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Biomedical subjects

J Killestein

Publications and source records attributed to J Killestein.

26 records · Page 2Linked to original sources

MS functional composite: relation to disease phenotype and disability strata.

OBJECTIVE: The MS Functional Composite (MSFC), a recently developed outcome measure for clinical trials, was applied to 240 patients with MS to explore its utility in different subgroups of MS and for comparison with the Expanded Disability Status Scale (EDSS). METHOD: Three clinical dimensions were examined: arm/hand function, leg function/ambulation, and cognition. Predictions of relative scores on the MSFC and its components in three major MS phenotypes (relapsing-remitting, primary progressive, and secondary progressive) and three strata of disability were developed and tested. Also, correlations with EDSS were calculated and the effect of an external reference population was assessed. RESULTS: Mean MSFC score was positive in the relapsing-remitting (0.4) and mildly disabled (0.4) groups and negative in the secondary progressive (-0.3), primary progressive (-0.4), and moderately (-0.07) and severely disabled (-1.0) groups. The correlation between EDSS and MSFC was strong (-0.68). EDSS correlated strongly with ambulation in secondary and primary progressive patients and severely disabled patients, moderately with arm/hand function for all analyzed groups, and not at all with cognition. Comparison with an external reference population showed changes in MSFC- and Z-scores, but did not result in altered differences between the subgroups. CONCLUSION: Our prospective study in subgroups of MS confirmed and extended the construct validity of the MSFC. The MSFC also showed good concurrent validity with the EDSS, and includes information about cognition.

Adolescent↗

Contrasting responses to interferon beta-1b treatment in relapsing-remitting multiple sclerosis: does baseline interleukin-12p35 messenger RNA predict the efficacy of treatment?

Interferon (IFN)-beta treatment is effective in relapsing-remitting multiple sclerosis (RR-MS) via an as yet unidentified mechanism. In the present study, we investigated whether the expression of messenger RNA (mRNA) encoding the interleukin (IL)-12 subunits p40 and p35, IL-12 receptor chains, IL-18, tumor necrosis factor-alpha (TNFalpha), IFNgamma, IL-10, IL-4, or transforming growth factor-beta in unstimulated whole blood of 26 RR-MS patients changed during 6 months of IFNbeta-1b treatment. In these patients, a significant change was found in TNFalpha mRNA, whereas changes in IL-12 receptor-beta2 and IL-10 mRNA showed a trend. IFNbeta-1b-related changes in cytokine mRNA expression were next evaluated in clinical subgroups of RR-MS patients classified as either clinical responders or nonresponders on the basis of Expanded Disability Status Scale progression and the number of relapses and steroid interventions needed in the 2 years before initiation of treatment compared with the 2 years after initiation of treatment. These subgroups showed different response patterns to IFNbeta-1b treatment with respect to IL-10, TNFalpha, and IL-18 only. Surprisingly, clinical responders displayed no change in these cytokines, whereas nonresponders showed a decrease in TNFalpha and IL-18 mRNA as well as a transient increase in IL-10 mRNA. Baseline levels of IL-12p35 mRNA were lower in the responders compared with the nonresponders: this marker correctly predicted the clinical outcome in 81% of the 26 patients under investigation.

Adult↗

Quality of life during the first 6 months of interferon-beta treatment in patients with MS.

OBJECTIVES: To determine the quality of life (QoL) of MS patients during the initial 6 months of treatment with interferon-beta (IFN-beta). Furthermore, to determine whether changes in QoL relate to disability, emotional state, therapeutic expectations or side effect profile. BACKGROUND: IFN-beta has been shown to have beneficial effects on the course of MS. Since the aim of IFN-beta treatment is not to cure but to slow down the disease it is important to know how this treatment affects QoL. Surprisingly, the impact of treatment with IFN-beta on QoL measures has not been extensively studied so far. METHODS: Case report documentation, including EDSS, SF-36 and MADRAS scores, of 51 relapsing-remitting MS patients treated with IFN-beta was obtained at baseline and at months 1, 3 and 6. Patients also filled in a form about their expectations of therapy and a questionnaire on side effects. RESULTS: During treatment there was a significant linear trend indicating improvement in the role-physical functioning (RPF) scale of the SF-36 (F(1,50)=4.9, P=0.032). A transient decrease at month 1 was found in the scale for bodily pain, indicating more experienced pain (F(1,50)=19.8, P<0.001). Subgroup analysis showed that patients with most depressive symptoms on the MADRAS at baseline contributed most to the increase in RPF scores over time (F(1,24)=5,6 P=0.026). Furthermore, we found associations between adverse event scores and several domains of QoL. CONCLUSIONS: Our findings suggest that IFN-beta therapy has an impact on QoL of MS patients in that it improves role-physical functioning and transiently worsens experienced bodily pain. QoL during treatment with IFN-beta is influenced by depressive symptoms at baseline as well as by treatment-associated side-effects. Multiple Sclerosis (2000) 6 338 - 342

Adjuvants, Immunologic↗

[Therapeutic applications and biomedical effects of cannabinoids; pharmacological starting points].

A broad range of therapeutic applications has been suggested for cannabis or its pharmacologically active compound (tetrahydrocannabinol; THC) in many publications. Psychotropic side effects and the anecdotal character of the research have limited the pharmacotherapeutic use of THC until now. Therefore, the Netherlands Health Council recently decided negatively on this matter. Besides several cannabinoid receptor subtypes present in the central nervous system and peripheral tissues endogenous cannabinoids have been detected. These endogenous cannabinoids appear to play an important role in signal transduction, which may be starting points for therapy regarding: cardiovascular diseases, multiple sclerosis and spinal cord disorders. cerebrovascular accident and brain trauma, neurodegenerative diseases, epilepsy, pain management, glaucoma, oncologic and aids-related disorders such as nausea, vomiting and appetite problems.

Acquired Immunodeficiency Syndrome↗

Outcome of cataract surgery by a general medical doctor at district level, Zimbabwe: a retrospective follow-up study.

From January 1990 until October 1992, 103 Zimbabwean patients underwent intracapsular cataract extraction by a general medical doctor. Of the first 100 patients operated upon, 50 were traced of which 37 could be assessed adequately. Operative complications and visual acuities after three months show that this is an effective means of restoring sight, but that a longer period of training of a general medical doctor than one month is adviseable. Twenty-five patients (68%) have a vision of 3/60 or better, which would have been 34 patients (92%) if post-operative refraction and adequate provision of glasses had been provided. The careful attention required regarding patients' needs and refraction is stressed by the authors. The study or better this factual report suggests that cataract surgery performed by a general medical doctor is an alternative for clearing the cataract backlog in developing countries.

Aged↗