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Biomedical subjects

A Waldner

Publications and source records attributed to A Waldner.

At least 19 recordsLinked to original sources

[Should NSAID/corticoids be considered when treating erysipelas?].

Using non-steroidal anti-inflammatory drugs (NSAID) in association with a suitable antibiotherapy in the treatment of erysipelas, is still being largely discussed in medical publications. When compared to other fields of medicine, here their use might be justified by their ability to reduce local inflammation processes, to relieve patients more quickly, and to prevent potential sequels due to an inflammatory process. Numerous reports have suggested an association between the use of NSAID and the progression of an invasive streptococcal infection, particularly necrotizing fasciitis. The exact mechanism is still unclear. No controlled survey (NSAID versus placebo) checking the efficiency and the safety of these treatments is currently available. Only one comparative study showed a gain of one single day for prednisolone The prednisolone-treated patients had a shorter median length of hospital stay (5 days vs. 6) than the placebo-treated ones. The median treatment time with intravenous antibiotics, in the placebo group, was 1 day longer than in the prednisolone group. The occurrence of side effects was not higher in the prednisolone group. If this currently available data is not sufficient to establish a relationship between severe infectious complications and the use of NSAID, one should be cautious when using them to treat erysipelas, since their efficiency has not been positively proved.

Adrenal Cortex Hormones↗

[Discontinuing protease inhibitor treatment of HIV-1 patients for intolerance. Longitudinal study of 309 patients].

OBJECTIVES: Determine the frequency and nature of interruptions in HIV-1 protease inhibitor treatment in HIV-infected patients. PATIENTS AND METHODS: A longitudinal study included patients treated with antiretroviral protocols including at least one antiprotease and followed from 1 March 1996 through 1 March 1998. RESULTS: Among the 309 patients followed for the duration of the study, 137 (44.3%) interrupted their antiprotease treatment at least once. Withdrawal was warranted by therapeutic failure in 49.6% of the cases and by drug intolerance in 45.4%. Drug intolerance concerned 37%, 36.7%, 5.7% and 2.9% of the patients taking ritonavir, indinavir, nelfinavir and saquinavir respectively (p < 106). Multivariate analysis demonstrated that saquinavir was significantly associated with better tolerance and with efficacy at least as good as ritonavir or indinavir. The most frequent cause for interrupting treatment were digestive disorders for ritonavir (20% of the treated patients) and lithiasic manifestations for indinavir (9.4%). The ritonavir-hepatitis C association appeared to predispose to drug-induced perturbed liver tests. CONCLUSION: Drug intolerance is a frequent cause of treatment interruption. Therapeutic success in HIV infection requires improved efficacy but also better tolerated antiretorviral drugs, particularly antiretroviral drugs.

Adult↗

The Swedish version of the Bath ankylosing spondylitis functional index. Reliability and validity.

The aim of the study was to investigate the reliability and the validity of the Swedish version of the Bath Ankylosing Spondylitis Functional Index (BASFI). A total of 113 patients were assessed with the BASFI, the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), the Bath Ankylosing Spondylitis Metrology Index (BASMI), and the Bath Ankylosing Spondylitis Patient Global Score (BAS-G). The median BASFI scores on two occasions within 24 hours were 3.6 versus 3.7 (p>0.05). The patients found the BASFI items relevant. The median self-reported and physiotherapist-observed BASFI scores were 3.4 and 2.8 respectively (p>0.05). The correlation coefficient between the BASFI and the BASMI was r(s)=0.55, between the BASFI and the BASDAI r(s)=0.68, and between the BASFI and the BAS-G r(s)=0.67. Significant improvements between the pre- and post-training results for both the BASFI (3.1 vs 2.0, p<0.001) and the BASMI (3.0 vs 1.0, p<0.001) were found after three weeks' inpatient rehabilitation. The results indicated that the Swedish BASFI is reliable and valid.

Adult↗

The Swedish version of the Bath ankylosing spondylitis disease activity index. Reliability and validity.

The aim of the study was to investigate the reliability and the validity of the Swedish version of the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI). A total of 113 patients with ankylosing spondylitis were assessed with the BASDAI, the Swedish version of the Bath Ankylosing Spondylitis Functional Index (BASFI), the Bath Ankylosing Spondylitis Metrology Index (BASMI), the Bath Ankylosing Spondylitis Patient Global Score (BAS-G), and a questionnaire on their opinions of the relevance of the BASDAI. The test-retest stability investigation of the BASDAI over 24 hours did not show any difference between the two occasions (md 4.4, range 0.80-8.43 vs md 4.0, range 0-7.80, p > 0.05). The correlation coefficient between the BASDAI and the BASMI was r(s) = 0.07, between the BASDAI and the BASFI r(s) = 0.64, and between the BASDAI and the BAS-G r(s) = 0.80. Eighty percent of the patients considered the contents of the BASDAI to be relevant. The BASDAI, the BAS-G and the BASMI showed significant improvements after an intensive rehabilitation period. In conclusion the results of the present study indicate that the Swedish BASDAI is reliable and valid.

Adult↗

Does hepatitis C virus co-infection accelerate clinical and immunological evolution of HIV-infected patients?

OBJECTIVE: To study the influence of hepatitis C virus (HCV) co-infection on clinical and immunological evolution of HIV-infected patients. DESIGN: A longitudinal study of HIV-infected individuals with or without HCV infection, identified at the Infectious Diseases Department of Dijon University Hospital and enrolled in a historical cohort, was performed. METHODS: One hundred and nineteen HIV-infected people co-infected with HCV and 119 matched individuals infected with HIV alone were included in the cohort (median participation time 3 years; range, 2 months to 11.5 years). Clinical progression was defined as one or more of the following: a 30% decrease in the Karnofsky index; a 20% loss of body weight; an AIDS-defining illness (for non-AIDS patients); death (except by accident, suicide or overdose). Immunological progression was defined as a 50% decrease in the initial CD4 T-cell count (for patients with an initial count > 100 x 10(6) cells/l). Effects of HCV co-infection were evaluated using Kaplan-Meier survival analysis and significance was tested using univariate (log-rank and Peto's tests) and multivariate methods (Cox's model). RESULTS: In univariate analysis, immunological progression was not statistically different between the HCV-positive group and the HCV-negative group, whereas clinical progression was significantly faster in HCV-positive patients (P < 0.005, log-rank test). In a multivariate Cox model, clinical progression remained significantly associated with infection by HCV [hazard ratio (HR), 1.64; 95% confidence interval (CI), 1.06-2.55; P < 0.05]. Stratified multivariable analysis retained HCV as a significant prognostic factor of clinical progression (HR, 10.9; 95% CI, 1.09-109.3; P < 0.05) and immunological progression (HR, 2.31; 95% CI, 1.16-4.62; P < 0.02) for patients with an initial CD4 count above 600 x 10(6) cells/l. CONCLUSIONS: Clinical progression is more rapid in HIV-HCV co-infected patients than in HIV-seropositive patients are not infected by HCV. The prognostic value of HCV infection for both clinical and immunological progression is significant at early stages of HIV infection. These findings may argue for active management of hepatitis C infection in co-infected individuals, especially for asymptomatic patients whose CD4 count is above 600 x 10(6) cells/l, to predict and prevent accelerated progression of HCV and HIV diseases.

Adult↗

All-solid-state miniaturized fluorescence sensor array for the determination of critical gases and electrolytes in blood.

We describe a six-channel, all-solid-state, miniaturized fluorescence sensor array for the precise determination of blood analytes for medical diagnostic purposes. The device features superblue LEDs as light sources, GRIN optics, and photodiodes, assembled according to pigtailing procedures (Bruno, A. E.; et al. Trends Anal. Chem. 1994, 13, 190-198). The numerical aperture of the fluorescence optics is 0.46, rendering a collection efficiency of 2.4%. The performance of this instrument has been evaluated in terms of dynamic response, linearity, channel reproducibility, reversibility, long-term drifts, photobleaching of indicator, cross-talk, ionic strength, and selectivity in pH measurements. The responses of the pH sensing membranes were optimized in the physiological range. Responses are linear with typical values of approximately 1.5 V/pH units, with limits of decision of 24 mV, which corresponds to pH resolutions of 0.03 pH unit. Under continuous illumination, using calibration buffers, the sensors display nonstatistical differences within 2 standard deviations over a period of 6 h, and it is shown that, under discontinuous illumination, the membranes can be used in more than 2000 measurements without need of calibration, in contrast to electrochemical sensors which require periodic calibration. After selecting the appropriate combination of LEDs, excitation and emission filters, and sensing membranes, the instrument was used to determine the concentrations of various critical blood analytes in buffer solutions in the various channels. Similar measurements in untreated blood reproduce the reported results.

Biosensing Techniques↗

Backbone modifications in oligonucleotides and peptide nucleic acid systems.

In the past year major advances have been made in the design, synthesis and characterization of two classes of modified oligonucleotides. In the first class, the phosphodiester backbone of 2'-deoxyribo-oligonucleotides has been replaced in several different ways. The second group represents a completely different type of oligonucleotide modification in which the backbone and the 2'-deoxyribose moieties are replaced by amino acids. These advances present new possibilities for the pharmaceutical applications of modified oligonucleotides in antisense strategies.

Animals↗

Molecular mechanics and dynamics studies on two structurally related amide-modified DNA backbones for antisense technology.

The effect of the replacement of the natural phosphodiester linkage -C3'-O-PO2-O-CH2-C4'- in the DNA strand of RNA.DNA hybrid duplexes by either of the two amide linkages -C3'-CH2-CO-NH-CH2-C4'- or -C3'-CH2-NH-CO-CH2-C4' has been investigated by molecular mechanics (MM) and molecular dynamics (MD) simulations. Conformational analysis has been used to assess various low-energy conformers of the amide-modified backbones. MD simulations have been carried out to study the dynamic behavior of the modified duplexes. The modified RNA.DNA hybrid double helices kept a conservative base pairing scheme during the MD simulations. Although the general behavior has been found to be similar to that of the corresponding wild-type hybrid duplexes, some notable differences, especially regarding the sugar puckering in the amide-modified DNA strands, have been observed. The behavior of the RNA strands in the hybrid duplexes has not been affected by the modified DNA strands and is similar to that in wild-type RNA.DNA duplexes.

Amides↗

Cross-sectional study of the susceptibility of Candida isolates to antifungal drugs and in vitro-in vivo correlation in HIV-infected patients.

OBJECTIVES: To investigate (1) the frequency of clinical resistance to oral polyenes or azole treatment for oral candidiasis, (2) the frequency of resistant in vitro Candida strains, (3) the relationship between the susceptibilities of in vitro Candida species and in vivo status in HIV patients. DESIGN: Prospective cross-sectional study. SETTING: Tertiary care clinic at Bocage Hospital, Dijon, France. PATIENTS: HIV-infected patients with and without oral candidiasis. INTERVENTIONS: Clinical examination, oral swab for mycologic investigations. MAIN OUTCOME MEASURES: Clinical diagnosis of oral candidiasis, identification of the antifungal treatment given within the previous month, identification of Candida species, antimycogramm and determination of the minimal inhibitory concentration (MIC) for fluconazole, and measurement of T-helper cell count. RESULTS: Within a 2-month period, 154 HIV-infected patients were studied: 46 heterosexuals, 51 intravenous drug users (IVDU), 52 homosexuals and five blood transfusion recipients. The percentages of patients with oral candidiasis were: 41, 80, 44 and 20%, respectively (P < 0.05); the mean T-helper cell counts were 200, 135, 210 and 238 x 10(6)/l cells, respectively (P < 0.05). Twenty-two patients (14.3%) had received recent azole treatment and 29 (18.8%) recent oral polyene treatment. Among the 84 patients with and the 70 patients without oral candidiasis, 78 and 28 Candida strains were isolated, respectively. Although Candida albicans represented the majority of Candida species (88 strains, 83%), the non-albicans strains were isolated more frequently in patients who had received recent antifungal treatment. No strains were resistant to ketoconazole, miconazole or econazole; however, six (5.6%), 16 (15%) and 10 (9.5%) were intermediately susceptible to the three drugs, respectively. Twelve (13.6%) of the 88 C. albicans, five of the six C. (Torulopsis) glabrata, one of the five C. tropicalis and all three C. krusei strains were resistant to fluconazole. These resistant strains were separated as follows: 41.1% of C. albicans strains resistant to fluconazole were isolated from patients who had received recent azole therapy, 17.6% from patients who received recent oral polyene, and 3.7% from patients who had not received any recent antifungal treatment (P = 0.004). The mean MIC of these three categories of isolates were 3.6, 1.6 and 0.6 mg/l, respectively (P = 0.06). CONCLUSIONS: Oral candidiasis and fluconazole-resistant Candida isolates are more frequently found in IVDU. Treatments using azoles select non-albicans strains and are associated with decreased susceptibilities of C. albicans strains to fluconazole in particular. These findings show that prolonged azole treatment in severely immunocompromised patients should be avoided.

AIDS-Related Opportunistic Infections↗

High concentrations of intrathecal interleukin-6 in human bacterial and nonbacterial meningitis.

Interleukin-6 (IL-6) is multipotent cytokine that acts in a network of factors directing the inflammatory reaction of purulent bacterial meningitis (PBM). However, little is known about the role of IL-6 in aseptic or "viral" meningitis (AM). IL-6 was assayed by RIA in cerebrospinal fluid (CSF) and serum samples obtained from patients with AM (n = 65), PBM (n = 8), and lymphocytic bacterial meningitis (LBM, n = 11). Of patients with AM, 89% had detectable IL-6 in CSF, with high IL-6 titers (median, 2160 pg/mL; 95% confidence interval [CI], 1320-2540 pg/mL) compared with 100% in patients with PBM (median, 6575 pg/mL; 95% CI, 450-32,000 pg/mL) and 90.9% in patients with LBM (median, 875 pg/mL; 95% CI, 150-2180 pg/mL). There was a highly symmetrical correlation between IL-6 and the percentage of polymorphonuclear cells in CSF of patients with PBM (r = .97, P = .01) and AM (r = .49, P = .002). In conclusion, this study shows evidence that IL-6 is released into the meningeal space in aseptic meningitis and is correlated with the local acute inflammatory response.

Humans↗

Bone marrow necrosis and human parvovirus associated infection preceding an Ph1+ acute lymphoblastic leukemia.

A case of bone marrow necrosis associated with a serologically documented recent Parvovirus B 19 infection which preceded the development of PH1+ acute lymphoblastic leukemia is reported. No conclusions can be drawn on the basis of a single case but the question of the role of human Parvovirus B19 in the pathogenesis of bone marrow necrosis is discussed. It is suggested that the virus may act as a co-factor for the induction of bone marrow necrosis, in some cases.

Adult↗

[Emulsion of amphotericin B in Intralipid 20%: in vitro and in vivo efficacy].

Toxic effects limit the use of amphotericin B (AmB) for the treatment of systemic Candida infections. In vitro and in vivo toxicity can be substantially reduced by mixing AmB with a lipid emulsion used for parenteral nutrition, intralipid 20% (IL). This study was designed to evaluate the potential effects of IL on the activity of Amphotericin B against Candida. A clinical strain of Candida albicans was used. AmB deoxycholate (Fungizone) was reconstituted in a 5% glucoce solution (AmB-G5), in 3 mg/ml IL (AmB-IL3) or in 1.5 mg/ml IL (AmB-IL 1.5). Minimum inhibitory concentrations and minimum lethal concentrations were 0.4 mg/l and 2.5 mg/l, respectively, with AmB-G5, 0.1 mg/l and 1 mg/l with AmB-IL3, and 0.24 mg/l and 1 mg/l with AmB-IL 1.5. In vitro killing curves with 0.1 mg/l, 0.25 mg/l, and 2.5 mg/l AmB were determined with the following results: 1) with 0.1 and 0.25 mg/l AmB, fungicidal activity was seen with AmB-IL3 and AmB-IL 1.5 but not with AmB-G5; 2) with 2.5 mg/l AmB, fungicidal activity was less marked with AmB-G5 (-1.7 log CFU/ml after 24 hours) than with AmB-IL3 and AmB-IL1.5 (-4.3 log CFU/ml and -4.2 log CFU/ml, respectively, after 24 hours; p less than 0.05). In rabbits given a single intravenous injection of 4 mg/kg AmB, analysis of infected subcutaneous fibrin clots detected measurable concentrations of AmB beyond the 24th-36th hour, with levels of 0.5 mg/l for AmB-G5 and 1 mg/l for the two AmB-IL preparations over a period of three days.(ABSTRACT TRUNCATED AT 250 WORDS)

Amphotericin B↗

Synergism between cefotaxime and fosfomycin in the therapy of methicillin and gentamicin resistant Staphylococcus aureus infection in rabbits.

An experimental model of infected subcutaneous fibrin clots in rabbits was used to study the synergism between cefotaxime and fosfomycin in infection with methicillin and gentamicin resistant Staphylococcus aureus (MGRSA), and to determine the efficacy of a simplified schedule of administration. The bactericidal activity of cefotaxime and fosfomycin against MGRSA was investigated giving the drugs in one full or two divided doses either alone or in combination. The pharmacokinetics of the drugs were correlated with the antibacterial efficacy obtained over 12 hours of treatment. The results confirmed that the combination of cefotaxime and fosfomycin is highly synergistic in experimental MGRSA infection. Higher bactericidal activity was obtained with a regimen of 6-hourly drug administration which resulted in persistent levels of both drugs in serum as well as at the site of infection.

Analysis of Variance↗

A double-blind randomized placebo trial on very high doses of acyclovir in weakly symptomatic HIV-patients.

Herpesvirus infections are thought to be cofactors of the human immunodeficiency virus (HIV) disease, and high concentrations of acyclovir (ACV) are active on all herpesviruses. Because ACV was shown to delay the cytopathic effect of HIV in vitro, we evaluated the effect of intermittent high doses of ACV in mildly symptomatic HIV-patients in a randomized double-blind placebo-controlled trial with a 4-month treatment period. A total of 30 CDC II and III patients were enrolled; 24 (80%) completed the study. Placebo and ACV were given once a week in a 3-h infusion with 1 g oral probenecid. Each dose of ACV was 50 mg/kg. Pharmacokinetic data were obtained from patients of the preliminary open study. The obtained concentrations were effective against both herpesviruses and HIV: peak concentrations were 197 and 11 mumol/l in serum and CSF, respectively; the CSF:serum ratio of the areas under the curve was 82%. Two patients with placebo acquired hairy leukoplakia and detectable antigenemia vs. none in the ACV group (p = 0.23). T-helper cell count over the 4-month period decreased in the placebo group while it increased in the ACV-treated group (mean of change = -105 c/microliters vs. +68 c/microliters; p = 0.06). beta 2-microglobulin increased with placebo and did not with ACV (mean of change = +0.63 mg/l vs. -0.27 mg/l, p less than 0.025). Only one patient had, at one time, transient elevation of creatinemia related to ACV. We concluded that weekly high doses of ACV were able to delay the progression of some significant markers of HIV disease. Thus, preventive/prophylactic treatment of herpesvirus infections could be useful in mildly symptomatic HIV patients. Further larger trials using a more feasible treatment are warranted.

Acyclovir↗