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Biomedical subjects

Dirk Dressler

Publications and source records attributed to Dirk Dressler.

27 records · Page 2Linked to original sources
PubMed2003

Botulinum toxin type B in antibody-induced botulinum toxin type A therapy failure.

Recently, it was reported that botulinum toxin type B complex (BoNT/B) (NeuroBloc(R), Elan Pharmaceuticals) can produce an adequate therapeutic response in patients with antibody induced failure of botulinum toxin type A complex (BoNT/A) therapy. We wanted to study whether this effect is transient or sustained. For this, 10 consecutive patients (6 males, 4 females, age 54.6 +/- 14.3 years, duration of illness 15.8 +/- 7.0 years) with complete BoNT/A therapy failure and BoNT/A antibody titres in excess of 10mU/ml in the mouse diaphragm assay (MDA) received BoNT/B in an initial dose of 12370 +/- 1804MU. After the first BoNT/B application the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) improved from 20.1 +/- 3.0 to 11.9 +/- 3.4. In all patients systemic anticholinergic side effects occurred. Three patients had stable continuous responses to two, three and five subsequent BoNT/B applications. Six patients showed complete secondary therapy failure to the second or third subsequent BoNT/B applications. Side effects did no longer occur. In four of them the BoNT/B doses were doubled without producing any therapeutic benefit or any side effects. In five of them MDA testing was performed and revealed BoNT/B antibody titres in excess of 1mU/ml. One patient lost half of her initial BoNT/B responsiveness indicating partial secondary BoNT/B therapy failure. This partial therapy failure was seen on two consecutive application series and has not proceeded to complete therapy failure so far. BoNT/B seems to be only temporarily effective in the majority of patients with BoNT/A antibody induced therapy failure. Whether the formation of BoNT/B antibody points to a high antigenic potency of BoNT/B, to an increased immunoreactivity in BoNT/A antibody carriers or whether it is due to the large amount of protein applied in BoNT/B therapy needs to be studied.

Adult↗
PubMed2003

Autonomic side effects of botulinum toxin type B treatment of cervical dystonia and hyperhidrosis.

Recently, botulinum toxin type B (BT-B) has become available to treat muscle hyperactivity in cervical dystonia (CD). When we started the clinical use of BT-B, we noticed a side effect profile not seen with botulinum toxin type A (BT-A) before. Altogether 30 consecutive patients were included in this open controlled study. 24 patients were treated for CD with 11,310 +/- 2,616 mouse units (MU) of BT-B (NeuroBloc) and 6 for focal hyperhidrosis (HH) with 4,000-10,000 MU. In 5 of them, BT-A (Botox) was used additionally for comparison of effectiveness. In CD, side effects consisted of dryness of mouth (total 21, duration 4.4 +/- 2.0 weeks, 10 severe, 7 moderate, 4 mild), accommodation difficulties (7), conjunctival irritation (5), reduced sweating (4), swallowing difficulties (3), heartburn (3), constipation (3), bladder voiding difficulties (2), head instability (1), dryness of nasal mucosa (1) and thrush (1). In HH, side effects consisted of accommodation difficulties (4), dryness of mouth (2) and conjunctival irritation (1). Autonomic side effects occur far more often after BT-B than after BT-A. Their localization suggests systemic BT-B spread. BT-B should be applied carefully in patients with pre-existent autonomic dysfunction, additional anticholinergic treatment and in conditions where anticholinergics are contraindicated.

Adult↗
PubMed2002

Botulinum toxin antibody type A titres after cessation of botulinum toxin therapy.

In some patients, therapy with botulinum toxin type A (BT-A) becomes ineffective due to formation of antibodies (BT-A-AB). The time course of BT-A-AB titres after cessation of BT-A therapy was quantitatively studied to determine whether and when they might drop. Thirteen patients (eight women, five men) with various dystonic syndromes and complete secondary therapy failure (CSTF) were included in this study (age at initiation of BT-A therapy, 48.2 +/- 11.3 years; number of injection series, 7.7 +/- 2.9; treatment time, 678.8 +/- 385.6 days; mean interinjection interval, 90.4 +/- 35.5 days; mean single dose, 546.7 +/- 336.9 EMU; cumulative dose, 4185.1 +/- 3375.7 EMU [1 EMU = 1 botox MU = 3 dysport MU]). During a monitoring period of at least 750 days after occurrence of CSTF, two or more BT-A-AB tests using the quantitative mouse diaphragm assay were performed. Eight of 13 BT-A-AB titres decreased. The onset of decrease could be detected after between approximately 500 and 1,750 days. After 1,250 to 2,250 days they had dropped below a level of 0.002 U/ml, where CSTF is unlikely. Five of 13 BT-A-AB titres did not decrease. For three of these five, the monitoring period was less than 1,500 days; a chance to drop remained. The other two were monitored for up to 2,400 days. Patients with decreasing and nondecreasing BT-A-AB titres did not exhibit statistically significant differences in either clinical characteristics or treatment parameters. When BT-A therapy was stopped the majority of BT-A-AB titres eventually decreased, allowing reinitiation of BT-A therapy. Application of new BT-A preparations with low antigenic potency might then become an interesting treatment option.

Adult↗
PubMed2002

Botulinum toxin type B for treatment of axillar hyperhidrosis.

Recently, botulinum toxin type B (BT-B) became commercially available for treatment of cervical dystonia. It is the aim of this study to explore its use for treatment of bilateral axillar hyperhydrosis (HH). For this we directly compared the antihyperhydrotic effect of BT-B (NeuroBloc)/MyoBloc) with that of botulinum toxin type A (BT-A) (Botox). 9 patients (HD group) received BT-A 100MU unilaterally and BT-B 4000MU contralaterally. 10 patients (LD group) received BT-A 100MU and BT-B 2000MU. All patients were blinded as to which preparation was used in which side. All patients except one reported excellent HH improvement in both axillae. None of the patients had residual HH on clinical examination. The duration of HH improvement until first recurrence in the HD group was 16.0 +/-4.3 weeks in the BT-A treated axillar and 16.4 +/-4.5 weeks in the BT-B treated axillae (Wilcoxon rank-sum test, p = 0.336). In the LD group it was 16.4 +/-5.3 weeks in the BT-B treated axillae and 17.1 +/-5.7 weeks in the BT-A treated axillae (Wilcoxon rank-sum test, p = 0.059). There was also no difference in the duration of HH improvement between the axillae treated with BT-B 4000MU and BT-B 2000MU (Wilcoxon rank-sum test, p = 0.712). 5 out of 9 patients in the HD group (chi-square test, p = 0.025) and 7 out of 10 patients in the LD group (chi-square test, p = 0.008) reported more application discomfort in the BT-B treated axillae. In 6 out of 9 patients in the HD group (chi-square test, p = 0.014) and in 6 out of 10 patients in the LD group (chi-square test, p = 0.014) the onset of HH improvement appeared earlier in the BT-B treated axillae. One patient in the HD group reported dryness of the mouth and eyes and accomodation difficulties.BT-B is a safe and efficient treatment for axillar HH. Doses of BT-B 2000MU per axilla seem sufficient indicating a conversion factor between BT-A and BT-B in the order of 1:20. With a conversion factor for cervical dystonia in the order of 1:40 the autonomic nervous system seems to be relatively more sensitive to BT-B than to BT-A compared with the motor system.

Adult↗
PubMed2002

Antibody-induced botulinum toxin therapy failure: can it be overcome by increased botulinum toxin doses?

In some patients treated with botulinum toxin type A (BT) therapy failure occurs due to the formation of antibodies against BT (BT-AB). We investigated whether increased BT doses can overcome this form of therapy failure. Eight patients with cervical dystonia, secondary BT therapy failure and evidence of BT-AB formation in the mouse diaphragm bioassay received BT test doses (Dysport, Ipsen Ltd., Maidenhead, Berks, UK) into one of their sternocleidomastoid muscles. Test doses were increased in three steps at 3-month intervals and their effect on the amplitude of the electromyographic activity of the sternocleidomastoid muscle under maximal isometric activation (M-EMG) was measured and compared to a control group. In step 1 (200 or 300 MU) the M-EMG reduction was 12 +/- 13% compared to 85 +/- 10% (200 MU) and 83 +/- 9% (300 MU) in the control group. In step 2 (400, 600 or 800 MU) the M-EMG reduction was 25 +/- 21% compared to 78 +/- 7% (400 MU) in the control group. In step 3 (1,600 or 1,800 MU) the M-EMG reduction was 24 plus minus 10%. Side effects were not observed in any of the patients studied. In 1 patient with partial secondary BT therapy failure, with a low BT-AB titre (0.0015 U/ml) and with a moderately pathological M-EMG reduction of 40% with 200 MU a normal M-EMG reduction of 71% could be regained with 800 MU. In three subsequent therapeutic injection series with quadrupled BT doses in all target muscles the original therapy outcome could be regained and maintained. Side effects or increasing BT-AB titres were not observed. Even massively increased BT doses cannot overcome BT-AB-induced complete secondary therapy failure. However, in patients with partial secondary therapy failure, low BT-AB titres and a moderately pathological M-EMG reduction, increased BT doses might regain and maintain normal BT efficacy without induction of side effects or increasing BT-AB titres.

Adult↗
PubMed2002

Clinical features of antibody-induced complete secondary failure of botulinum toxin therapy.

In some patients treated with botulinum toxin type A (BT), secondary therapy failure occurs. It can either be partial (PSTF) or complete (CSTF). One of the main causes for CSTF is the formation of antibodies against BT. We wanted to study the clinical features of BT antibody-induced CSTF to improve its detection. For this, 27 patients with various dystonic syndromes and antibody- failure were studied. In 22 patients CSTF was preceded by a total of 63 injection series with PSTF. The number of injection series with preceding PSTF was 2.52 +/- 2.37 with a range from 0 to 8. When PSTF occurred, the maximal efficacy of BT therapy was reduced on 55 occasions and the efficacy duration on 48 occasions. CSTF occurred after treatment times of 61-1,507 days with grouping around 324.9 +/- 148.9 days and 1,155.7 +/- 436.8 days and patients with short interinjection intervals significantly overrepresented in the first group (Mann-Whitney U test, p = 0.009). Sex and age at initiation of BT therapy, single BT dose, and number of booster injection series were not different in both groups. Immunological complications could not be detected in any of the patients. Clinical features of antibody failure described in this study show that the shorter the interinjection intervals, the earlier antibody failure occurs. They make it highly unlikely for patients with long-standing BT therapy to develop antibody failure, and they might be useful to identify antibody failure before elaborate BT antibody testing is initiated.

Adult↗
PubMed2002

Expression of retinoid-related genes in serum-free cultures of normal, immortalized and malignant human oral keratinocytes.

Retinoids are used in the clinical treatment of oral squamous carcinoma, including both early and late stages. Inter-individual variation in responsiveness, including a common insensitivity of advanced stages, suggest that changes in retinoid-related functions might characterize tumor development. To investigate a genetic basis for this hypothesis, an in vitro multi-step model of carcinogenesis involving normal (NOK), SV40 T antigen-immortalized (SVpgC2a) and malignant (SqCC/Y1) oral keratinocytes was analysed under identical culture conditions using micro-array technique (Affymetrix HG_U95A chip) for expression of 52 genes related to retinoid metabolism and actions. The variable detection of between 22-26 transcripts in the cell lines, involving binding/transport factors, receptors, transcriptional activators/repressors and responsive genes, indicated specificity in regards to the expression of known retinoid-related genes in oral keratinocytes. The transformed cell lines variably exhibited differences as compared to NOK, i.e., lower transcript levels for cellular retinol binding protein, the cellular retinoic acid binding protein II (CRABP II) and retinoic acid receptor gamma, whereas in contrast, the levels of CRABP I were higher. Transcripts for proteins interacting with nuclear retinoid receptors were similarly expressed among the cell types, whereas transcripts for retinoid-metabolizing enzymes were generally not detected. Finally, transcripts of retinoid-responsive genes, including RARRES3, RI58, NN8-4AG and midkine, were variably expressed. The overall results imply selective expression of retinoid-related functions in normal and transformed keratinocytes, and that cell transformation can impair the capacity for binding and storage of retinol as well as retinoic acid-mediated signalling. These multiple alterations are consistent with possible retinoid insensitivity during oral carcinogenesis.

Cell Line↗