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Biomedical subjects

B Schmitz

Publications and source records attributed to B Schmitz.

At least 19 recordsLinked to original sources

[The use of lamotrigine in female patients].

BACKGROUND: Gender aspects are important when assessing the tolerability of antiepileptic drugs (AED). Due to its broad spectrum of action and to the lack of evidence for teratogenicity in monotherapy, lamotrigine (LTG) is an AED of first choice for women with epilepsy with child-bearing potential. METHOD: In an observational study over 6 months including 832 women with epilepsy, we evaluated the efficacy and tolerability of LTG in monotherapy and add-on therapy, with a special focus on parameters of particular importance for women including changes in weight, skin, hair, and patterns of menstruation. RESULTS: Of the treated patients, 94% had seizure reduction of at least 50%. Adverse events occurred in 7.3%; 1% experienced serious adverse events, all of which were reversible. Ninety-six percent continued treatment throughout the observation period, and 83% reported improvement in quality of life by the end of the study. Cognition, functioning at work, and mood improved in 43-54% of patients. In most of them, weight remained stable. Those who were switched from valporate (VPA) or carbamazepine (CPZ) to LTG lost 3.2 kg and 3.1 kg (means), respectively. Many of the women described problems related to menstruation at the beginning of the study: variability in cycle length (31.2%), hypermenorrhea (17.3%), and pains (10%). Skin and hair problems were reported by 18.4% and 17.3%, respectively. There was improvement in all of these aspects at the end of the study, particularly for those women switched from VPA or CBZ to LTG. CONCLUSION: In summary, this observational study confirms the good tolerability of LTG with respect to issues particularly relevant to women. More complete elucidation of the correct LTG dosage, which varies widely according to the accompanying medication, will further improve treatment safety.

Acne Vulgaris↗

[EURAP: the European Registry of Antiepileptic Drugs and Pregnancy].

All old-generation antiepileptic drugs (AEDs) are considered to be teratogenic. In Germany, one out of 200 pregnant women (0.5%) is treated with AEDs for epilepsy. The risk of major malformations following exposure to AEDs during the first trimester of pregnancy is two to three times the rate reported in the general population, which is estimated at 2-3%. The risks associated with the treatment of epilepsy during pregnancy are therefore of major concern to all women of childbearing potential with epilepsy. Data on the comparative teratogenicity of these AEDs in humans are, however, conflicting, mainly due to inadequate sample sizes and other methodological shortcomings of previous studies. The teratogenic potential of newer AEDs is even less well known, which prevents a rational approach to AED treatment in women of childbearing potential. The European Registry of Antiepileptic Drugs and Pregnancy is a prospective international multicentre study of pregnancies with AEDs. In Germany the project was started in 2001 and so far more than 500 pregnancies have been enrolled. The enrollment rate is 4% of 4,000 pregnancies with AEDs reported annually.

Abnormalities, Drug-Induced↗

[Neuropsychological outcome following intrauterine exposure to valproate].

A number of recent studies suggest a link between in utero exposure to valproate (VPA) and low IQ and behavioural disorders in children of mothers with epilepsy. In this review, a commission of the German Section of the International League Against Epilepsy discusses the evidence in the literature and practical recommendations for the use of VPA in women of childbearing potential. It is concluded that despite methodological shortcomings--largely due to the complexity of the problem and small case numbers in prospective studies--the existing data are sufficiently alarming to require great caution in the use of VPA in women who could become pregnant. The underlying mechanisms of how antiepileptic drugs may lead to neurodevelopmental problems are unclear. Further prospective studies are urgently needed to clarify this clinically important issue, and a collaborative study is suggested based on the international network established by the European Registry of Antiepileptic Drugs and Pregnancy.

Female↗

Role of valproate across the ages. Treatment of epilepsy in adults.

A workshop was held in Göteborg in June 2005 to discuss the place of valproate in treating adult epilepsies. Consensus positions were developed on the epilepsy types for which the drug is most suitable and the use of valproate in women of child-bearing age, in men and in patients with psychiatric comorbidity. Valproate was considered to be effective across a broad variety of epilepsy syndromes and seizure types and should be considered a suitable choice for first-line monotherapy of juvenile myoclonic epilepsy and other idiopathic generalized epilepsies. The use of valproate by women of child-bearing age is associated with potential harm to the foetus. A conservative approach to treatment is recommended in these patients whereby alternative antiepileptic drugs should be proposed to women planning pregnancies wherever satisfactory seizure control can be thereby maintained. In cases where valproate is used during pregnancy, either because the pregnancy was unplanned or because alternative treatment options of equivalent efficacy are unavailable, appropriate counselling, precautionary measures and monitoring should be provided. The evidence for an impact of valproate on male reproductive health is equivocal and considerations of male fertility should not be taken into account in deciding whether to prescribe valproate to men. Valproate can be proposed safely to patients with comorbid psychiatric disease or underlying psychiatric vulnerability.

Adult↗

Supportive evidence for an allelic association of the human KCNJ10 potassium channel gene with idiopathic generalized epilepsy.

PURPOSE: Quantitative trait loci (QTL) mapping in mice revealed a seizure-related QTL (Szs1), for which the inward-rectifying potassium channel Kcnj10 is the most compelling candidate gene. Association analysis of the human KCNJ10 gene identified a common KCNJ10 missense variation (Arg271Cys) that influences susceptibility to focal and generalized epilepsies. The present replication study tested the initial finding that the KCNJ10 Cys271 allele is associated with seizure resistance to common syndromes of idiopathic generalized epilepsy (IGE). METHODS: The study sample comprised 563 German IGE patients and 660 healthy population controls. To search for seizure type-specific effects, two IGE subgroups were formed, comprising 258 IGE patients with typical absences (IAE group) and 218 patients with juvenile myoclonic epilepsy (JME group). A TaqMan nuclease assay was used to genotype the KCNJ10 single nucleotide polymorphism c.1037C > T (dbSNP: rs1130183) that alters amino acid at position 271 from arginine to cysteine. RESULTS: Replication analysis revealed a significant decrease of the Cys271 allele frequency in 446 IGE patients compared to controls (chi2 = 3.52, d.f. = 1, P = 0.030, one-sided; OR(Cys271+) = 0.69; 95% CI: 0.50-0.95). Among the IGE subgroups, lack of the Cys271 allele was accentuated in the JME group (chi2 = 5.20, d.f. = 1, P = 0.011, one-sided). CONCLUSION: Our results support previous evidence that the common KCNJ10 Arg271Cys missense variation influences seizure susceptibility of common IGE syndromes.

Alleles↗

Filtering bleb function after clear cornea phacoemulsification: a prospective study.

AIM: To evaluate the influence of clear cornea phacoemulsification on filtering bleb morphology, function, and intraocular pressure (IOP) in glaucomatous eyes with previously successful filtering surgery. METHODS: The clinical course of 30 patients (30 eyes) who underwent clear cornea phacoemulsification after successful filtering glaucoma surgery was prospectively evaluated. Mean IOP and filtering bleb morphology (standardised assessment criteria and score 0-12, 12 = optimum) were determined before surgery, and 3 days, 6 months, and 12 months after surgery. The control group consisted of 36 patients with glaucoma after clear cornea phacoemulsification without previous filtering surgery. RESULTS: Mean IOP increased after phacoemulsification by about 2 mm Hg (preoperatively 14.28 (SD 3.71) mm Hg, 12 months postoperatively 16.33 (3.31) mm Hg, p = 0.006). 15 patients (50%) showed an IOP increase of >2 mm Hg, 11 patients (36.7%) had no IOP difference (within 2 mm Hg), and in four patients (13.3%) IOP decreased >2 mm Hg. Mean score of filtering bleb morphology 1 year after surgery decreased from 9.5 to 9.0 (p = 0.154). In three of 30 preoperatively IOP regulated eyes the postoperative IOP was 21 mm Hg. The control group showed an average IOP decrease of 2.01 mm Hg (p = 0.014) 12 months after cataract surgery. CONCLUSION: An increase in IOP was found 1 year after phacoemulsification in half of the filtered glaucomatous eyes. IOP in glaucomatous eyes without previous filtering surgery decreased in the same period. Cataract extraction using clear cornea phacoemulsification may be associated with a partial loss of the previously functioning filter and with an impairment of filtering bleb morphology.

Aged↗

Lateralization in autonomic dysfunction in ischemic stroke involving the insular cortex.

Autonomic nervous system dysfunction is a common complication of ischemic stroke. Clinical and experimental data indicate hemispheric lateralization in the control of autonomic activity. The insular cortex has also been shown to play a crucial role in the central autonomic network. The aim of this study was to assess cardio-autonomic dysfunction in patients with ischemic insular versus non-insular cortex infarction, and to demonstrate a possible lateralization in autonomic activity mediated by the insular cortex. Sympathetic function was prospectively assessed by determining plasma norepinephrine and epinephrine in 15 patients with left-hemisphere (LH; four insular infarction), and 14 with right-hemisphere (RH) middle cerebral artery (MCA) stroke (five insular infarction). Systolic and diastolic blood pressure and heart rate were recorded during the first 5 days after stroke. Sympathetic activity was significantly higher in insular than in non-insular infarction (p < 0.05) with concomitantly elevated cardiovascular parameters in insular stroke patients. The pathological activation of the sympathetic nervous system was most excessive in RH-stroke involving the insular cortex (p < 0.05). Our data indicate a hemispheric lateralization in autonomic activity which is mediated by the right-sided insular cortex. Patients with RH stroke involving the insular cortex are most susceptible to develop cardio-autonomic dysfunction.

Aged↗

Variation of endplate thickness in the cervical spine.

The purpose of the study was to investigate possible variation of thickness of the cervical spine endplate with respect to endplate orientation (superior or inferior endplate) and level distribution (C4-C7). Six human cervical spine segments C4-C7 were used to create six specimen of C4, C5, C6, and C7, respectively. The bony endplates of each vertebra were cleaned carefully from disc tissue without damaging the endplates. Six endplates with severe degenerative changes were excluded from the study. The posterior elements were removed, and a midaxial cut using a bone saw was performed through each vertebral body, thus producing a superior and inferior half. Each half-vertebra was then glued onto a piece of wood with the endplate oriented upwards and horizontally. For each specimen, four computed tomography scans were taken and thickness of the endplate was measured at five points on each scan perpendicular to the midaxial cut. Factorial analysis of variance (ANOVA) and Scheffe-test were used to detect significant differences. All peripheral regions were significantly thicker than the central point of the endplate if all measuring points were considered for statistical analysis, regardless of scan, endplate orientation or level (Scheffe-test, P<0.001). In both superior and inferior endplates, peripheral areas were thicker than the central region (Scheffe-test, P<0.001). For all levels, the endplate within the peripheral regions was thicker than within the central region and the difference reached significance for the superior and inferior endplate of C4, C5, and C6 and the inferior endplate of C7 (Scheffe-test, P<0.05). The peripheral regions of the cervical spine endplate are usually thicker than its central region, regardless of endplate orientation and level (C4, C5, C6, C7) distribution.

Aged↗

Regional variations in the thickness of cervical spine endplates as measured by computed tomography.

PURPOSE: To determine regional variations in the thickness of human cervical spine endplates with high spatial resolution. MATERIAL AND METHODS: Six explanted human cadaveric spine specimens underwent computed tomography (CT) scanning. Measurement of endplate thickness was done fully automatically at every point of the endplate using a computer program written specifically for this purpose. Variations in thickness along sagittal and coronal lines were determined and statistical parametric mapping was used to test for significant regional variations at every point. RESULTS: Anterior and medial aspects of superior endplates were shown to be significantly thinner than lateral and dorsal parts. Superior endplates were found to be thicker than inferior endplates. CONCLUSION: Fully automatic assessment of endplate thickness from CT data is feasible. Central regions of the cervical spine endplates are thinner than peripheral parts of the endplates. This distribution is more pronounced in superior than in inferior endplates.

Algorithms↗

Three-dimensional true FISP for high-resolution imaging of the whole brain.

While high-resolution T1-weighted sequences, such as three-dimensional magnetization-prepared rapid gradient-echo imaging, are widely available, there is a lack of an equivalent fast high-resolution sequence providing T2 contrast. Using fast high-performance gradient systems we show the feasibility of three-dimensional true fast imaging with steady-state precession (FISP) to fill this gap. We applied a three-dimensional true-FISP protocol with voxel sizes down to 0.5 x 0.5 x 0.5 mm and acquisition times of approximately 8 min on a 1.5-T Sonata (Siemens, Erlangen, Germany) magnetic resonance scanner. The sequence was included into routine brain imaging protocols for patients with cerebrospinal-fluid-related intracranial pathology. Images from 20 patients and 20 healthy volunteers were evaluated by two neuroradiologists with respect to diagnostic image quality and artifacts. All true-FISP scans showed excellent imaging quality free of artifacts in patients and volunteers. They were valuable for the assessment of anatomical and pathologic aspects of the included patients. High-resolution true-FISP imaging is a valuable adjunct for the exploration and neuronavigation of intracranial pathologies especially if cerebrospinal fluid is involved.

Adult↗

[Lamotrigine in women with epilepsy. Review of present data].

The manuscript deals with the tolerability of Lamotrigine in women. The recent literature is reviewed with respect to interactions with oral contraceptives, sexuality, infertility, interactions with sex hormones, polycystic ovarian syndrome, adipositas, cosmetic side effects, osteoporosis, pregnancy, breast feeding, and teratogenetic effects. The available data have practical implications for the safe use of Lamotrigine in women.

Abnormalities, Drug-Induced↗

N-glycosylation patterns of HSA/CD24 from different cell lines and brain homogenates: a comparison.

N-glycans of the mouse glycoprotein HSA and its human analogue CD24 from lymphoblastoma, neuroblastoma and astrocytoma cell lines as well as from mouse brain homogenate were analysed and compared to each other and to the N-glycosylation pattern of total glycoproteins from mouse and human brain. The N-glycans were released from PVDF-blotted HSA or CD24 and separated on Carbograph SPE into neutral and acid glycans. The naturally neutral glycan fraction and the fraction of glycans rendered neutral after neuraminidase treatment were analysed without further purification by MALDI-MS. In each fraction, about 25 molecular ions with an intensity >10% of the base peak were identified which corresponded to glycans with distinct isobaric monosaccharide compositions. Comparison of the neutral and desialylated glycans revealed some similarities between the samples analysed, but also clear differences. HSA and CD24 from all cell lines express almost no neutral N-glycans with two or more fucose in contrast to brain HSA and glycoproteins from mouse and human brain. The lack of extensive fucosylation was also observed for desialylated glycans of HSA and CD24 from all cell lines analysed except for CD24 from a human neuroblastoma cell line which exhibits like total human and mouse brain glycoproteins a large variety of highly fucosylated, higher branched N-glycans. HSA from mouse brain carries in addition desialylated non-fucosylated glycans of high abundance which were detected, if at all, only at low intensity in all other samples analysed suggesting that they may be implicated in specific functions of mouse brain HSA. Therefore, a rapid assessment of similarities or differences between glycosylation patterns of a glycoprotein isolated from different sources is possible using methods as described here.

Animals↗

Epilepsy, antiepileptic drugs (AEDs) and cognition.

People with epilepsy are at increased risk of cognitive deficits as a result of various factors: the effect of seizures themselves, psychosocial factors and adverse effects of AEDs. It is crucial that, following early diagnosis of the correct epileptic syndrome, patients are treated with the appropriate drugs, as incorrect AEDs can exacerbate symptoms. By discussing various epileptic syndromes and performing a broad review of the available evidence, it is possible to make recommendations concerning prescription of AEDs with respect to cognition. An interesting advance in this area is the increasing use of AEDs such as valproate (in some countries divalproex is indicated), carbamazepine or lamotrigine (lamotrigine has been filed for approval in this indication) for bipolar disorders. Children and the elderly are especially vulnerable to adverse effects on cognition. This review highlights advantages of valproate in these populations; it is well tolerated and produces few cognitive side effects.

Adolescent↗

Location-dependent patterns in cardio-autonomic dysfunction in ischaemic stroke.

BACKGROUND AND STUDY PURPOSE: Autonomic nervous system dysfunction is a common complication of acute cerebrovascular disorders. The aim of this study was to investigate a possible location-dependent difference in cardio-autonomic function in patients with ischaemic stroke. PATIENTS AND METHODS: Sympathetic function was prospectively assessed by determining plasma norepinephrine and epinephrine in 19 patients with left-hemisphere (LH), 14 with right-hemisphere (RH) and 6 with brainstem/cerebellar (BS) stroke. Blood pressure, heart rate, cardiac output and transcranial flow velocity in the middle cerebral artery were recorded during the first 5 days after stroke. RESULTS: Stroke caused an initial increase in sympathetic function in all 3 groups with a spontaneous decrease in norepinephrine in LH (p < 0.01) and BS stroke (p < 0.05) only. Norepinephrine was significantly higher in RH than in BS stroke (p < 0.05). The alterations in autonomic function were paralleled by a sustained elevation in cardiovascular parameters mainly in RH stroke. CONCLUSIONS: Plasma catecholamines are feasible in monitoring location-dependent autonomic dysfunction in ischaemic stroke. Hemispheric lateralization in autonomic control should be taken into account in the management of stroke because of an increased susceptibility to cardio-autonomic dysfunction in patients with RH stroke.

Aged↗

Is visual field constriction in epilepsy patients treated with vigabatrin reversible?

OBJECTIVE: To evaluate the reversibility of vigabatrin associated visual field constriction. BACKGROUND: Visual field constriction (VFC) occurs in approximately 40 % of epilepsy patients under treatment with vigabatrin (VGB). There is still controversy about whether VGB-associated VFC is reversible. From a cross-sectional study there is evidence that VFC does not reverse three to six months after stopping VGB treatment. So far, there are no long term studies on this subject. METHODS: We performed a follow-up study on 15 epilepsy patients (eight women, seven men, median age 45 (21-58) years) with VGB-associated VFC but otherwise normal ophthalmological examination. Kinetic and static perimetry was performed one and two years after VFC was diagnosed (baseline examination). Visual field size at first and at second year-follow-up was compared with the baseline examination. Because discontinuation of VGB-treatment was dependant on clinical needs, patients either stopped VGB treatment before or after VFC was diagnosed. In a small group of patients VGB treatment was continued despite of VFC. RESULTS: There was no statistically significant difference in visual field size comparing baseline values with first year and second year follow-up examinations either in patients who stopped VGB treatment (n = 11) or in patients who continued VGB treatment on a reduced dosage (n = 4). CONCLUSION: Although our data are based on a relatively small group of patients there is evidence that VFC resulting from VGB treatment is not reversible in epilepsy patients after stopping the drug.

Adult↗

Visual field constriction in epilepsy patients treated with vigabatrin and other antiepileptic drugs: a prospective study.

BACKGROUND: Visual field constriction (VFC) has been described in about 30 % to 50 % of patients treated with the antiepileptic drug (AED) Vigabatrin (GVG). The exact incidence of VFC related to GVG exposure is unknown. Risk factors other than medication have not been identified as yet, and it is unclear whether the occurrence of VFC is restricted to the use of GVG. METHODS: In a longitudinal study, we investigated 60 epilepsy patients who received GVG and other AEDs. Patients underwent full ophthalmological examination including perimetry. RESULTS: 16 of 60 patients exposed to different AEDs developed VFC, which was judged as clinically relevant by an experienced neuroophthalmologist. VFC was observed significantly more often in patients treated with GVG as add-on- or monotherapy as compared with patients who had never been exposed to GVG (13/29 versus 3/31). Within the subgroup of 23 patients who received GVG as add-on therapy, those who developed VFC had been exposed to GVG for significantly longer than patients without VFC. The only non-treatment related feature associated with VFC was older age. Type and severity of epilepsy or type and number of concomitant AED were not related to the occurrence of VFC. CONCLUSIONS: The findings of an overrepresentation of VFC in patients receiving GVG and of a correlation between duration of GVG treatment and occurrence of VFC support the causal role of GVG treatment in the development of VFC. Old age is a possible risk factor for the development of VFC associated with GVG in epilepsy patients.

Adult↗

Snapping shrimp make flashing bubbles.

Snapping shrimp produce a loud crackling noise that is intense enough to disturb underwater communication. This sound originates from the violent collapse of a large cavitation bubble generated under the tensile forces of a high-velocity water jet formed when the shrimp's snapper-claw snaps shut (Fig. 1). Here we show that a short, intense flash of light is emitted as the bubble collapses, indicating that extreme pressures and temperatures of at least 5,000 K (ref. 4) must exist inside the bubble at the point of collapse. We have dubbed this phenomenon 'shrimpoluminescence' - the first observation, to our knowledge, of this mode of light production in any animal - because of its apparent similarity to sonoluminescence, the light emission from a bubble periodically driven by ultrasound.

Animals↗