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Biomedical subjects

J Brandt

Publications and source records attributed to J Brandt.

At least 91 records · Page 5Linked to original sources

Treatment of active ankylosing spondylitis with infliximab: a randomised controlled multicentre trial.

UNLABELLED: BACKGROUND Treatment options for patients with ankylosing spondylitis are few. We aimed to assess the effectiveness of infliximab, an antibody to tumour necrosis factor (TNF)-alpha, in treatment of such patients. METHODS: In this 12-week placebo-controlled multicentre study, we randomly assigned 35 patients with active ankylosing spondylitis to intravenous infliximab (5 mg/kg) and 35 to placebo at weeks 0, 2, and 6. One patient in the infliximab group was withdrawn from the study. Our primary outcome was regression of disease activity of at least 50%. To assess response, we used validated clinical criteria from the ankylosing spondylitis assessment working group, including disease activity (BASDAI), functional indices (BASFI), metrology (BASMI), and quality of life (short form 36). Analyses were done by intention to treat. FINDINGS: 18 (53%) of 34 patients on infliximab had a regression of disease activity at week 12 of at least 50% compared with three (9%) of 35 on placebo (difference 44% [95% CI 23-61], p<0.0001). Function and quality of life also improved significantly on infliximab but not on placebo (p<0.0001 and p<0.0001, respectively). Treatment with infliximab was generally well tolerated, but three patients had to stop treatment because of systemic tuberculosis, allergic granulomatosis of the lung, or mild leucopenia. INTERPRETATION: Our results show that treatment with infliximab is effective in patients with active ankylosing spondylitis. Since there are some potentially serious adverse effects, we recommend that this treatment mainly be used in co-operation with rheumatological centres.

Adult↗

Survey for Trichinella spp. in red foxes (Vulpes vulpes) in Belgium.

Concurrently with a survey for Echinococcus multilocularis in the red fox (Vulpes vulpes) in Flanders, northern Belgium, serological and parasitological analyses for Trichinella spp. were carried out from 1996 to 1999. Muscle samples from foxes in Wallonia, southern Belgium, were obtained during a survey for rabies and alveolar echinococcosis from 1998 to 2000. In muscle samples from tongue, diaphragm, hindlegs and tail of 179 Flemish foxes no larvae were found by trichinoscopy. Serum and muscle juice of, respectively 176 and 26 animals were examined using an ELISA for the detection of antibodies against excretory-secretory (ES) antigen. There were eight (4.5%) positive sera, but no positive muscle juice samples. All muscle samples from 639 foxes in Wallonia proved to be negative for larvae in artificial digestion. Serum and muscle juice of 130 and 478 foxes, respectively were examined in ES-ELISA. There were 61 (46.9%) positive sera and 90 (18.8%) positive muscle juice samples. A comparison between 88 serum and muscle juice samples of the same foxes showed that only half of the serum-positive animals were detected using muscle juice. However, for establishing the true meaning of these results, a more profound epidemiological study on the vulpine population in Belgium is necessary.

Animals↗

Distribution and phenology of ixodid ticks in southern Zambia.

Distribution data for epidemiologically important ticks (Acari: Ixodidae) in the Southern Province of Zambia, one of the main cattle areas of the country, are presented. Boophilus microplus (Canestrini) was not recorded in southern Zambia, whereas Boophilus decoloratus (Koch) is present throughout the area. New distribution patterns for less economically important ixodid ticks are also discussed. Southern Zambia is a transition zone because it is the most northern area in Africa where mixed Rhipicephalus appendiculatus Neumann and Rhipicephalus zambeziensis Walker, Norval & Corwin populations were reported. Although a second generation of adult R. appendiculatus/R. zamnbeziensis was encountered, simulations indicated that this phenomenon is very rare in southern Zambia, mainly because of the colder temperatures during the early dry season and lower rainfall. These simulations were supported by a development trial under experimental conditions. Tick body size measurements showed that southern Zambian ticks are larger than eastern Zambian R. appendiculatus. It is hypothesized that body size is related to diapausing intensity in this species. The epidemiological consequences are that a different approach to control Theileria parva (Theiler) (Piroplasmida: Theileriidae) and other tick-borne diseases is needed in southern Zambia, compared to the one adopted in eastern Zambia.

Animals↗

[Taenia solium taeniasis/cysticercosis in the Menoua division (West Cameroon)].

The present study was carried out between August 1999 and April 2000 with the objective of determining the prevalence of Taenia solium taeniasis in two village communities of Bafou and Bamendou in the Menoua division (West Cameroon). Four (0.13%) out of 3,109 faecal samples were positive for Taenia spp. eggs using the flotation technique. Three of the four worms expelled were T. solium whereas the other one was T. saginata. Two cases of cysticercosis were diagnosed in one of the families with a T. solium carrier. Furthermore, coprological and serological investigations for T. solium taeniasis and cysticercosis were carried out among butchers and/or tongue inspectors (n = 137) of the city of Dschang. The results were compared with those of a control group (n = 198). Taenia spp. eggs were not detected by microscopic examination. The prevalence of cysticercosis in the two groups was relatively similar (3.6 and 4.5% respectively).

Animals↗

Improved cardiac function and quality of life following upgrade to dual chamber pacing after long-term ventricular stimulation.

AIMS: Many patients with sinus node disease or atrioventricular block have previously received pacemakers with only ventricular stimulation (VVI or VVIR). This study aimed to investigate whether quality of life and cardiac function were affected by an upgrade to dual chamber pacing (DDDR or DDIR) following long-term ventricular stimulation. METHODS: After implantation of an atrial lead and a DDDR pulse generator, a randomized, double-blind crossover study was performed in 19 patients, previously treated with ventricular pacing for a median time of 6 X 8 years. Patients were randomized to 8 weeks with either VVIR or DDDR/DDIR pacing; after this time, the other mode was programmed for 8 weeks. At the end of each period, the patients' quality of life was evaluated and echocardiography was performed together with Holter monitoring and blood samples for brain natriuretic peptide. RESULTS: Sixteen of the patients preferred DDDR and two VVIR pacing (P=0 X 001); one was undecided. Seven patients demanded an early crossover while paced in the VVIR mode, vs none in the DDDR mode (P=0 X 008). Quality of life was higher in the DDDR mode in 11 of 17 modalities, reaching statistical significance for dyspnoea (P<0 X 05) and general activity (P<0 X 05). Echocardiography showed significantly larger left ventricular end-diastolic dimensions in the DDDR mode (P=0 X 01), whereas end-systolic dimensions did not differ. Left ventricular systolic function was significantly superior in the DDDR mode (mean aortic velocity-time integral: P<0 X 001) and left atrial diameter was significantly smaller in the DDDR mode (P=0 X 01). The plasma level of brain natriuretic peptide was significantly lower in DDDR mode (P=0 X 002). CONCLUSION: An upgrade to dual chamber rate adaptive pacing results in significantly improved quality of life and cardiac function as compared to continued VVIR stimulation and should thus be considered in patients with ventricular pacemakers who have not developed permanent atrial fibrillation or flutter.

Aged↗

Expression of cathepsin B, D and L protein in juvenile idiopathic arthritis.

Juvenile idiopathic arthritis (JIA) is the most common childhood autoimmune rheumatic disease and like rheumatoid arthritis (RA), it is characterized by inflammation and the progressive destruction of joints. In RA, cathepsins as proteinases play a major role in destroying synovial tissue and cartilage matrix. So far no data on cathepsin expression in pannus tissue of HA patients exist. The aim of this study was to characterize the expression levels of cathepsins B, D, H, and L in HA and to compare them with those in RA. Synovectomy tissue from 16 HA and 12 RA patients was investigated for cathepsin expression levels by Western blot analysis. Expression of cathepsins B, D and L was on comparable levels in the synovectomy tissue of HA and RA patients. The following graduation of expression was determined: cathepsin D > cathepsin L > cathepsin B. Cathepsin H was neither found to be expressed in HA nor in RA patients. The expression levels of cathepsins in pannus tissue showed no clear difference between patients with systemic JIA and patients with monoarticular JIA. In summary, the comparable expression of cathepsins B, D and L in RA and JIA synovectomy tissue suggests that they may play a similarly important role in destroying synovial tissue and cartilage matrix in the course of HA and RA.

Adolescent↗

Conventional treatments for ankylosing spondylitis.

Management of ankylosing spondylitis (AS) is challenged by the progressive nature of the disease. To date, no intervention is available that alters the underlying mechanism of inflammation in AS. Currently available conventional treatments are palliative at best, and often fail to control symptoms in the long term. Current drug treatment may perhaps induce a spurious state of "disease remission," which is merely a low level of disease activity. Non-steroidal anti-inflammatory drugs are first line treatment, but over time, the disease often becomes refractory to these agents. Disease modifying antirheumatic drugs are second line treatment and may offer some clinical benefit. However, conclusive evidence of the efficacy of these drugs from large placebo controlled trials is lacking. Additionally, these drugs can cause treatment-limiting adverse effects. Intra-articular corticosteroid injection guided by arthrography, computed tomography, or magnetic resonance imaging is an effective means of reducing inflammatory back pain, but controlled studies are lacking. A controlled study has confirmed moderate but significant efficacy of intravenous bisphosphonate (pamidronate) treatment in patients with AS; further evaluation of bisphosphonate treatment is warranted. Physical therapy and exercise are necessary adjuncts to pharmacotherapy; however, the paucity of controlled data makes it difficult to identify the best way to administer these interventions. Surgical intervention may be required to support severe structural damage. Thus, for patients with AS, the future of successful treatment lies in the development of pharmacological agents capable of both altering the disease course through intervention at sites of disease pathogenesis, and controlling symptoms.

Adrenal Cortex Hormones↗

Comparison of conventional techniques to differentiate between Taenia solium and Taenia saginata and an improved polymerase chain reaction-restriction fragment length polymorphism assay using a mitochondrial 12S rDNA fragment.

Given the constraints of classical diagnostic methods, i.e., morphological and isoenzymatic studies of proglottids, a polymerase chain reaction test complemented with restriction enzyme analysis has been modified by redesigning one of the primers to reduce nonspecific amplifications experienced when using field samples. The use of these new, highly cestode-specific primers and the restriction enzyme Ddel led to the development of a diagnostic assay that clearly distinguishes between Taenia saginata and T. solium proglottids in field samples. This assay confirms the presence of T. saginata in Ecuador. DNA amplification of some of these taeniids showed different patterns, suggesting the possibility that strain differences exist. These results demonstrate the need for development of useful molecular assays as reliable tools for epidemiological studies on cestodes.

Animals↗

Trichinellosis: old facts and new developments.

Trichinellosis is a helminth zoonosis, which is known since long, but which is emerging or re-emerging in several regions of the world. During the last years the number of cases of trichinellosis in pigs and man in several East-European countries has increased very much due to the breakdown of the veterinary services because of the difficult political and socio-economic situation. In several third world countries on the other hand trichinellosis has become more important due to the increasing number of small traditional pig farms, in which the hygienic conditions are suboptimal. Furthermore, outbreaks of human trichinellosis have been reported due to recently discovered new species such as T. pseudospiralis and T. papuae. Over the last 25 years horsemeat has been more important as a source of human trichinellosis within the European Union than pork or wild boar meat. In Belgium, however, no cases of human trichinellosis have been reported since 1979. A review is presented of the available data on animal trichinellosis in Belgium. The potential risk for the consumer is discussed. Finally, some suggestions are made for a new approach of trichinellosis control in Belgium and the European Union.

Animals↗

Immunisation against East Coast fever by the infection and treatment method: evaluation of the use of ice baths for field delivery and appraisal of an acid formulation of long-acting tetracycline.

Immunisation by the infection and treatment method using the Katete strain is currently the most efficient prophylactic technique to control East Coast fever (ECF) in the endemic areas of the Eastern Province of Zambia. The maintenance of the cold chain in liquid nitrogen up to the time of inoculation and the cost of the reference long-acting oxytetracycline (Terramycin LA, Pfizer) are the main drawbacks of the method. The work presented in this paper aims at reducing the cost of immunisation against ECF by using an ice bath for the field delivery and a cheaper long-acting oxytetracycline formulation as chemotherapeutic agent. In experimental conditions, the results from 40 calves immunised after various periods of storage on ice ranging from 4 to 32 h indicate that deferred immunisation performed with a stabilate kept on ice for up to 6h after thawing has an efficiency of 90%. Moreover, sporozoites kept on ice were still surviving 32 h after thawing. In a field trial, 91 calves were inoculated with a stabilate kept for 3.5-5.5 h after thawing and dilution whereas 86 calves were immunised using the standard method. Clinical and parasitological reactions to immunisation were monitored as well as the seroconversion. In the field trial, the deferred immunisation was more efficient than the standard method. The acid formulation of oxytetracycline that was tested was found as suitable as the reference alkaline formulation for the chemotherapeutic control of the Katete strain in ECF immunisation. One indoor trial was carried out on 10 animals and a field trial involved 93 calves.

Animals↗

Standardised tests in mice and cattle for the detection of drug resistance in tsetse-transmitted trypanosomes of African domestic cattle.

Resistance to the drugs used to control African animal trypanosomosis is increasingly recognised as a constraint to livestock production in sub-Saharan Africa. The most commonly used tests for detection of trypanocidal drug resistance are tests using mice or ruminants, but these suffer from lack of standardisation and hence it may be difficult to compare the results of different investigators. Tests in mice are less expensive than tests in ruminants, but while tests in mice they may be useful as a general guide to resistance in a geographic area they should not be extrapolated to cattle on an individual trypanosome level. Moreover, the commonly used protocols are too laborious for their application to large number of trypanosome isolates on an area-wide basis. This paper presents guidelines for standardised testing of trypanocidal drugs in vivo, and introduces a simplified single-dose test for use in mice, which is convenient for use in areas with limited laboratory facilities. The single-dose test is appropriate for characterisation of geographic areas in terms of trypanocidal drug resistance using large numbers of trypanosome isolates, for making comparisons between areas, and for monitoring changes in trypanocidal drug resistance over time. Multiple-dose tests may be used to determine the degree of resistance of individual stabilates to be determined precisely in mice are also described, but for logistical reasons these will rarely be conducted on more than a few stabilates, and testing of a larger number of stabilates in the single-dose test will generally provide more useful information. Finally, we describe tests in cattle that may be used to determine the efficacy of recommended curative doses of trypanocidal drugs for the treatment of infection with individual trypanosome isolates, including Trypanosoma vivax, which is rarely infective for mice.

Animals↗

Tuning dimensionality by nanowire adsorption on layered materials.

The dimensionality of electronic states determines a number of physical phenomena such as phase transitions, transport, or superconductivity. Employing scanning tunneling microscopy combined with angle-resolved photoemission spectroscopy we demonstrate how the dimensionality of electronic states can be continuously tuned from three to two dimensions. This is achieved by adsorption of nanowires on surfaces of layered crystals without changing the chemical composition of the material. Exemplary results for Rb nanowires on TiTe2 are discussed with the help of electronic structure calculations.

Journal Article↗

Dimeric fragment of the insulin receptor alpha-subunit binds insulin with full holoreceptor affinity.

The insulin receptor (IR) is a dimeric receptor, and its activation is thought to involve cross-linking between monomers initiated by binding of a single insulin molecule to separate epitopes on each monomer. We have previously shown that a minimized insulin receptor consisting of the first three domains of the human IR fused to 16 amino acids from the C-terminal of the alpha-subunit was monomeric and bound insulin with nanomolar affinity (Kristensen, C., Wiberg, F. C., Schäffer, L., and Andersen, A. S. (1998) J. Biol. Chem. 273, 17780-17786). To investigate the insulin binding properties of dimerized alpha-subunits, we have reintroduced the domains containing alpha-alpha disulfide bonds into this minireceptor. When inserting either the first fibronectin type III domain or the full-length sequence of exon 10, the receptor fragments were predominantly secreted as disulfide-linked dimers that both had nanomolar affinity for insulin, similar to the affinity found for the minireceptor. However, when both these domains were included we obtained a soluble dimeric receptor that bound insulin with 1000-fold higher affinity (4-8 pm) similar to what was obtained for the solubilized holoreceptor (14-24 pm). Moreover, dissociation of labeled insulin from this receptor was accelerated in the presence of unlabeled insulin, demonstrating another characteristic feature of the holoreceptor. This is the first direct demonstration showing that the alpha-subunit of IR contains all the epitopes required for binding insulin with full holoreceptor affinity.

Amino Acid Sequence↗

An investigation of clinical correlates of Lewy bodies in autopsy-proven Alzheimer disease.

BACKGROUND: Studies of patients meeting clinical and pathologic criteria for Alzheimer disease (AD) have not consistently found associations between the presence of Lewy bodies (LBs) at postmortem examination and a higher frequency during life of the clinical features of dementia with LBs. OBJECTIVE: To evaluate the clinical correlates of LBs in patients with AD. DESIGN AND METHODS: Fifty-one patients were diagnosed as having probable AD during life and met pathologic criteria for AD. Semiquantitative ratings for LBs were obtained in 4 brain regions: substantia nigra, cingulate, insular cortex, and hippocampus. The patients had been followed up semiannually for up to 9.9 years before death, and clinical features associated with dementia with LBs, including extrapyramidal signs and visual hallucinations, were assessed at each study visit. Logistic regression analyses determined whether patients who had LBs were more likely than those without LBs to express specific clinical signs during follow-up. Cox analyses determined whether patients with LBs developed clinical signs or died earlier. Generalized estimating equations were used to compare rates of cognitive or functional change. RESULTS: Nineteen of the 51 patients had at least 1 LB in one of the studied regions. In no case was a significant relation noted between LBs and the presence of a measured clinical sign. No LB measure was associated with an increased risk of developing any of the evaluated clinical signs earlier in the disease. There was no association between the presence of LBs and more rapid mortality or more rapid disease progression. CONCLUSIONS: In patients diagnosed as having AD during life, we did not observe a relation of LBs noted during postmortem examination with the presence of any clinical feature that we assessed or with the rapidity of disease progression. The relation between LBs and specific clinical manifestations may be tenuous in these patients.

Aged↗

Structural and functional characterization of B-domain deleted recombinant factor VIII.

A new high-purity recombinant factor VIII preparation has been developed for the treatment of hemophilia A. Structurally, this factor VIII preparation, B-domain deleted recombinant factor VIII (BDDrFVIII), differs from other recombinant and plasma-derived factor VIII preparations in that most of the B-domain has been deleted. To ensure that BDDrFVIII contains the requisite structural and functional features, it has been subjected to detailed biochemical and biophysical characterization in comparison to the plasma-derived form of factor VIII. Laboratory studies have shown that the primary, secondary, and tertiary structures of BDDrFVIII and the posttranslational modifications are similar to those of the [80 + 90]-kd form of plasma-derived factor VIII. In addition, BDDrFVIII has full biologic activity compared with full-length factor VIII preparations.

Amino Acid Sequence↗

Six-month comparison of bimatoprost once-daily and twice-daily with timolol twice-daily in patients with elevated intraocular pressure.

The efficacy and safety of bimatoprost, a member of a new class of pharmacological agents called prostamides, were compared with the efficacy and safety of timolol in patients with glaucoma or ocular hypertension. Pooled 6-month results from two ongoing, multicenter, randomized, double-masked, clinical trials were analyzed. Patients were randomized in a 2:2:1 ratio to treatment with bimatoprost 0.03% once a day ([QD] n = 474), bimatoprost 0.03% twice a day ([BID] n = 483), or timolol 0.5% BID (n = 241). Scheduled visits were at prestudy, baseline, week 2, week 6, month 3, and month 6. The primary outcome measure was in diurnal intraocular pressure ([IOP] 8 AM, 10 AM, 4 PM, 8 PM). Bimatoprost QD provided significantly greater mean IOP reductions from baseline than timolol at every time of the day and at each study visit (p </=.05). BID dosing of bimatoprost also provided significantly greater mean IOP reductions than timolol at most timepoints, but was not as effective as QD dosing. The IOP lowering provided by bimatoprost QD was sustained for 6 months. At month 6, the mean IOP reduction from baseline at 10 AM was 8.1 mm Hg (33%) with bimatoprost QD, 6.3 mm Hg (26%) with bimatoprost BID, and 5.6 mm Hg (23%) with timolol. Low target pressures were achieved by a significantly higher percentage of patients in the bimatoprost QD group than in the timolol group. At 10 AM (peak timolol effect) at month 6, IOP </= 17 mm Hg was achieved by 63.9% of bimatoprost QD patients, compared with 37.3% of timolol patients (p <.001). Bimatoprost was safe and well-tolerated, with few discontinuations due to adverse events. The most frequent side effect was trace-to-mild conjunctival hyperemia. Changes in iris pigmentation were reported in 1.1% of bimatoprost patients. There were no other significant findings in slit lamp examinations, ophthalmoscopy, visual acuity, or visual fields, and systemic safety parameters were also unaffected. Together these results indicate that bimatoprost QD is statistically and clinically superior to timolol in lowering IOP, and is safe and well-tolerated in patients with glaucoma or ocular hypertension.

Adrenergic beta-Antagonists↗