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Biomedical subjects

K Arnold

Publications and source records attributed to K Arnold.

At least 289 records · Page 16Linked to original sources
PubMedDate not supplied

Mechanisms of inhibition of chemiluminescence in the oxidation of luminol by sodium hypochlorite.

Two different mechanisms of inhibition of chemiluminescence in the oxidation of luminol by sodium hypochlorite were found. Most substances investigated in these experiments acted by scavenging NaOCl. This mechanism was independent of the concentration of hydrogen peroxide and the incubation time between luminol and inhibitors. The most potent inhibitors were substances containing SH groups. Compounds with amino groups as a target for HOCl/OCl- to yield chloramines were much less effective inhibitors. Another mechanism of inhibition was found for catalase. It depended on the presence of hydrogen peroxide in the incubation medium and the incubation time between luminol and catalase. The enzyme inhibited the luminescence by removing H2O2 at molar concentrations much smaller than those found for all other inhibitors. Our results confirm the present models of the mechanism of generation of luminescence in luminal oxidation.

Kinetics↗
PubMedDate not supplied

Increased native chemiluminescence in granulocytes isolated from synovial fluid and peripheral blood of patients with rheumatoid arthritis.

Polymorphonuclear leukocytes (PMNs) isolated from peripheral blood and synovial fluid of patients with rheumatoid arthritis and from peripheral blood of volunteers were stimulated with 12-phorbol-13-myristate acetate (PMA). No significant differences in luminol-amplified chemiluminescence were found between different patients and control groups. However, two distinct patterns of native chemiluminescence were observed. Type I showed no, or only a small, increase in native chemiluminescence with integral counts over 30 min less than 3 x 10(5) cpm, and the majority of samples from volunteers were of this type. Type II was characterized by a burst of native chemiluminescence starting 8 to 15 min after cell stimulation. It was found in most PMN samples from patients with rheumatoid arthritis. Integral counts over 30 min were always higher than 10(6) cpm and as high as 10(8) cpm in some cases. A strong inhibition of the Type II native chemiluminescence was caused by desferal, catalase, thiourea, and glutathione. However, the luminol-amplified chemiluminescence remained unchanged or was only slightly decreased under the same experimental conditions. Sodium azide strongly inhibited both kinds of luminescence. Hydroxyl radicals, formed in a Fenton reaction, may be important intermediates in the Type II native chemiluminescence.

Arthritis, Rheumatoid↗
PubMedDate not supplied

A randomized comparative study of artemisinine (qinghaosu) suppositories and oral quinine in acute falciparum malaria.

In adult patients with acute falciparum malaria in Ho Chi Minh City, Vietnam, a more rapid reduction in parasite count (50% clearance in 11.3 h) and complete clearance (41.8 h) was obtained in 32 adult patients randomly assigned to received artemisinine suppositories than was obtained with 30 patients receiving oral quinine (20.8 h and 68.1 h). There were higher degrees of resistance (RII, 3 cases; RI early, 1 case) with quinine than with artemisinine but in a subgroup of patients quinine reduced parasitaemia as rapidly as artemisinine (50% clearance 13.6 h and 10.1 h respectively). Recrudescence (RI, delayed), occurred in 16 patients receiving artemisinine compared with 6 receiving quinine. Artemisinine suppositories, because of ease of administration, efficacy, and lack of side effects or risk of overdose, have advantages for the early treatment of falciparum malaria by possibly reducing the morbidity and mortality associated with a high or sustained parasitaemia.

Acute Disease↗
PubMedDate not supplied

Double-blind studies with mefloquine alone and in combination with sulfadoxine-pyrimethamine in 120 adults and 120 children with falciparum malaria in Vietnam.

In 120 adult Vietnamese patients with uncomplicated falciparum malaria the efficacy of, and tolerance to, mefloquine (M) vs the combination of mefloquine + sulfadoxine + pyrimethamine (MSP) was studied in a double-blind, randomized comparative trial with chloroquine. Also, a double-blind dose finding study of MSP was performed in 120 Vietnamese children with uncomplicated falciparum malaria. In the adults the mean parasite clearance time with M was 3.8 d and with MSP 3.6 d. Defervescence occurred in 2.9 and 3.0 d respectively for M and MSP. There was a 36.8% resistance rate in 38 patients treated with chloroquine. 96% of the children were sensitive or showed a delayed RI response. The lowest dose of MSP (10 mg/kg M + 20 mg/kg S + 1.0 mg/kg P, 1 tablet Fansimef) was as effective as 1.5-2x this dose in children weighing 23-30 kg. Side effects were mild, except for vomiting which required alternative therapy in 4 patients.

Adolescent↗
PubMedDate not supplied

Comparison of artemisinin suppositories with intravenous artesunate and intravenous quinine in the treatment of cerebral malaria.

Seventy-nine comatose cerebral malaria patients given standard supportive treatment were randomized to receive specific antimalarial chemotherapy of intravenous quinine, intravenous artesunate, or artemisinin suppositories. Artesunate and artemisinin reduced peripheral asexual parasitaemia significantly more rapidly than quinine (90% clearance time 16 h, 18.9 h and 34.5 h respectively), but did not significantly reduce the duration of coma or mortality. The rapid lowering of peripheral parasitaemia may not ameliorate complications already present. These results demonstrate that artemisinin suppositories are as effective as artesunate and quinine given intravenously, and have economic and practical advantages for the treatment of severe malaria in areas remote from major medical centres. However, large numbers of patients will need to be studied if differences in mortality between the 3 treatment groups are to be demonstrated.

Adolescent↗
PubMedDate not supplied

Single dose artemisinin-mefloquine treatment for acute uncomplicated falciparum malaria.

For the treatment of patients with acute falciparum malaria, the combination of artemisinin as a single dose with a single dose of mefloquine was studied in 4 separate prospective trials, comprising 405 adults and 139 children with uncomplicated falciparum malaria in 2 in-patient and 2 rural out-patient studies in Viet Nam. Adults received oral artemisinin and children artemisinin suppositories. Randomized comparative treatment schedules were: artemisinin alone for 5 d, mefloquine-sulfadoxine-pyrimethamine (MSP), or quinine plus sulfadoxine-pyrimethamine (SP). Parasite clearance times (PCT) were rapid for artemisinin treated inpatients (90%: 14.8-20.4 h) but also for patients receiving MSP (PCT 90%: 18.0 h) and quinine (PCT 90%: 22.5 h). The recrudescence rate (RI) during a 28 d follow-up period among the patients given artemisinin plus mefloquine was 15% in the adult in-patients and zero in the adult and children out-patients. RI in the artemisinin 5 d treatment group was 33.3%; among those given artemisinin plus SP it was 47.3% in in-patients and in out-patients 46.1%. In the MSP treated out-patients RI was 1.5% in adults and zero in children. Artemisinin as a single dose (oral in adults and as a suppository in children) in combination with mefloquine was effective in rapidly lowering parasitaemia and in preventing recrudescence in hospital in-patients and in out-patients attending a rural health clinic. MSP alone as a single dose also rapidly reduced parasitaemia (but not as quickly as the artemisinin-mefloquine combination in out-patient children) and prevented recrudescence.

Acute Disease↗
PubMedDate not supplied

Severe and complicated malaria treated with artemisinin, artesunate or artemether in Viet Nam.

One hundred and seventy five Vietnamese adults with severe and complicated malaria admitted to a rural district hospital were entered into an open randomized comparative study to compare 4 treatment regimens based on artemisinin and its derivatives. The median time of defervescence was 48 h (95% confident interval [CI] 38-58 h) in those given intramuscular (i.m.) artemether, 42 h (95% CI 36-48 h) in those given artemisinin suppositories, 36 h (95% CI 30-42 h) in those receiving artesunate (i.m.) and 30 h (95% CI 18-42 h) in those receiving intravenous artesunate (P = 0.13). The respective median parasite clearance times were 30 h (95% CI 26-34 h), 30 h (95% CI 24-36 h), 24 h (95% CI 15-33 h), and 24 h (95% CI 15-33 h) (P = 0.30); the median times for recovery of consciousness were 47 h (95% CI 31-63 h), 24 h (95% CI 18-30 h), 30 h (95% CI 18-42 h), and 24 h (95% CI 4-44 h) (P = 0.18); and the mortality rates were 11.1%, 17.6%, 10.2% and 16.6%, respectively (P = 0.64). There was no significant difference in efficacy between the 4 treatments.

Adolescent↗
PubMedDate not supplied

Platelet secretory products inhibit lipoprotein metabolism in macrophages.

Macrophages possess a receptor that binds low-density lipoproteins (LDL) containing lysine residues modified by acetylation (Ac LDL), acetoacetylation (AcAc LDL) or malondialdehyde treatment. This receptor (referred to as the Ac LDL receptor or scavenger receptor) internalizes the bound lipoprotein. As a consequence, massive amounts of cholesteryl esters accumulate so that macrophages in culture resemble foam cells found in atherosclerotic lesions. In an effort to identify an unmodified mammalian macromolecule that binds to the Ac LDL receptor, we investigated whether platelet secretory products affect the receptor-mediated endocytosis of chemically modified lipoproteins. Platelets are a potential source of such activity because they exist in close association with foam cells in developing atherosclerotic lesions. Our study demonstrates that human blood platelets secrete a product that inhibits the binding and uptake of AcAc LDL by mouse peritoneal macrophages and the subsequent accumulation of cholesteryl esters. This is the first indication that an endogenous macromolecule interacts with Ac LDL receptor on macrophages.

Animals↗
PubMedDate not supplied

Response of typhoid fever caused by chloramphenicol-susceptible and chloramphenicol-resistant strains of Salmonella typhi to treatment with trimethoprim-sulfamethoxazole.

Chloramphenicol remains the drug of choice for the treatment of typhoid fever in most areas despite the risks of relapses and toxicity. In a comparison of the efficacy of trimethoprim-sulfamethoxazole (TMP-SMZ) and chloramphenicol against typhoid fever, 60 patients in Indonesia were randomly assigned to receive either TMP-SMZ (320 mg of TMP and 1,600 mg of SMZ daily) or chloramphenicol (2 g daily) for 14 days. TMP-SMZ was significantly more effective in sterilizing the blood, but the two drugs were equally effective with regard to relapse rate, frequency of prolonged fever, and mortality. Use of TMP-SMZ in Vietnam for the treatment of typhoid fever caused by chloramphenicol-resistant Salmonella typhi showed that TMP-SMZ is as effective as ampicillin. Likewise, a review of other published reports suggests that TMP-SMZ has an overall record in the treatment of typhoid fever that is equal to or better than the records of other available drugs. TMP-SMZ has emerged as a satisfactory alternative to chloramphenicol for the treatment of typhoid fever and should be especially useful in areas where chloramphenicol-resistant S. typhi has been isolated.

Adolescent↗
PubMedDate not supplied

The Bayer-Activities of Daily Living Scale (B-ADL): results from a validation study in three European countries.

The Bayer-Activities of Daily Living Scale (B-ADL) is a 25-item, informant-rated questionnaire which was developed as a brief and internationally applicable instrument for assessing functional disabilities. The scale's target group are elderly patients suffering from mild to moderate dementia or cognitive impairment. To investigate the reliability and validity of different language versions, the B-ADL was administered in the UK, Germany, and Spain to a total of 1,433 subjects with a wide range of cognitive decline. The results from the three country samples were very similar, with internal consistency being above 0.98 (Cronbach alpha). A factor analysis revealed that a one-factor solution accounted for most of the variance. The B-ADL total score significantly increased between adjacent Global Deterioration Scale (GDS) stages 1 to 5. A second factor analysis entering additional variables (GDS stage, Mini-Mental State Examination or MMSE subscores, age, years of education, gender, and country) revealed that all B-ADL items loaded on the same factor, "dementia severity", and that they were not related to age, education, gender, or country. In the identification of subjects with clinically manifest dementia symptoms (GDS stages 4 and 5), the B-ADL proved to be as efficient as the MMSE in the UK and German samples and superior to the MMSE in the Spanish sample.

Activities of Daily Living↗
PubMedDate not supplied

[The effect of temperature on preservation of swine articular cartilage--an NMR study].

The influence of temperature on stored porcine articular cartilage was studied and the factors underlying degradation identified. For these investigations, specimens measuring 18 mm in diameter were punched out of the articularis humeri of juvenile pigs. These samples were investigated by MR microimaging immediately after preparation, and after storage for three days at +4 degrees C and -18 degrees C. Five smaller (3 mm) cylindrical specimens were then obtained and compared with one another using MR-spectroscopy, relaxometry and biochemical assays. From the experiments we conclude that all analytical methods--with the exception of MR microimaging--are capable of detecting changes in cartilage, and that it is not advisable to keep cartilage frozen, since marked changes, presumably at the cellular level, occur. Storage at +4 degrees C also requires the use of preserving chemicals, as otherwise, the polymers of the extracellular matrix degrade.

Animals↗
PubMedDate not supplied

Action of hypochlorous acid on polymeric components of cartilage. Use of 13C NMR spectroscopy.

It is a well known fact that neutrophil-derived hypochlorous acid plays an important role in cartilage destruction during rheumatoid arthritis. It has been shown by 1H NMR spectroscopy in a previous paper (Schiller et al. (1994), Biol. Chem. Hoppe-Seyler 375, 167-172) that sodium hypochlorite affects primarily the N-acetyl side chains of polymeric carbohydrates of cartilage like chondroitinsulphate and hyaluronic acid. An instable intermediate, likely to be a chloramine, is involved in these processes. The present paper deals with the application of carbon NMR spectroscopy for the study of these degradation processes, because carbon NMR gives the opportunity to detect changes on the single sugar ring carbons. Although it was not possible to prove the involvement of an intermediate, because of its fast hydrolysis, we were able to show that the reaction between sodium hypochlorite and N-acetylglucosamine affects mainly the side chain, accompanied by the formation of acetate. The application of a large excess of sodium hypochlorite leads to a breakdown of the carbohydrate ring under the formation of formiate.

Acetylgalactosamine↗
PubMedDate not supplied

Reaction of hypochlorous acid with bovine nasal cartilage comparison to pig articular cartilage.

The action of sodium hypochlorite (NaOCl) on bovine nasal cartilage was studied by proton nuclear magnetic resonance (1H-NMR) spectroscopy in order to model degradation processes of cartilage caused by neutrophil-derived hypochlorous acid. Nasal cartilage was chosen as a mean of comparison because it differs from articular cartilage in its composition. It contains some more proteoglycans, i.e. polymeric carbohydrates and less collagen than articular cartilage. This is important for studying the influence of hypochlorous acid on cartilage components (collagen and polysaccharides). Cartilage samples were incubated at 37 degrees C with phosphate buffer in the presence or absence of NaOCl. Supernatants were collected and assayed by NMR-spectroscopy. In the presence of pure phosphate buffer, the supernatants of bovine nasal cartilage were less rich in low molecular mass metabolites (e.g. amino acids, lactate) than articular cartilage. However, intense signals for highly mobile N acetyl groups of cartilage polysaccharides were detectable in nasal cartilage. NaOCl caused an increase in signals for acetate and formiate. Signals for N-acetyl groups rose only during the first 25 minutes of incubation with NaOCl. Then, their concentration decreased markedly. These changes were related to an enhanced release of chondroitinsulfate from nasal cartilage.

Animals↗
PubMedDate not supplied

Nuclear magnetic resonance and mass spectrometric studies on the action of proteases on pig articular cartilage.

Rheumatic diseases are accompanied by a progradient diminution of the cartilage layer. Unfortunately, degradation mechanisms (role of different enzymes and reactive oxygen species) are not yet understood. Since nuclear magnetic resonance (NMR) spectroscopy was often used for the investigation of synovial fluids, the aim of the present work was to detect cartilage degradation products upon proteolytic digest of cartilage. Cartilage samples were incubated at 37 degrees C with phosphate buffer in the absence or presence of different proteases (collagenase, trypsin and papain). Supernatants were subsequently assayed towards their content of carbohydrate and protein degradation products by NMR (1H- and 13C-) and MALDI-TOF mass spectrometry. Intense resonances of relatively mobile N-acetyl side chains (ca. 2.01 ppm) of polysaccharides of cartilage were only detectable on digestion with papain. The appearance of these resonances indicates intense degradation of the core protein of proteoglycan aggregate of cartilage, whereby polysaccharides are released. Additionally, broad resonances at 0.85 ppm arising from collagen degradation products were observed upon the action of all applied proteases. However, glycine as a marker of exhaustive collagen degradation was only observed, if cartilage was digested by collagenase. Using more vigorous incubation conditions, additionally high-abundant amino acids of collagen (proline, hydroxyproline) could be detected in the 13C-NMR- and the MALDI spectra. The observed differences are correlated with the different selectivities of the applied enzymes. It is concluded that NMR allows the detection of characteristic protein and polysaccharide degradation products. The observed differences may be of some relevance for the diagnosis of rheumatic diseases.

Animals↗
PubMedDate not supplied

[Cognitive and activity-oriented processes in the rehabilitation of elderly stroke patients].

Investigated were 12 aged stroke patients during and one-half year after treatment in hospital; interviews are compared with regard to stress, competence, and coping. The analysis shows that patients become aware of multiple restrictions after their release from hospital. We pointed out that rehabilitation should concentrate more strongly on normal life demands of the patients as well as on their psycho-social resources. A survey of some of the typical coping strategies is included, which could be considered during the rehabilitation process.

Activities of Daily Living↗