11 human immunodeficiency virus (HIV) antibody-positive homosexual men, and in a control group consisting of 13 heterosexual men without HIV antibodies. Basophil histamine release technique was used as a sensitive method to detect type I allergy against Candida albicans (CA), Herpes simplex virus type I (HSV-I) and cytomegalovirus (CMV). Of the 14 AIDS patients 11 (78%) showed significant histamine release when stimulated with CA, and HSV-I caused release in 10 (71%), whereas no response was obtained by CMV. In the group of HIV antibody-positive men only one released histamine when stimulated with CA and HSV-I and this patient also had lymphadenopathia. In contrast to these results, no release of histamine was obtained in the control group consisting of 13 heterosexual men. The histamine release caused by CA and HSV-I is mediated by an immunological reaction, since the release was abolished and regained by removal from and refixation to the cell surface of the cell-bound immunoglobulins. These results suggest an involvement of type I allergy as a pathogenetic co-factor in some infections in AIDS, and allergic type I reactions to CA and HSV-I might be an indicator for the presence of manifest AIDS.

Acquired Immunodeficiency Syndrome↗

Strict protective isolation in allogenic bone marrow transplantation: effect on infectious complications, fever and graft versus host disease.

Complete microbial decontamination (laminar air flow room, sterile nursing and oral administration of cefamandole, gentamicin and nystatin) was carried out in 65 consecutive patients prior to allogeneic BMT for leukaemia (n = 58) or aplastic anaemia (n = 7). Very few microorganisms persisted during the post-transplant treatment period, and the gut became sterile in all except for Candida in 11 patients. Six uncomplicated septicaemias, all with persistent organisms simultaneously present in the mouth (Pseudomonas 3, Serratia 1, Candida 2) occurred during a total of 1,360 days with granulocyte counts less than 0.5 X 10(9)/l. Post-transplant fever occurred in 52 patients, exceeding 40 degrees C in 25. Guided by the surveillance cultures only 46% of 43 unexplained febrile reactions were treated with systemic antimicrobials. Significant acute graft versus host disease (AGVHD) occurred in 14 (27%) of 52 patients receiving standard prophylaxis and HLA-matched grafts; immunosuppressive treatment was needed in 8 cases (16%). Thus, the additional costs of total microbial decontamination appear partially regained by a decreased morbidity and a reduced need for antimicrobial and immunosuppressive treatment, although neither fever nor AGVHD could be prevented.

Adolescent↗

The effect of foscarnet (phosphonoformate) on human immunodeficiency virus isolation, T-cell subsets and lymphocyte function in AIDS patients.

Foscarnet was administered by continuous intravenous infusion in 15 patients with the acquired immunodeficiency syndrome (AIDS) in an open, uncontrolled study. Mean steady state serum concentrations of foscarnet was 261 mumol/l. Treatment was given for 6-21 days, median 14 days, being interrupted prematurely due to renal function impairment in seven patients, and due to other reasons in three patients. Foscarnet therapy was accompanied by improvement of some, probably cytomegalovirus (CMV) related, symptoms but did not otherwise affect the clinical condition of the patients. The occurrence of positive CMV cultures decreased significantly during therapy. Human immunodeficiency virus (HIV) detection by culture was positive in 70-80% of cultures and was unaffected by foscarnet treatment. Eight patients had detectable, free HIV antigen in serum before therapy, and in five of these HIV antigen disappeared during therapy, but reappeared 4-23 weeks after therapy. No patient lost HIV antigen, except during foscarnet therapy. No patient became HIV antigen positive during foscarnet therapy. Immunological parameters did not change during or after foscarnet therapy. Renal function impairment was seen in 9 patients (95% confidence limits, 32-84%), apparently due to reversible tubular damage. At follow-up, serum creatine was normal in all surviving patients. Concomitant medication may have contributed to the renal side-effects. Severe renal function impairment, i.e. serum creatinine above 0.25 mumol/l, was only seen in patients who at the start of foscarnet therapy were chronically affected by their disease. Thus, foscarnet reduces HIV antigen production in AIDS patients. Renal function impairment limits foscarnet use in AIDS patients, but in individuals with less severe manifestations of HIV infection, this side effect may be less frequent.

Acquired Immunodeficiency Syndrome↗

Blood monocyte and neutrophil functions in the acquired immune deficiency syndrome.

The acquired immune deficiency syndrome (AIDS) is characterized by infections with microorganisms against which phagocytes (especially monocytes/macrophages) play an important role. Therefore, various functions of blood monocytes and neutrophils were tested in 16 patients with AIDS. Neutrophil chemotactic responses towards casein and N-formyl-methionyl-L-leucyl-L-phenylalanine were depressed in patients with a short duration of disease (n = 9), whereas they were normal in those with a longer duration (n = 5), P less than 0.05. Neutrophil superoxide anion release was normal. In contrast, we found no evidence of an altered monocyte activity in the patients, since chemotactic responsiveness, phagocytosis of opsonized Candida albicans, and superoxide anion release were all normal. These findings suggest that the depressed neutrophil chemotaxis may play an important role in the high incidence of opportunistic infections in AIDS. Furthermore, it appears that in AIDS the immune deficiency does not extend to peripheral blood monocytes, but it does not exclude the possibility that the function of tissue macrophages is abnormal.

Acquired Immunodeficiency Syndrome↗

Correlation between donor cytomegalovirus immunity and chronic graft-versus-host disease after allogeneic bone marrow transplantation.

Chronic graft-versus-host disease (GvHD) in bone marrow allograft recipients is frequently preceded by a cytomegalovirus (CMV) infection. To elucidate whether an immune reaction of transplanted donor cells against CMV was involved in the pathogenesis of chronic GvHD, the effect of donor pretransplant CMV immune status on chronic GvHD incidence was analyzed. In 43 bone marrow recipients at risk, the 2-yr cumulative chronic GvHD probability was 55% when the donor was immune, in contrast to 16.5% when the donor was non-immune (p less than 0.002). No correlation between recipient pretransplant CMV immunity and chronic GvHD was observed. Donor CMV immunity did not correlate with acute GvHD or posttranplant CMV infection and seemed to predispose for chronic GvHD regardless of donor and recipient age. However, the proportion of CMV immune donors increased with increasing donor and recipient age. This may account for the higher incidence of chronic GvHD in older patients. The present study suggests that chronic GvHD may be mediated by a reaction of immune donor cells against CMV infected recipient cells.

Acute Disease↗

Opsonic activity of serum in the acute phase of meningitis.

The present study was designed to determine the opsonic activity of serum obtained from meningitis patients in the acute stage of their illness. This study was part of a Danish multicentre prospective study on various aspects of meningitis for a 12-month period. The opsonic activity of serum was determined by a phagocytosis and a chemiluminescence assay using human peripheral blood polymorphonuclear leukocytes. The mean chemiluminescence and phagocytosis indices determined in the sera of 58 patients suffering from various forms of bacterial or non-bacterial meningitis did not differ significantly from that of control sera. Although sera of 4 patients with pneumococcal, 3 with meningococcal, and 1 with streptococcal meningitis exhibited lower opsonic activity than the control sera in the chemiluminescence assay, their values in the phagocytosis assay were similar to control value. It is concluded that serum opsonic activity in meningitis patients is normal and similar to that of healthy individuals.

Acute Disease↗

Long-term seropositivity for human T-lymphotropic virus type III in homosexual men without the acquired immunodeficiency syndrome: development of immunologic and clinical abnormalities. A longitudinal study.

The long-term effects of seropositivity for human T-lymphotropic virus type III (HTLV-III) on T-lymphocyte subsets and health status were evaluated in longitudinal studies of 250 initially healthy homosexual men. The relative risk of having an inverted T-lymphocyte helper-to-suppressor ratio rose from 14.3-fold among short-term seropositive subjects (less than 19 months) to 46.9-fold among long-term seropositive subjects (greater than 29 months) in comparison with the risk among seronegative subjects. Overall, 91.7% of long-term seropositive men had inverted ratios, compared with 12.9% of seronegative men. None of the seropositive men who developed an inverted ratio later reestablished a normal ratio. Both decreased T-helper cell number and percentage (p = 0.003) and increased T-suppressor cell number and percentage (p = 0.03) were significantly correlated with duration of seropositivity. Among seropositive persons, lymphadenopathy was a highly significant short-term as well as long-term consequence, whereas diarrhea, oral thrush, and herpes zoster were correlated with long-term seropositivity. Overall, 50% of long-term seropositive men compared with 16% of seronegative men developed at least one of five clinical symptoms (p less than 0.003). We conclude that a high proportion of persons infected with HTLV-III will develop measurable immunologic and clinical abnormalities.

Antibodies, Viral↗

Ketoconazole and cyclosporine A: combined effects on rat renal function and on serum and tissue cyclosporine A concentration.

The effects of ketoconazole (Kcnz) on cyclosporine A (CyA) serum levels and CyA-nephrotoxicity were studied. To rats later anesthetized with pentobarbital sodium, CyA 12.5 and Kcnz 20 mg/kg/day (n = 20), or CyA 12.5 mg/kg and Kcnz-vehicle (n = 21), was dosed. To rats anesthetized with etomidate (n = 14), CyA 12.5 mg/kg and Kcnz-carrier was dosed. S-CyA was monitored during 14 days, and then the rats were investigated with clearance (C) methods (inulin [(in), lithium (Li)], sodium, and potassium), and liver (L) and kidney (K) CyA was measured. Kcnz increased S-CyA, L-CyA and K-CyA (+50 -80%). There were significant (p less than 0.05) correlations between S- and L- or K-CyA. Kcnz increased CyA nephrotoxicity: Mean Cin was 1.012 ml/min/gKW (kidney weight) after CyA treatment (a subnormal value), but decreased to 0.556 ml/min/gKW in the group also given Kcnz (p less than 0.001). CLi decreased from 0.135 to 0.048 ml/min/gKW (p less than 0.001), and absolute proximal tubular reabsorption decreased from 0.877 to 0.508 ml/min/gKW (p less than 0.001), while the fractional reabsorption in the proximal tubule (FPR), expressed as a percentage of GFR, increased from 86.9 to 91.6% (p less than 0.005). Thus, after Kcnz treatment to rats given CyA 12.5 mg/kg/day, their renal function was indistinguishable from that in rats given CyA 25 mg/kg/day.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia↗

Variation in human T lymphotropic virus III (HTLV-III) antibodies in homosexual men: decline before onset of illness related to acquired immune deficiency syndrome (AIDS).

Western blot analysis was used to document the development and changes in human T lymphotropic virus III (HTLV-III) antibody among Danish homosexual men followed longitudinally over three years. Reactivity against p15, p24, and p55 appeared earliest. After seroconversion the antibody concentration fluctuated, but in one instance a steady decline in banding intensity was seen during the 18 months before onset of the acquired immune deficiency syndrome (AIDS) and throughout the remaining eight months of his life.

Acquired Immunodeficiency Syndrome↗

Coincidental fluctuations of humoral immunity and clinical progression in a patient with subacute sclerosing panencephalitis.

Serum and cerebrospinal fluid were obtained from a 6-year-old male with subacute sclerosing panencephalitis (SSPE). Specimens were collected over a 9-month period beginning in the unusually acute phase and ending in a more quiescent phase of the disease. Immune complexes, auto-antibodies and viral antibodies were measured by radio-immunoassays. Fluctuations in these humoral immune parameters coincided with cessation of the acute phase of this disease. The results show that neurological changes in SSPE patients can be reflected in immune responses within both the peripheral circulation and the central nervous system.

Antibodies, Viral↗

Frequency, phage types and antibiotic resistance of Staphylococcus aureus isolated from blood cultures in Denmark 1975-1981.

In the period 1975-1981, 4060 cases of Staphylococcus aureus bacteremia were recorded in Denmark, and the corresponding strains were examined. The percentage of strains, resistant to penicillin only, rose to 82, and the percentage of multiply-resistant strains fell to five. Newer phage types (94, 96 and 95) increased from 10% to 27% of the material. These strains were usually resistant only to penicillin, but produced large amounts of penicillinase. The ample penicillinase production has also been characteristic for previous epidemic strains, and it is furthermore correlated to mortality. The overall mortality of 34.6% was lower than that of the preceding period. Mortality rates were highest in elderly patients, nosocomial cases, patients with serious primary diseases and endocarditis cases.

Adult↗