Biomedical subjects

J Brandt

Publications and source records attributed to J Brandt.

At least 55 records · Page 3Linked to original sources

PubMed2004

Two year maintenance of efficacy and safety of infliximab in the treatment of ankylosing spondylitis.

OBJECTIVE: To obtain results of the second year extension of an original 3 month randomised, placebo controlled trial (and the 1 year extension study) assessing the use of infliximab, a monoclonal antibody to tumour necrosis factor alpha, for the treatment of patients with ankylosing spondylitis (AS). METHODS: Of the 54 patients with AS who completed the first year of the study, 52 continued to receive infliximab 5 mg/kg every 6 weeks up to week 102. The primary end point was the proportion of patients achieving at least 50% improvement from baseline in the Bath AS Disease Activity Index (BASDAI) at week 102. Other assessments included patient and physician global assessments, quality of life as assessed by Short Form-36, Bath AS Functional Index, Bath AS Metrology Index, and C reactive protein (CRP). RESULTS: Improvement in signs and symptoms of AS seen during the first year of the study was sustained during the second year. Forty nine patients (71% of 69 enrolled patients and 49/52 (94%) patients who started year 2) completed the study up to week 102. Thirty (58%) patients achieved at least 50% improvement from baseline in the BASDAI score at week 102. Scores for other efficacy assessments were similar at weeks 54 and 102. Median CRP levels remained low at weeks 54 and 102 (3.9 and 4.3 mg/l, respectively). Side effects during the second year of the study were similar to those of the first year of treatment with infliximab. CONCLUSIONS: Patients with AS treated for 2 years with infliximab 5 mg/kg exhibited a good and durable clinical response.

Adult↗

PubMed2004

Dementia in hippocampal sclerosis resembles frontotemporal dementia more than Alzheimer disease.

OBJECTIVE: To characterize the clinical course of pathologically diagnosed hippocampal sclerosis dementia (HSD). BACKGROUND: Dementia associated with HSD is incompletely characterized. Previous studies suggest similarities to both Alzheimer disease (AD) and frontotemporal dementia (FTD). METHODS: Case-control analysis of the clinical course of patients with HSD, FTD, and AD from a neuropathology autopsy series conducted by a university hospital. Case histories were reviewed. Cumulative prevalence of behavioral, cognitive, psychiatric, and language symptoms were compared between groups, as was time of symptom onset. Clinical diagnostic criteria for FTD and AD were applied to case histories. Sensitivity and specificity of clinical FTD diagnostic criteria (Report of the Work Group on FTD and Pick's disease) were computed. RESULTS: Cumulative prevalence of symptoms in HSD was most similar to that of FTD and differed from AD. Behavioral abnormalities such as decreased grooming and inappropriate behavior were more prevalent in HSD and FTD than AD. Hyperorality, inappropriate behavior, and decreased interest had earlier onset in HSD and FTD. Cognitive symptoms of disorientation, dyscalculia, apraxia, and agnosia were more prevalent in AD, as were psychiatric symptoms of hallucinations, delusions, and aggression. Most HSD patients met diagnostic criteria for FTD. Criteria sensitivity was 64.0% and specificity was 73.7%. CONCLUSIONS: FTD is a clinical syndrome associated with heterogeneous neuropathology. The clinical course of HSD is more similar to that of FTD than AD. These findings, together with the neuropathologic data presented in the accompanying article, support expanding the scope of FTD (Pick complex) to include HSD.

Afferent Pathways↗

PubMed2004

Onset and rate of striatal atrophy in preclinical Huntington disease.

BACKGROUND: Huntington disease (HD) is characterized by striatal atrophy that begins long before the onset of motor symptoms. OBJECTIVE: To determine when striatal atrophy begins, the extent and rate of atrophy before diagnosis of motor symptoms, and whether striatal atrophy can predict when symptom onset will occur. METHODS: Caudate and putamen volumes were measured on MRI scans of 19 preclinical subjects with the HD gene expansion who were very far (9 to 20 years) from estimated onset, and on serial scans from 17 preclinical subjects, six of whom were diagnosed with HD within 5 years after the initial scan. RESULTS: Striatal volumes were significantly smaller for the subjects who were very far from estimated onset than for age-matched control subjects. Statistical models fit to the longitudinal data suggest that rate of caudate atrophy becomes significant when subjects are approximately 11 years from estimated onset and rate of putamen atrophy becomes significant approximately 9 years prior to onset. In the six incident cases, caudate and putamen were approximately one-third to one-half of normal volume at diagnosis, and caudate volume alone was able to predict with 100% accuracy those subjects who would be diagnosed within 2 years of imaging. CONCLUSIONS: Striatal atrophy begins many years prior to diagnosable HD, and assessment of atrophy on MRI may be very useful in both predicting HD onset and in tracking progression in future therapeutic trials in preclinical subjects.

Adult↗

PubMed2004

Recirculation of Trypanosoma brucei brucei in cattle after T. congolense challenge by tsetse flies.

The effect of challenging cattle, chronically infected with Trypanosoma brucei brucei, with T. congolense on the development of the T. b. brucei infection was investigated. For this purpose, nine experimental animals were first infected with T. b. brucei through the bites of infected tsetse flies. Once the T. b. brucei had developed into a chronic infection, that was difficult to detect using routine parasitological diagnostic tools, seven of the experimental animals were challenged by tsetse flies infected with T. congolense. Two of the animals infected with T. b. brucei were kept as control. The infection with T. congolense resulted in a sudden increase in the parasitaemia of T. b. brucei. In the T. b. brucei control animals, on the other hand, the parasitaemia remained below the level of detection. The epidemiological repercussions of this increase in the parasitaemia of T. b. brucei after infection with T. congolense are discussed.

Animals↗

PubMed2004

Analysing chronic spinal changes in ankylosing spondylitis: a systematic comparison of conventional x rays with magnetic resonance imaging using established and new scoring systems.

OBJECTIVES: To compare conventional radiography and magnetic resonance imaging (MRI) for detection of chronic changes in the spine of patients with ankylosing spondylitis (AS). METHODS: Assessment of chronic lesions in conventional x rays and T1 weighted MRI turbo spin echo sequences was performed with the established x ray scores BASRI and SASSS, the new Berlin score, and the MRI scoring system ASspiMRI-c All images were read twice and "blindly" by two readers. One vertebral unit (VU) was defined as the region between two virtual lines drawn through the middle of each vertebra. Definite involvement was defined as a score > or =2 in a spinal segment. RESULTS: Thirty nine patients with AS were examined (25 (64%) male, mean age 40.9 years, 33/36 (92%) HLA-B27 positive). The Berlin score correlated with the BASRI (r = 0.73, p = 0.01). The ASspiMRI-c correlated well with the BASRI and the Berlin score (r = 0.66 and r = 0.51, respectively, p = 0.01). The Berlin x ray score showed that 12/35 (34.3%), 13/35 (37.1%), and 12/28 (31.6%) patients had definite involvement of the cervical spine (CS), thoracic spine (TS), and lumbar spine (LS), respectively. The ASspiMRI-c showed that 10/36 (27.8%), 21/36 (58.3%), and 9/35 (25.7%) patients had definite involvement of the CS, TS, and LS, respectively. Syndesmophytes were found in 14.4% of all VUs with 90% agreement between the SASSS and Berlin score. CONCLUSIONS: T1 weighted MRI can detect chronic lesions in AS. The two new scoring systems proved valid in comparison with established scoring systems and based on aspects of the OMERACT filter. The thoracic spine is most commonly affected in AS. This part of the spine is best assessed by MRI.

Adult↗

PubMed2004

Development and preselection of criteria for short term improvement after anti-TNF alpha treatment in ankylosing spondylitis.

OBJECTIVE: To develop and compare candidate improvement criteria for anti-TNFalpha treatment in ankylosing spondylitis with optimal discriminating capacity between treatment and placebo. METHODS: Data from two randomised controlled trials which included 99 patients treated with infliximab or etanercept were used to evaluate 50 candidate improvement criteria. These were developed on the basis of pain, patient's global assessment, function, morning stiffness, spinal mobility, and C reactive protein. Different levels of improvement in each domain (20-60%) were used to define Boolean type criteria. These criteria were compared with different percentages of improvement on the BASDAI and with modified ASAS improvement criteria. Bootstrap methods were applied to calculate 95% confidence intervals (CI) of the chi(2) test values to select the best candidate improvement criteria. RESULTS: The best performing improvement criteria were "20% improvement in five of six domains" (chi(2) = 31.9 (95% CI, 18.0 to 46.9)) with a low placebo response of 2.9% and a high response to infliximab of 67.7%; and "ASAS 40% improvement" (chi(2) = 26.5 (13.3 to 41.1)), with response to placebo of 5.7% and response to infliximab of 64.7%. The good discriminating capacity of the two improvement criteria was confirmed by the combined dataset of the infliximab and etanercept trial. CONCLUSIONS: The "five of six" improvement criterion has the advantage of including the objective domains spinal mobility and acute phase reactants, but requires only 20% improvement. The ASAS 40% improvement criterion has the advantage of setting a high threshold, but only in patient reported outcomes. The choice between these improvement criteria needs to be based on further validation from upcoming trials.

Adult↗

PubMed2004

Prediction of a major clinical response (BASDAI 50) to tumour necrosis factor alpha blockers in ankylosing spondylitis.

BACKGROUND: TNFalpha blockers have been shown to be highly efficacious in patients with active ankylosing spondylitis (AS). OBJECTIVE: To identify parameters predicting the clinical response to TNF blockers in AS. METHODS: Patients with active AS participated in two placebo controlled, randomised trials conducted in Germany with infliximab (n = 69) and etanercept (n = 30), respectively. For inclusion in either trial patients had to have high disease activity (BASDAI >or=4) and a spinal pain score (numerical rating scale 0-10) >or=4 despite treatment with NSAIDs. A major clinical response was defined as a 50% improvement of the initial BASDAI (BASDAI 50) after 12 weeks' treatment with active drug. Logistic regression likelihood ratio tests (univariate and multivariate), Student's t test, and chi(2) tests were performed. RESULTS: Univariate analysis showed the following to be predictors of a major response (BASDAI 50) to treatment: shorter disease duration (p = 0.003); lower BASFI (p = 0.007); younger age (p = 0.009); raised ESR (p = 0.033); raised CRP (p = 0.035). After adjustment for disease duration, BASFI, ESR, and CRP, but not age, remained significantly associated. After adjustment for disease duration and for BASFI, ESR, CRP, and in addition, a higher BASDAI were significantly associated with response. The best multivariate model built by stepwise regression contained the covariables disease duration, BASFI, BASDAI, and CRP. CONCLUSION: A shorter disease duration, younger age, and a lower BASFI are predictors of a major clinical response to TNF blockers in active AS. Raised CRP and a higher BASDAI may also be valuable predictors. These data need to be confirmed in further studies.

Adult↗

PubMed2004

Trypanocidal drug resistance in eastern province of Zambia.

A survey to investigate resistance to drugs used in the treatment of bovine trypanosomosis was conducted in the eastern province of Zambia between 1996 and 1998. A cross-sectional study was conducted in three districts (Petauke, Katete, Lundazi) at 34 village sampling sites selected at random from villages that had shown greater than 6% prevalence of bovine trypanosomosis during an earlier survey. A longitudinal study was conducted in same three districts over a 1-year period. The study sites were chosen from the cross-sectional study and included eight sites showing high trypanosomosis prevalence and where no control activities were recorded. Use was made of parasitological methods, tests of resistance in cattle and mice and isometamidium-ELISA. Overall mean prevalence of trypanosomosis was 14.4, with 96% of infections caused by Trypanosoma congolense. The remainder was caused by Trypanosoma vivax (2%) and Trypanosoma brucei (2%). Tests in mice showed that of the stabilates collected, 24 (34%) were resistant to only isometamidium chloride, 8 (11.3%) were resistant to only diminazene aceturate, 1 (1.4%) was resistant to both drugs, and 38 (53.5%) were sensitive to both drugs. At least 2 out of 27 stabilates tested in cattle appeared to be resistant to trypanocidal drugs, 1 to isometamidium and 1 to diminazene. Isometamidium could be detected in only 63 (4.1%) of 1526 serum samples from cattle in the study. Only 6 (2.8%) of 212 serum samples from trypanosome-infected cattle had serum levels of the drug above 0.4 ng isometamidium per ml serum which is indicative for drug resistance in the infecting parasite population. Although some drug resistance is apparent, diminazene aceturate and isometamidium chloride can still be expected to be effective as a sanative pair in this area in most cases, since not more than 1 stabilate of 71 investigated showed evidence of resistance to both drugs.

Animals↗

PubMed2004

The transmission of mixed Trypanosoma brucei brucei/T. congolense infections by tsetse (Glossina morsitans morsitans).

Laboratory experiments and field observations clearly show that tsetse flies can be carriers of mixed trypanosome infections. Question remains how easy it is for the tsetse fly to acquire such a mixed infection during the first bloodmeal. This is of particular importance in the epidemiology of Trypanosoma brucei s.l., often a cryptic infection and difficult to transmit to non-teneral tsetse flies. To determine the transmission rate of T. brucei as part of a mixed infection, teneral Glossina morsitans morsitans were fed once on cattle with a mixed (Trypanosoma brucei brucei/Trypanosoma congolense) or single (T. brucei) infection. Of the 140 flies fed on animals with a mixed infection and examined 30 days later, 4 had a metacylic T. brucei infection, 29 a T. congolense infection and 13 a mixed T. brucei/T. congolense infection. There was no significant difference between the transmission rate of T. brucei as a single or as part of a mixed infection. The high proportion of mixed T.b. brucei/T. congolense infections was explained best by a model implying that if a fly is refractory to T. congolense, it is also refractory to T.b. brucei and vice versa. Hence, results suggest that the transmission of T.b. brucei is affected mainly by the vectorial capacity of flies and not by concurrent trypanosome infections in the host.

Animals↗

PubMed2004

[Measurement of quality of life in patients with active ankylosing spondylitis being treated with infliximab-a comparison of SF-36 and SF-12].

BACKGROUND: Quality of life as a part of the WHO definition of health is an important assessment tool for measuring the success in the treatment of chronic diseases. The short form 36 questionnaire (SF-36), which is measuring health related quality of life, was used in a multicentre placebo controlled study in patients with ankylosing spondylitis (AS) treated with the anti-TNF-alpha antibody infliximab. As previously reported, substantial changes of almost all outcome parameters were observed in this study because of the substantial clinical improvement that is known to occur in most patients treated with anti-TNF agents. The short form 12 questionnaire (SF-12) is shorter and quicker to complete as the SF-36. The summary scales of both questionnaires were compared in this study to answer the question whether the SF-12 can also be used in AS patient populations without too much loss of information. Using the shorter from could be an advantage for further studies in patients with AS, for example, the inception cohort for spondyloarthritides within the German Network of competence in rheumatology. Furthermore the data can be compared to the German standard population. METHODS: In this multicentre placebo controlled study 70 patients with active disease were enrolled: 35 AS patients received placebo, 35 were treated with infliximab, 5 mg/kg at week 0/2/6. Thereafter all patients were treated in an open study with infliximab at 5 mg/kg every 6 weeks. The disease activity (BASDAI), function (BASFI), mobility (BASMI), pain (NRS) and CRP as well as SF-36 were assessed. Data to calculate the SF-12 were extracted from the SF-36 questions and compared concerning agreement of individual levels, correlation with each other and with the BASFI, sensitivity to change and missing values. RESULTS: All outcome parameters for disease activity as well as all subscales of health related quality of life improved in patients with active AS treated with infliximab. The comparability of the sum components for SF-12 and SF-36 were high (physical health r=0.912 and mental health r=0.957). CONCLUSION: These data suggest that the shorter version of the SF-36, the SF-12, is capable to measure quality of life in clinical studies with AS patients.

Activities of Daily Living↗

PubMed2004

[Current therapy with TNFalpha blocking agents for ankylosing spondylitis and undifferentiated spondyloarthritis].

The Spondyloarthritides (SpA) comprise a group of inflammatory rheumatic diseases which mostly affect the spine and the larger peripheral joints. The most common entities in this group are ankylosing spondylitis (AS) and undifferentiated spondyloarthritis (uSpA). Treatments with disease-modifying or remission-inducing properties for patients with AS are so far not available. However, in the light of relevant individual and socioeconomic consequences this is an unmet medical need. Recently, etanercept in addition to infliximab has shown substantial efficacy which might even be disease controlling. For both TNFalpha blocking agents, large randomized placebo-controlled trials have proven their efficacy with an acceptable profile of adverse events. In open trials these drugs also work in patients with uSpA. There is some hope now that the TNFalpha blocking agents could stop the development of AS in patients starting with uSpA.

Antibodies, Monoclonal↗

PubMed2004

A Bayesian approach for estimating values for prevalence and diagnostic test characteristics of porcine cysticercosis.

Several diagnostic techniques are used to estimate the prevalence of the zoonotic tapeworm Taenia solium in pigs, but none of these tests are perfect, making interpretation of results difficult. A Bayesian approach was used to estimate values for the prevalence and diagnostic test characteristic of porcine cysticercosis by combining results of four imperfect tests. Village pigs (N = 868) slaughtered in Lusaka (Zambia), were bled, and tongue and routine meat inspected; and serum antibody and parasite antigen concentrations were determined by ELISA. A model, based on a multinomial distribution and including all possible interactions between the individual tests required 31 parameters to be estimated, but actually allowed only 15 parameters (i.e. had 15 degrees of freedom) to be estimated. Therefore, prior expert opinion on specificity and (in)-dependence of the tests was entered in the model, resulting in a reduction of the number of parameters to be estimated. The estimated prevalence of porcine cysticercosis was 0.642 (95% confidence interval 0.54-0.91). The performances of the tests were (sensitivity (se)-specificity (sp)): tongue inspection (se 0.210-sp 1.000), meat inspection (se 0.221-sp 1.000), Ab-ELISA (se 0.358-sp 0.917), Ag-ELISA (se 0.867-sp 0.947). To validate the estimates obtained from the model we performed a second study: 65 randomly purchased Zambian village pigs were bled for serum antibody and antigen determination, their tongue and meat inspected; and in addition, the carcasses were dissected for total cysticercus counts (gold standard). Cysticerci were found in 31 pigs (prevalence 0.477, 95% confidence interval 0.35-0.60), overlapping with the estimated prevalence in the first study. Sensitivity and specificity values obtained for the aforementioned tests in this study were in agreement with those estimated. A Bayesian analysis framework offers the possibility to combine prior opinion with experimental data to more accurately estimate the real prevalence of porcine cysticercosis in the absence of a gold standard.

Animals↗

PubMed2004

In vitro titration of Theileria parva tick derived stabilates.

Immunization against the protozoan Theileria parva by infection and treatment has proved to be very efficient for the control of East Coast fever, an acute and often-fatal lymphoproliferative tick-borne disease of cattle in Eastern, Central and Southern Africa. The immunizing dose of live T. parva sporozoites used in this method is usually determined by in vivo titration. An alternative in vitro method of quantification of sporozoites in whole tick-derived stabilates is proposed. The method consists of incubating serially diluted T. parva stabilates with bovine peripheral blood lymphocytes, the host cell that is infected naturally. Allowing the cultures to incubate undisturbed for the full cultivation period (10 days) reduced the variability among replicate titrations. Fungal contaminations were avoided by centrifuging stabilates at 400 g prior to the incubation, which did not precipitate sporozoites significantly. Fungistatics, Nystatin and Flucytosine, did not appear to interfere with the in vitro development of T. parva but their effect on fungal growth was limited. In vitro titration data were compared to in vivo infection data for 2 stabilates. In vitro titration of T. parva sporozoites should allow more ethical and efficient research on the preparation and storage of T. parva tick-derived stabilates.

Animals↗

PubMed2004

[Gallstone ileus].

Explore the source record for details and available documents.

Cholecystectomy↗

PubMed2004

Impact of anti-tumour necrosis factor alpha treatment on admissions to hospital and days of sick leave in patients with ankylosing spondylitis.

OBJECTIVE: To analyse the impact of infliximab treatment on the number of hospital inpatient days and days of sick leave in patients with active ankylosing spondylitis (AS). METHODS: The data of a 2 year open extension study of a 12 week, double blind, randomised, placebo controlled trial, in which all patients with AS were treated with 5 mg/kg infliximab, were used to investigate the effect of anti-TNF treatment on admissions to hospital and days of sick leave. All patients were interviewed at baseline and at regular intervals during the study to collect this information by questionnaires. Patients who completed 2 years of treatment (n = 49) and those who did not (n = 20) were analysed separately. Sick leave analysis was restricted to currently employed patients (n = 38). RESULTS: During the 12 months before the screening visit, 20/49 (41%) completers had been admitted to hospital. After 1 and 2 years of treatment this percentage was reduced to 5/49 (10%; p<0.01), corresponding to a significant decrease in the mean number of inpatient days: from 11.1 to 0.6 after 1 year (p<0.01) and 2.9 after 2 years (p<0.01), respectively. No changes were seen in the dropout group. CONCLUSION: The use of infliximab in patients with active AS reduces some important costs of AS, but additional studies with detailed cost calculations are needed.

Adult↗

PubMed2004

[In vitro long-term culture of human bone under physiological load conditions].

There is evidence that mechanical loading is an important, if not the most important factor influencing bone mass and architecture. Investigations under in vivo conditions and cell culture methods, performed during the last years, helped to elucidate these mechanisms. However, the mechanisms by which load bearing acts on bone tissue are until now not completely understood. It is well accepted that weight-bearing exercise increases bone mass and on the other hand lower physical activity engenders bone loss. But neither a physiological threshold for bone loss or bone growth nor the character of the mechanical stimulus concerning amount, frequency and duration of the applied load are known. Even more speculative is the idea how this signal is transformed into the biological response of growing bone. Three-dimensional bone-culture-systems with simultaneous applied mechanical load enables to improve the knowledge of regulation of bone metabolism. We show the results of a long-term in vitro experiment with human cancellous bone under physiological load conditions.

Adaptation, Physiological↗

PubMed2003

Lyophilisation and resuscitation of sporozoites of Theileria parva: preliminary experiments.

Lyophilisation of Theileria parva sporozoite stabilates used for immunisation of cattle against East Coast fever would greatly improve vaccine storage and delivery. We report three attempts to lyophilise and resuscitate the sporozoites of T. parva. Sporozoites survived lyophilisation and were effective for immunisation. Lyophilised stabilate survived for 2 weeks at 5 degrees C and for 12 weeks at -20 degrees C. Although the viability of the stabilates was severely reduced during lyophilisation, this work suggests that this method has potential and should be considered for other Apicomplexan parasites such as Babesia sp. or Plasmodium sp.

Animals↗

PubMed2003

Taeniosis-cysticercosis in man and animals in the Sierra of Northern Ecuador.

Taenia solium is endemic in the Andean region of Ecuador. The recent rediscovery of Taenia saginata in humans urges to reconsider some assumptions in relation to the epidemiology of the taeniosis/cysticercosis complex in this country.Therefore, data were compiled on the infection of both tapeworms in man and animals in Pichincha and Imbabura provinces in the Andean region, north of Quito. On post mortem inspection 3 out of 806 (0.37%) carcasses had T. saginata metacestodes, however, 35 sera out of 869 (4.03%) showed circulating antigen in a monoclonal antibody-based sandwich ELISA (Ag-ELISA). Porcine cysticercosis was detected in 15 out of 2896 (0.52%) carcasses and 93 out of 1032 serum samples (9.01%) were positive in Ag-ELISA. In humans, 4.99% (215 out of 4306) cases of antigen positives were found, whereas coprological examination of 1935 stools resulted in 30 positive cases (1.55%). The limited number of adult tapeworms (29) that were collected does not allow firm conclusions on the proportion of each species, but in total 21 specimen were identified as T. saginata and 8 as T. solium. These data have been discussed in view of the epidemiology of human cysticercosis.

Animals↗