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Biomedical subjects

F T Black

Publications and source records attributed to F T Black.

At least 19 recordsLinked to original sources
PubMed2003

The use of calcium carbonate in nelfinavir-associated diarrhoea in HIV-1-infected patients.

OBJECTIVES: To evaluate the efficacy of oral calcium supplements in HIV-infected patients with nelfinavir (NFV)-associated diarrhoea, and to investigate the influence on the pharmacokinetics of nelfinavir and the active metabolite M8. METHODS: An open-label prospective trial with enrolment of 15 patients with NFV-associated diarrhoea. Study subjects received either calcium carbonate or calcium gluconate/calcium carbonate in addition to highly active antiretroviral therapy (HAART), and were randomized to (i) calcium supplements for 14 days followed by 14 without calcium supplements, or (ii) 14 days without calcium supplements followed by calcium supplements for 14 days. Clinical endpoint was the severity of diarrhoea, graded and summarized for the specific 14 day-period. In the pharmacokinetic evaluation concentrations of NFV and M8 were measured before morning dosing, and 3 h after dosing. RESULTS: Nine patients were treated with calcium carbonate, and six with calcium gluconate/calcium carbonate. In the paired analysis, neither of the groups had a significant improvement in diarrhoea score when treated with calcium supplements (P = 0.34 and 0.46, respectively). We found no significant differences in the concentrations of NFV and M8 between the calcium and control periods. CONCLUSIONS: Oral calcium supplements did not significantly improve nelfinavir-associated diarrhoea. In the pharmacokinetic analysis calcium supplements did not induce major alterations in plasma concentrations of NFV and M8.

Adult↗
PubMed2002

Decreased urokinase receptor expression on granulocytes in HIV-infected patients.

Pericellular proteolysis initiated by receptor-bound urokinase-type plasminogen activator (uPA) is considered important for directed migration of granulocytes to inflammatory sites. Using flow cytometry and whole-cell binding of radiolabelled-uPA, we found a high level of uPA-receptor (uPAR) expression in granulocytes (3.9 x 104 +/- 0.9 x 104 sites/cell). Modulation of uPAR expression was assessed in the presence of chemoattractant gradients. Our findings demonstrate that interleukin (IL)-8, leukotriene B4(LTB4) and formyl-methionyl-leucyl-phenylalanine (f MLP) caused a dose-dependent upregulation of uPAR on granulocytes in healthy controls. Modulation of uPAR expression is known to regulate chemotactic response. As determined by flow cytometry, uPAR expression by granulocytes from human immunodeficiency virus (HIV)-infected patients was distinctly lower than that of healthy control cells (P < 0.001). However, upregulation of uPAR in response to chemoattractants was similar to that observed in healthy controls. In HIV-infected patients, the uPAR expression on granulocytes correlated (P < 0.001, n = 10) with the number of CD4+ blood cells. In contrast, the expression of IL-8 receptor, CD11b, CD18 and CD62 was not significantly altered in HIV-patients compared with healthy controls.

CD4 Lymphocyte Count↗
PubMed2001

The effect of nevirapine in combination with nelfinavir in heavily pretreated HIV-1-infected patients: a prospective, open-label, controlled, randomized study.

The purpose of the current study was to determine the efficacy and safety of nevirapine combined with nelfinavir and two nucleoside reverse transcriptase inhibitors (NRTIs) in patients previously exposed to highly active antiretroviral therapy (HAART). In a prospective, open-label, randomized study, 56 HIV-infected adults who had received HAART, including saquinavir hard gel capsule, ritonavir, or indinavir, were randomly assigned to receive nevirapine in addition to nelfinavir and two NRTIs. The proportion of patients who achieved an undetectable viral load (plasma HIV-RNA <200 copies/ml) at weeks 24 and 36 was significantly higher in the nevirapine group than in the control group (55% and 52% vs. 22% and 22%; p =.015 and p =.047). No differences in CD4 cell count or clinical outcome were observed. In the nevirapine group, 17% of patients discontinued treatment because of rashes. We conclude that the addition of nevirapine, when switching from one protease inhibitor-containing regimen to one containing nelfinavir, has a substantial effect on viral suppression.

Adult↗
PubMed2000

The immunofluorescence antibody test (IFAT) for the diagnosis of schistosomiasis used in a non-endemic area.

OBJECTIVE: To evaluate an immunofluorescence antibody test (IFAT) for diagnosis of schistosomiasis in nonimmune travellers and immigrants from endemic areas. METHODS: 65 patients (48 Danes and 17 immigrants) with schistosomiasis were included. The diagnosis of schistosomiasis was based on the presence of schistosome eggs in faeces, urine, sperm, rectal or bladder biopsies and/or the presence of specific antibodies determined by the serological immunofluorescence antibody test (IFAT). Egg excretion was detected using conventional methods and the IFAT performed on whole S. mansoni schistosomula worms, harvested after 8 weeks from mice. Two patterns of immunofluorescence were observed: Fluorescence in the gut of the schistosome called 'Gut Associated Antigen, GAA', and fluorescence of the surface of the schistosomula called 'Membrane Bound Antigen, MBA'. RESULTS: Eggs were found in 44% of the Danish patients and in 76% of immigrants. The diagnosis was based on a positive IFAT in 48% of the patients. In patients from nonendemic areas, the finding of antibodies against GAA was diagnostic while optimal sensitivity in the immigrants was reached by measuring antibodies against both GAA and MBA. CONCLUSION: In patients from nonendemic areas GAA is a sensitive marker of acute infection with schistosomiasis. In patients from endemic areas the demonstration of both GAA and MBA is necessary to properly identify long-lasting, nonacute infections. Egg-detection and/or measurement of CAA and CCA remain the methods of choice to monitor treatment as the immunofluorescence assay may remain positive for several years after treatment.

Adolescent↗
PubMed2000

The prevalence and significance of incidental paranasal sinus abnormalities on MRI.

Morphological changes in the paranasal sinuses are regularly noted on MRI, but little is known about the incidence and significance of these changes in the general population. The purpose of this study was 1) to classify the morphological changes in the paranasal sinuses seen on MRI 2) to investigate the prevalence, site and type of paranasal abnormalities and 3) to evaluate the significance of the findings by relating them to the presence of sinusitis symptoms, allergy, smoking habits and seasonal variations. In a one-year period, 404 patients referred to MRI for suspected intracranial neurological pathology were prospectively investigated. Before undergoing the scan the patients completed a questionnaire. The observed morphological conditions were classified so that mucous thickening < 5 mm was recorded as normal; > or = 5 mm, total sinus opacification or fluid and polyps as pathological. According to this classification 31.7% of the patients had pathological findings in the sinuses. A significantly higher incidence was found in the winter period and in patients with symptoms associated to sinusitis. "Blocked nose" was the only symptom occurring significantly more often in patients with pathological changes. There was no significant relationship between paranasal sinus abnormalities and sex, age, allergy, smoking habits, previous events of sinusitis or frequent events of colds. Criteria for pathological MRI findings in the paranasal sinuses are desirable and might improve the basis for a decision on the correct medical or surgical treatment.

Adult↗
PubMed1999

[Treatment of HIV infections and AIDS with protease inhibitor and two nucleoside analogs].

Until December 31st 1997, 163 HIV/AIDS patients were treated with HAART at the Department of Infectious Diseases, Aarhus University Hospital. The patients mainly received a combination of zidovudine, lamivudine and saquinavir. They were observed for an average period of 375 days. HAART was found to increase the amount of CD4 lymphocytes in peripheral blood and decrease the number of HIV-RNA copies. Both effects were seen to be more pronounced in patients naive to antiretroviral treatment. However, 64 patients had their protease inhibitor changed during the observation period, 53% due to failure of suppression of the viral load, 25% due to adverse events and 22% due to other reasons.

Acquired Immunodeficiency Syndrome↗
PubMed1999

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↗
PubMed1999

Extracellular and intracellular killing in neutrophil granulocytes of Staphylococcus aureus with rifampicin in combination with dicloxacillin or fusidic acid.

The effect of rifampicin in combination with dicloxacillin or fusidic acid on the extracellular and intracellular killing of Staphylococcus aureus in human neutrophil granulocytes in the presence of serum was studied. At the extracellular level rifampicin significantly reduced the bactericidal activity of dicloxacillin, but had an indifferent effect on the activity of fusidic acid. The combination of rifampicin with dicloxacillin or fusidic acid led to intracellular killing no different from that produced by rifampicin alone. However, owing to the high intracellular activity of rifampicin, the intracellular killing by the drug combinations was greater than that by dicloxacillin or fusidic acid alone.

Adult↗
PubMed1998

Alpha interferon therapy in Danish haemophiliac patients with chronic hepatitis C: results of a randomized controlled open label study comparing two different maintenance regimens following standard interferon-alpha-2b treatment.

Following a survey among all Danish haemophiliac patients 49 HIV-negative patients with chronic hepatitis C were offered enrollment in a randomized controlled open label study comparing two different maintenance regimens following standard interferon-alpha-2b treatment. Dose modifications and treatment discontinuation were based upon changes in transaminase levels. Forty-seven patients enrolled received 3 MU of alpha interferon thrice weekly (TIW) for 3 months. Twenty-six nonresponders had their dose increased to 6 MU TIW for an additional 3 months, while 21 responding patients continued on 3 MU TIW. At 6 months, 25 patients with a complete or a partial biochemical response were randomly allocated to either a fixed dose regimen (13 patients) (3 or 6 MU thrice weekly) or an individualized dose regimen (12 patients) tapering interferon dose from 3 or 6 MU by one-third every 2 months if transaminases were persistently normal. The remaining 22 biochemical nonresponders were followed for an additional 6 months without further treatment. After 12 months of treatment, 18 patients (38%) had a virological response, irrespective of regimen, and seven patients (16%) had a sustained virological and biochemical response after 6 months of follow up. Overall, the individualized treatment regimen did not seem to offer any advantage over the fixed dose regimen. The response to alpha interferon treatment in Danish haemophiliac patients with chronic hepatitis C immediately after treatment is comparable to that obtained in previous studies among nonhaemophiliacs. However, a sustained virological and biochemical response was seen in only 16% of treatment patients.

Adolescent↗
PubMed1998

The effect of dicloxacillin and fusidic acid on the extracellular and intracellular killing of Staphylococcus aureus.

The effect of dicloxacillin and fusidic acid used alone and in combination on the extracellular and intracellular killing of four isolates of Staphylococcus aureus in the presence of serum was studied. At the extracellular level, dicloxacillin (8 mg/L) had a bactericidal effect on all four isolates, whereas fusidic acid (64 mg/L) had a bacteriostatic effect on two isolates and no effect on the two other isolates. Fusidic acid significantly inhibited the extracellular bactericidal effect of dicloxacillin on two isolates. Intracellular killing was measured in human neutrophil granulocytes. Dicloxacillin (8 mg/L) significantly increased the intracellular killing of all four isolates, while fusidic acid (64 mg/L) significantly increased the intracellular killing of three isolates, but the killing was significantly lower than that of dicloxacillin. When the antibiotics were combined the intracellular killing of three of the isolates was significantly lower than that of dicloxacillin alone. The viability of the granulocytes and their ability to produce superoxide anion were not affected by the antibiotics. In conclusion, we found that the increased intracellular killing of S. aureus by dicloxacillin was inhibited by fusidic acid.

Adult↗
PubMed1997

[Yellow fever vaccination as prophylaxis of herpes labialis].

At some vaccination centres, it seems to be a clinical observation, that there is a reduction in the number of attacks of herpes labialis following yellow fever vaccination. We therefore conducted a double blind, prospective, randomized study to evaluate the efficacy of yellow fever vaccination against recurrent herpes labialis. Twenty-four patients with culture proven herpes labialis were allocated to either yellow fever vaccination or placebo (saline), with 12 persons in each group. After vaccination/ placebo the patients were followed for one year. The patients returned a letter every other month with information concerning the number of attacks during the period. Comparison of the data from the two groups after one year revealed no significant difference in the number of attacks between the two groups. In conclusion evaluation of the data from this study does not confirm the clinical observation that yellow fever vaccination may act as prophylaxis against herpes labialis.

Adult↗
PubMed1997

Chemotaxis and IL-8 receptor expression in B cells from normal and HIV-infected subjects.

To date, the activities of the alpha chemokines for human peripheral B cells from normal subjects (N-B cells) or from HIV-infected subjects (HIV-B cells) are not well established. No report on the IL-8R expression on N-B cells and HIV-B cells has been seen. We report in this work that the alpha chemokines IL-8 and growth-regulatory oncogene-alpha (GRO-alpha) induce a chemotactic migration of N-B cells and HIV-B cells via stimulating the IL-8RB on these cells. The chemotaxis of N-B cells can be inhibited by IFN-gamma and IL-2, and augmented by IL-4 and IL-13, whereas TNF-alpha and IL-10 have no influence. The chemotaxis of HIV-B cells can be inhibited by IFN-gamma and IL-2, and augmented by TNF-alpha, IL-4, and IL-10, whereas IL-13 has no influence. IL-8R are expressed more abundantly on freshly isolated HIV-B cells than N-B cells (51% and 15%, respectively). The IL-8R on N-B cells can be down-regulated by IFN-gamma, IL-2, and TNF-alpha (selectively on IL-8RA), and up-regulated by IL-4 and IL-13, whereas IL-10 has no influence. The IL-8R on HIV-B cells can be down-regulated by IFN-gamma and IL-2, and up-regulated by TNF-alpha, IL-4, and IL-10, whereas IL-13 has no influence. Importantly, N-B cell and HIV-B cell chemotaxis toward IL-8 and GRO-alpha can be blocked by anti-IL-8RB polyclonal Ab, but not by anti-IL-8RA polyclonal Ab. Our results demonstrate that IL-8 and GRO-alpha are important inflammatory mediators that stimulate the directional migration and recruitment of B lymphocytes. The migratory behavior and the expression of IL-8R on HIV-B cells and some of the reactions to Th1- and Th2-like cytokines are modified significantly during HIV infection.

Adult↗
PubMed1995

Neopterin and beta 2-microglobulin as serum markers in a placebo-controlled anti-HIV therapy trial.

The purpose of this study was to evaluate the use of the biologic immune activation markers neopterin and beta 2-microglobulin in monitoring human immunodeficiency virus (HIV)-positive patients without acquired immunodeficiency syndrome (AIDS) treated with isoprinosine and placebo. Serum samples obtained at the commencement of study and samples obtained after 24 weeks were available from 277 HIV-positive patients in the Scandinavian multicentre isoprinosine trial. After 24 weeks' treatment, the concentrations of beta 2-microglobulin and neopterin had increased both in the isoprinosine group and the placebo group. However, in the isoprinosine group the relative increase within beta 2-microglobulin was significantly smaller. Within neopterin, the increase from baseline level was small and not significantly different from the change in the placebo group. The beta 2-microglobulin data might reflect a suppressive effect of isoprinosine on the HIV-induced activation of the cellular immune system. Because of the minor changes, there is no real evidence of neopterin and beta 2-microglobulin being valuable as surrogate markers in monitoring therapy effects of isoprinosine.

Adolescent↗
PubMed1995

Evaluation of a method for measurement of intracellular killing of Staphylococcus aureus in human neutrophil granulocytes.

A modified method for measurement of intracellular killing of Staphylococcus aureus in human neutrophil granulocytes is described. After phagocytosis of S. aureus the extracellular bacteria were sufficiently removed by repeated centrifugations and washings of the granulocytes. The optimal conditions for incubation of granulocytes for measurement of intracellular killing were found to be 37 degrees C in the presence of 5% CO2. Under these conditions, stable pH, the viability and the capacity of the granulocytes for superoxide anion generation were preserved. The number of intracellular viable bacteria was determined after lysis of the granulocytes, which should be done in H2O at pH 11 to ensure sufficient cell lysis. The kinetics and individual variation of the intracellular killing are described. The intra- or extracellular location of surviving bacteria was studied. After approximately 8 h incubation we observed intracellular growth of S. aureus followed by lysis of granulocytes and extracellular growth of bacteria. Consequently, the incubation period should not be extended beyond 5 to 8 h when the assay is used to study the effects of antibiotics on intracellular killing.

Adult↗
PubMed1994

[Purulent meningitis at the Marselisborg Hospital 1980-1990].

From 1980-1990 245 immunocompetent patients were admitted to The Department of Infectious Diseases, Marselisborg Hospital with purulent meningitis or meningococcal septicaemia. The clinical diagnosis was established by clinical examination and by neutrophil pleocytosis. The aetiological diagnosis was established by demonstration of bacteria in the cerebrospinal fluid by microscopy or culture and by blood culture. Clinical signs of disseminated intravascular coagulation (DIC) or demonstration of meningococcal antibodies (MAT) in serum were considered diagnostic for meningococcal disease. The group comprised 120 males and 125 females aged 0-90 years. One hundred and eleven (45%) had meningococcal disease, 69 (28%) had pneumococcal meningitis, and 20 (8%) had H. influenzae-meningitis. Other aetiologies occurred in one to six cases. No aetiology could be established in 25 (10%) patients. Patients with meningococcal and pneumococcal disease were treated with monotherapy with high doses of penicillin, and H. influenzae-meningitis was treated with ampicillin. In patients with meningitis of unknown aetiology penicillin was used, except in children below the age of five where ampicillin was used. In patients with meningococcal disease the mortality was 5.4%, and 17% developed sequelae. In pneumococcal meningitis the corresponding figures were 13% and 17%, and in H. influenzae-meningitis 0% and 5% respectively. Among 20 patients with other aetiologies one patient (5%) died, and eight (40%) developed sequelae, whereas one patient (4%) died, and one (4%) developed sequelae in the group with meningitis of unknown aetiology. No ampicillin-resistant H. influenzae-strains were demonstrated. We suggest that monotherapy with betalactam-antibiotics is still a valuable treatment for meningitis in Denmark.

Adult↗