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Biomedical subjects

J W Jacobs

Publications and source records attributed to J W Jacobs.

At least 73 records · Page 4Linked to original sources
PubMed1995

Stability of health status measurement in rheumatoid arthritis.

Health status measures in rheumatoid arthritis that have been extensively validated for use in clinical trials are generally used also in correlative studies, e.g. to predict future health status. This application requires stability (repeatability of measurements). The purpose of our study was to determine the stability of commonly used health status measures. Two measurements at an interval of 6 months were then in 99 patients. High stability (alpha = 0.78 to 0.94) was observed for five biomedical measures (grip strength, walking time, platelet count, haemoglobin and erythrocyte sedimentation rate) and five self-report measures (mobility, self care, impact daily activities, anxiety and cheerful mood). Moderate stability (alpha = 0.65 to 0.72) was observed for joint scores, pain, C-reactive protein and depressive mood. The highly stable measures most adequately reflect individual differences, may be applied most reliably in correlative studies and appear to have the largest clinical utility with regard to long-term prediction of health status.

Adult↗
PubMed1995

The prognostic value of the EEG in asphyxiated newborns.

Peripartal asphyxia is still one of the most important factors of neonatal morbidity and mortality and accounts for the majority of non-progressive neurological deficits seen in children. A set of evaluations that may consistently predict outcome in this patient population would be valuable. The purpose of the present retrospective study was to investigate the prognostic value of the early neonatal EEG and Sarnat scoring obtained in 23 asphyxiated term newborns. All infants met strict entrance criteria, regarding asphyxia, and received standard treatment. The relationship between the Sarnat scoring, the early EEG findings, and the clinical follow up examination (at 1,5-7 years) were studied using the Pearson Correlation test and multiple regression. Our study clearly demonstrates a strong correlation between the early neonatal EEG and outcome, even regarding the prediction of minor sequelae (r = 0.79, p < 0.0001). The early neonatal EEG is more accurate in predicting the ultimate clinical outcome than the Sarnat scoring.

Asphyxia Neonatorum↗
PubMed1995

Are tender point scores assessed by manual palpation in fibromyalgia reliable? An investigation into the variance of tender point scores.

To determine the reliability of tender point assessment by manual palpation in patients with fibromyalgia, and to investigate the sources of variance, tender point scores by manual palpation were obtained in 30 fibromyalgia patients by 2 investigators; the assessments were repeated after 1 week. Test-retest stability and inter-observer agreement of tender point scores was moderate to high. The most important sources of variance were inter-individual patient differences in (1) mean tenderness (pain thresholds) and (2) tender point profiles (consistent intra-individual differences between the 14 tender point scores), and (3) residual variance, not attributable to any systematic effect (error). It is concluded that the reliability of tender point assessment by manual palpation is acceptable. It seems to be not less than reliability of assessment by pressure algometer. Tender point scores in fibromyalgia reflect individual differences in mean pain thresholds as well as individual tender point profiles.

Adult↗
PubMed1995

Is it possible to predict the first year extent of pain and disability for patients with rheumatoid arthritis?

OBJECTIVE: To investigate prediction of the extent of suffering during the first year of rheumatoid arthritis (RA) with patient characteristics found to be capable of predicting short term or longterm endpoint disability. METHODS: Ninety-five patients with recently diagnosed RA, participating in a prospective clinical trial, were seen every 3 mo during 1 year. The 12 month and cumulative values of disability (Dutch version of the Health Assessment Questionnaire) and pain (visual analog scale) were related to demographic, clinical, laboratory, and psychological mood variables in correlation and regression analyses. RESULTS: Baseline values of disability and pain were related most strongly to 12 mo and cumulative values of disability; baseline pain was virtually the only important predictor of 12 mo and cumulative pain. Other baseline characteristics had virtually no additional predictive power. CONCLUSION: The short term disease course of RA in terms of disability and pain is most strongly related to the baseline values of these variables, and cannot reliably be predicted with frequently recognized longterm prognostic factors, such as rheumatoid factor status or sex.

Arthritis, Rheumatoid↗
PubMed1994

Combinatorial chemistry--applications of light-directed chemical synthesis.

Combinatorial methods in biology and chemistry are proving to be powerful methods for generating molecular diversity. One approach, light-directed chemical synthesis, combines semiconductor-based photolithography technologies with solid-phase organic chemistry to synthesize large arrays of molecules with potential biological activity. This novel technology has the potential to provide libraries of both natural and synthetic molecules that might be screened rapidly for biological activity.

Amino Acid Sequence↗
PubMed1994

Local muscle hypertrophy due to an arterio-venous malformation.

A 20-yr-old man with progressive, painful diffuse swelling of his right shoulder muscles is reported. The diagnosis was muscle hypertrophy secondary to a congenital arterio-venous malformation (CAVM). Since a CAVM is not infrequently asymptomatic until the age of 20 to 30 yr and develops insidiously, the diagnosis may be delayed. In our patient, MRI rather than ultrasound and CT, led to the final diagnosis.

Adult↗
PubMed1994

Fatal cholestatic hepatitis caused by D-penicillamine.

A 37-yr-old woman with RF-positive RA developed cholestatic hepatitis after 10 days of D-penicillamine therapy. This was discontinued immediately. The cholestasis persisted for the remaining 14 months of her life. Severe hypercholesterolemia developed with xanthelasmata and eventually pancytopenia, which was caused by a massive infiltration of the bone marrow by lipid-containing foam cells. The patient died of sepsis. Review of the literature shows intrahepatic cholestasis to be a rare and idiosyncratic complication of D-penicillamine therapy. To our knowledge, ours is the first documented case of persistent cholestatic icterus.

Adult↗
PubMed1994

Endpoint measures in rheumatoid arthritis clinical trials: group summary and individual patient analysis.

OBJECTIVE: To evaluate the responsiveness of measures of disability, discomfort, and disease process in rheumatoid arthritis (RA) clinical trials, when used as group summary variables and as variables of individual patient improvement. METHODS: Disease outcome and process measures were assessed in 97 patients with RA of recent onset, who were participating in a prospective trial comparing the effectiveness of several drug treatment strategies. Measurements were done after 3 and 6 months of treatment. Group summary analysis was performed with tests of statistical significance of changes, and by calculating effect sizes (i.e., mean change in an endpoint divided by its standard deviation). Individual patient improvement was defined as improvement of > or = 33% compared to baseline, according to recommendations of the recently held Conference on Outcome Measures in Rheumatoid Arthritis Clinical Trials. RESULTS: Almost all mean group changes in endpoints were statistically significant (p < 0.001). Effect sizes and figures on individual patient improvement provided additional information: physical discomfort measures were rapidly responding measures that did not further improve after 3 months; disease process measures, joint count, erythrocyte sedimentation rate and C-reactive protein also responded quickly and kept improving up to 6 months; the disability measures were relatively unchanged at 3 months, and only the self-report questionnaire score showed considerable improvement at 6 months. CONCLUSION: Effect sizes and data on patients who showed clinical improvement in disease process or outcome measures offset the strongly significant p values of statistical tests for almost all endpoint measures. Although discomfort measures rapidly responded to therapy, disability and disease process measures may not reach optimal improvement within 6 months.

Antirheumatic Agents↗
PubMed1994

Interaction of antistasin-related peptides with factor Xa: identification of a core inhibitory sequence.

Antistasin, isolated from the Mexican leech, is a 119 amino acid protein which is a selective and potent inhibitor of coagulation Factor Xa. Previous studies indicated that an arginine residue located at position 34 of the inhibitor was cleaved by Factor Xa during the inhibition reaction. To evaluate this residue as the reactive site of antistasin, and to define shorter fragments of antistasin displaying Factor Xa-inhibitory activity, a series of peptides were synthesized corresponding to amino acids 27-49 of the inhibitor. The most potent peptide synthesized was a disulfide-bridged, 19 amino acid peptide, ATS29-47, which inhibited Factor Xa with a Ki = 35 nM, and increased plasma clotting times by over 4-fold at a concentration of 33 uM. Reduction or sulfation of the cysteine residues in ATS29-47 reduced Factor Xa inhibitory activity by over 95%. Peptides as short as seven residues corresponding to position 33-39 of antistasin displayed Factor Xa inhibitory activity. The peptides did not inhibit thrombin or trypsin at concentrations 1000-fold higher than used in Factor Xa assays. The shortest peptide displaying anticoagulant activity in human plasma was the disulfide-bridged peptide, D-Arg-Cys-Arg-Val-His-Cys-Pro, which increased clotting times by 50% at micromolar concentrations. These results demonstrate that antistasin-related peptide sequences can serve as model structures for the development of novel, low molecular weight anticoagulants.

Amino Acid Sequence↗
PubMed1994

Physical disability and psychological well being in recent onset rheumatoid arthritis.

OBJECTIVE: The association between self-report physical disability scores and psychological well being in patients with rheumatoid arthritis (RA) has been described in several recent publications on patients with widely varying disease durations. We describe the results of a study into these relationships in patients with RA with a disease duration of less than 1 year. METHODS: In this cross sectional study on 113 patients with recent onset RA disability was assessed with 3 self-report indices and with measurement of grip strength. Correlation coefficients between disability measures and disease activity measures (joint tenderness/swelling score, erythrocyte sedimentation rate [ESR)]), psychological well being (cheerful mood, depressive mood, and anxiety), and demographical variables were calculated; hierarchical regression analysis was done with disability measures as the dependent variables. RESULTS: All disability scales were correlated moderately strongly with the joint score and ESR, and with psychological well being. No relation was found with age, sex, marital status, or rheumatoid factor status. Regression analysis showed the variance of 9-15% in disability could be explained by psychological well being after disease activity had been controlled for. CONCLUSION: Patients with recent onset RA appear not to be obviously different with respect to the moderately strong association between physical disability and psychological well being from patients with RA of longer duration in other published reports.

Arthritis, Rheumatoid↗
PubMed1993

An unnatural biopolymer.

A highly efficient method has been developed for the solid-phase synthesis of an "unnatural biopolymer" consisting of chiral aminocarbonate monomers linked via a carbamate backbone. Oligocarbamates were synthesized from N-protected p-nitrophenyl carbonate monomers, substituted with a variety of side chains, with greater than 99 percent overall coupling efficiencies per step. A spatially defined library of oligocarbamates was generated by using photochemical methods and screened for binding affinity to a monoclonal antibody. A number of high-affinity ligands were then synthesized and analyzed in solution with respect to their inhibition concentration values, water/octanol partitioning coefficients, and proteolytic stability. These and other unnatural polymers may provide new frameworks for drug development and for testing theories of protein and peptide folding and structure.

Amino Acid Sequence↗
PubMed1993

Random and site-specific immobilization of catalytic antibodies.

The effects of immobilization on the immunologic and catalytic activity of a catalytic antibody were compared for randomly immobilized (via glutaraldehyde) whole antibody and site-specifically immobilized (via the reactive sulfhydryl group at the base of the fragment) Fab' fragments. Upon immobilization, the specific binding capacity (n) and the catalytic activity decreased significantly for both systems. Increases in the Michaelis constant (KM) were accompanied by corresponding decreases in the equilibrium binding constant determined through immunoassays. For the immobilized Fab', n decreased dramatically with increased protein loading, suggesting that, despite the site-specific attachment and favorable orientation, molecular crowding denatured the Fab' fragments. These results also show that there is an optimal surface coverage, not necessarily at the maximum loading, for both immunologic and catalytic activity. Finally, the combining/active site conformation was probed using electron paramagnetic resonance (EPR) spectroscopy. In all antibody samples, there was no spectral evidence of conformational changes in the antibody active site.

Animals↗
PubMed1993

Measurement of functional ability and health status in the arthritic patient.

Chronic arthritis may have great impact on the patient but also on his or her family, relatives and friends. The assessment of the consequences of chronic arthritis and the effect of therapy not only in terms of physical, but also psychological and social dimensions deserves more attention. Functional ability and health status can be measured using a questionnaire or 'instrument', high-lighting important aspects not quantified with more traditional measurements. In this paper, arguments to apply such instruments more frequently are given. Health status instruments can be used not only to assess beneficial but also deleterious (side-) effects of therapeutic interventions. The properties are summarized of the most frequently used instruments assessing functional ability and health status. Many of these instruments have been evaluated sufficiently for validity and reliability; their sensitivity to detect change seems to be satisfactory. Therefore it is advisable to choose an internationally accepted, frequently used instrument, reflecting the area of interest.

Activities of Daily Living↗
PubMed1993

Corticosteroid pulse therapy in active rheumatoid arthritis.

The infusion of high doses of corticosteroids (corticosteroid pulse therapy, CPT) is used to treat refractory rheumatoid arthritis (RA). In the first part of this article, literature on the efficacy of CPT is reviewed, and different CPT regimens (high-dose, low-dose, oral CPT) are compared. Several CPT regimens are beneficial in RA, the clinical effect lasting 4 to 10 weeks. Only high-dose CPT (1,000 mg methylprednisolone intravenously) has been shown to bridge the gap between the start and the effect (lag time) of a disease-modifying antirheumatic drug initiated at the same time. A retrospective study on the incidence of short-term and long-term side effects of CPT in 50 patients with RA who received a total of 78 pulse regimens is described in the second part. Side effects occurred frequently, but in most cases they were mild. The possible relationship between CPT and osteonecrosis of the femoral head is discussed. It is concluded that CPT is beneficial in RA. A substantial number of patients suffer side effects of varying severity.

Adrenal Cortex Hormones↗
PubMed1993

Transient decrease in osteocalcin and markers of type 1 collagen turnover during high-dose corticosteroid pulse therapy in rheumatoid arthritis.

The effect of corticosteroid pulse therapy on bone metabolism was studied in 10 patients with active RA. We measured alkaline phosphatase, osteocalcin and two recently introduced markers of collagen type 1 metabolism, reflecting synthesis (PICP) and degradation (ICTP). The day after the pulse therapy, there was a statistically significant (P < 0.05) decrease in osteocalcin, PICP and ICTP from the value at start. Three weeks after pulse therapy, these values had returned to baseline. During pulse treatment there is a transient decrease in bone formation, as shown by the changes in osteocalcin and PICP. Because of the changes in ICTP, we conclude that bone resorption is transiently reduced as well, but whether these changes result from a direct or an indirect effect on bone is not clear. ICTP has to be investigated further as a (serum) marker of bone resorption.

Aged↗
PubMed1993

Adjuvant oestrogen therapy does not improve disease activity in postmenopausal patients with rheumatoid arthritis.

OBJECTIVE: To investigate whether oestrogens can be used as treatment to diminish disease activity in women with rheumatoid arthritis. METHODS: Forty postmenopausal female patients with active rheumatoid arthritis participated in a placebo-controlled, double-blind study on the possible beneficial effect of adjuvant treatment of oestradiol on disease activity. RESULTS: Thirty three patients completed 52 weeks of treatment with 2 mg oestradiol-valerate or placebo. No statistically significant difference was found in and between both treatment groups with regard to articular indices, pain score by visual analogue scale, erythrocyte sedimentation rate and health questionnaire on daily activities before, during and at the end of the study. CONCLUSION: This first randomised prospective placebo-controlled study shows no beneficial effect of oestrogens on disease activity in postmenopausal female patients with rheumatoid arthritis.

Aged↗