Biomedical subjects

M Dam

Publications and source records attributed to M Dam.

At least 19 recordsLinked to original sources

PubMed1999

Identification of 19 polybrominated diphenyl ethers (PBDEs) in long-finned pilot whale (Globicephala melas) from the Atlantic.

Nineteen tetra- to hexabrominated diphenyl ethers were identified at ppb concentration in the blubber of pilot whale caught off the coast of the Faroe Islands in 1994 and 1996. Higher total concentrations were found in the pooled samples of young males (3,160 ng/g lipid) and females (3,038 ng/g lipid) compared to adult females (843 ng/g and 1,048 ng/g lipid) and males (1,610 ng/g lipids). The predominant isomers in all samples were 2,2',4,4'-TeBDE (PBDE #47) and 2,2',4,4', 5-PeBDE (PBDE #99) accounting for some 70% of the sum of the 19 isomers.

Adipose Tissue↗

PubMed1999

Fracture risk is increased in epilepsy.

OBJECTIVES: To study fracture rates and risk factors for fractures in non-institutionalized patients with epilepsy. MATERIAL AND METHODS: Historical follow-up. Self-administered questionnaires were issued to 755 patients with epilepsy (ICD 10: G40.0 to G40.9) and 1000 randomly selected controls from the background population. RESULTS: A total of 345 patients (median age: 45, range 17-80 years) and 654 control subjects (median age: 43, range 19-93 years) returned the questionnaire. Before epilepsy was diagnosed there was no difference in overall fracture rate between patients and controls (RR = 1.0, 95% CI: 0.8-1.3). After the diagnosis the overall fracture rate was significantly higher in the patients (RR = 2.0, 95% CI: 1.6-2.5). Fractures of the spine, forearms, femurs, lower legs, and feet and toes were significantly increased. Fractures related to seizures accounted for 33.9% (95% CI: 25.3-43.5%) of all fractures. After elimination of seizure related fractures the increase in fracture frequency was only borderline significant: RR = 1.3 (95% CI: 1.0-1.7, P = 0.042). No difference in fracture energy between patients and controls was observed (low energy fractures: 1.7/1.4%, medium energy fractures: 59.8/52.0%, and high energy fractures: 38.3/46.6%). Use of phenytoin (OR = 2.4, 95% CI: 1.1-5.4) and a family fracture history (OR = 2.4, 95% CI: 1.3-4.6) was associated with an increased fracture risk. CONCLUSIONS: Fractures were more common in epileptics than in controls especially among users of phenytoin. Most of the increase in fracture frequency was related to seizures and not to low bone biomechanical competence.

Adolescent↗

PubMed1999

Electroencephalography in dogs with epilepsy: similarities between human and canine findings.

OBJECTIVES: To investigate the diagnostic value of electroencephalography (EEG) in dogs with epilepsy, applying human criteria for EEG abnormalities observed with this disorder. MATERIAL AND METHODS: Twenty-six dogs with a clinically established diagnosis of epilepsy were investigated with electroencephalography (EEG) in order to evaluate the diagnostic yield of EEG in canine epilepsy. RESULTS: Of 23 dogs with evaluable EEGs 15 (65%) demonstrated abnormal activity. The most common abnormalities were focal low frequency patterns without spikes (48%), followed by focal epileptiform activity (22%) and generalized epileptiform activity (17%). The distribution between focal and generalized activity were 73% and 27%, respectively. Consistency were demonstrated between the clinical- and the EEG-diagnosis in 13 dogs (87%). A relationship was demonstrated between the number of abnormal EEGs and the proximity of a seizure to the EEG examination. CONCLUSION: A marked consistency was demonstrated between the clinical diagnosis of seizure type and the type of abnormalities observed in the EEG, thus indicating that EEG is a valuable diagnostic aid in confirming the diagnosis of epilepsy in dogs. EEG findings in dogs with epilepsy and humans with this disorder were markedly similar.

Animals↗

PubMed1998

Regional cerebral blood flow changes in patients with cirrhosis assessed with 99mTc-HM-PAO single-photon emission computed tomography: effect of liver transplantation.

BACKGROUND/AIMS: Previous studies showed contrasting results with regard to alterations of regional cerebral blood flow/metabolism in subjects with liver cirrhosis. The aim of the study was to extend these findings in a larger series of patients. In addition, we wanted to determine whether such alterations are reversed by successful liver transplantation. METHODS: The study group comprised 23 patients with liver cirrhosis and 13 normal controls. At entry to the study, all subjects underwent a complete neurological examination, EEG recordings and SPECT scanning. The severity of liver disease was determined according to the Child-Pugh score. Fourteen patients underwent a second SPECT examination 1 year after liver transplantation. RESULTS: Significant rCBF reductions, ranging from 6% to 7%, were found in the majority of the cortical regions of the whole group of patients with cirrhosis, as compared to controls. These reductions were more diffuse in patients with alcoholic liver disease, comprising almost all the assayed regions. Liver transplantation normalized cortical rCBF deficits so that postoperative perfusion indexes were superimposable on control values. However, the frontal cortex remained significantly more impaired in patients with alcoholic cirrhosis than in those with non-alcoholic cirrhosis. The differences in frontal rCBF between the two groups of patients ranged from 6 to 11%. CONCLUSIONS: Liver cirrhosis was associated with rCBF defects that depend upon the etiology of liver disease and that subsided after successful liver transplantation. The frontal defects in alcoholic cirrhosis either before or after surgery may imply a neurotoxic, possibly irreversible, action of ethanol.

Adult↗

PubMed1998

Pregnancy and epilepsy: a retrospective study of 151 pregnancies.

OBJECTIVE: We studied the course of pregnancy in women with epilepsy to identify possible risk factors which might complicate the epilepsies and pregnancy outcomes. MATERIAL AND METHODS: Data were collected retrospectively from the records of 151 pregnancies in 124 women with epilepsy from 1978-1992. Epilepsy variables were compared with that of non-pregnant women with epilepsy matched for age. Obstetric and neonatal variables were compared with those of all deliveries in the same unit from 1979-1992 (n=38,983). RESULTS: Pregnancy among patients with epilepsy was more likely to occur in women with relatively mild epilepsy. In 12% of the pregnancies, the women were untreated while 71% were on monotherapy. Twenty-one percent had increased seizure frequency during the pregnancy. Perinatal deaths among newborns of epileptic mothers (1.3%) was more frequent but not significantly increased compared to the background population of 0.5% (95% CI 0.2-4.7). A total of 5.3% had congenital malformations compared to 1.5% in the controls (95% CI 2.3-10.3). No neural tube defects were observed. Maternal treatment with phenytoin was significantly related to the occurrence of congenital malformations, P=0.04. CONCLUSIONS: Most women with epilepsy have an uncomplicated pregnancy and normal healthy offsprings. Maternal treatment with phenytoin might be associated with congenital malformations. No other risk factors could be identified.

Abnormalities, Drug-Induced↗

PubMed1998

Anticipation in familial cavernous angioma: ascertainment bias or genetic cause.

OBJECTIVES: Anticipation has been linked to unstable trinucleotide repeats in many neurological disorders. We examined the hypothesis of genetic anticipation in familial cavernous angioma (FCA) of the central nervous system. MATERIAL AND METHODS: The mean ASO of affected individuals was compared between successive generations in 55 families. Intergenerational pair-wise comparisons were employed to avoid several ascertainment biases. Regarding severity of disease both type of manifestation and number of cavernous angiomas were compared between generations. RESULTS: The mean ASO decreased significantly both from the first to the second generation (31.6 vs 17.8 years; P = 0.000) and from the second to the third generation (17.8 vs 6.7 years; P = 0.002). The pair-wise comparisons also showed significantly earlier ASO. No clear evidence for anticipation with regard to severity of disease was found. CONCLUSIONS: Molecular genetic studies will determine whether trinucleotide repeats are the underlying mechanism for our observation of anticipation in FCA.

Adolescent↗

PubMed1997

The effects of propofol on cerebral high energy metabolites, lactate, and glucose in normoxic and severely hypoxic rats.

Study was performed in Fischer-344 rats to test the effects of the intravenous anesthetic propofol on cerebral content of high-energy metabolites, glucose, and lactate in normoxic and severely hypoxic rats. General and local anesthetics (isoflurane, N(2)O 70%, pancuronium bromide, bupivacaine hydrochloride) were used for surgery (tracheostomy, femoral artery and vein cannulation, skull exposure, ligature of right-sided carotid and EEG needle electrodes only in rats devoted to the hypoxia study). For normoxia study, four groups of 7 rats each were treated for 60 min as it follows: the control group with N(2)O plus propofol vehicle and the other three with propofol 12.5, 25, or 50 mg x kg(-1) x h(-1) respectively. For the hypoxia-study five groups of 7 rats each were planned to have two control (one normoxic) and three propofol-treated groups, drug treatments being the above indicated and of 80 min. During the last 20 min Pa(O(2)) was lowered to 15-20 mmHg. Pa(CO(2)) was maintained between 35-40 mmHg, rectal temperature at 37 degrees C, MABP near to 100 mmHg and pH on the basal values during the whole procedure. Then brains were frozen in vivo, and cortical tissue was excised and analyzed for labile metabolites using fluorometric techniques. Propofol, at all the doses tested, did not alter the concentrations of adenine nucleotides, phosphocreatine, lactate, pyruvate, or glucose in normoxic rats. In rat brain, hypoxia did not produce significant changes in the concentrations of adenine nucleotides. PCr concentration was decreased both in the ligated and unligated side, and lactate levels exceeded 21 and 18 micromol/g in the right and left cortices, respectively. While the lowest dose of propofol was ineffective in preventing PCr decrease and lactate increase, both 25 and 50 mg x kg(-1) x h(-1) significantly reduced those adverse effects of hypoxia.

Adenine Nucleotides↗

PubMed1997

ECG changes in epilepsy patients.

OBJECTIVES: To investigate the frequency of ECG abnormalities suggestive of myocardial ischaemia in patients with severe drug resistant epilepsy and without any indication of previous cardiac disease, assuming that these changes may be of significance for the group of epileptic patients with sudden unexpected death. MATERIAL AND METHODS: Twelve patients with medically intractable epilepsy were investigated with simultaneous long ECG and EEG recordings while attending either epilepsy surgery investigational procedures or the investigational programme for diagnostic purposes, and one while having an episode of status epilepticus. RESULTS: The ECG recording failed in 1 patient. This patient had chest pain and minor yet morphologically conspicuous changes in the ECG, suggestive of myocardial infarction. He died in heart arrest. Eight epilepsy patients had episodes of ST segment depression in the ECG, many of which coincided with video- and EEG documented epileptic seizures. Two patients experiencing simple partial seizures and 1 patient experiencing absence seizures had no ST segment depressions in the ECG. One patient had an episode of status epilepticus secondary to brain damage and no ST segment deviation was seen during the ECG recording which continued until 3 h before the patient died. CONCLUSION: Patients with severe drug resistant epilepsy have episodes of ST segment changes, some of which are closely related to epileptic seizures. Further studies are needed to confirm the present results and to investigate the nature of these changes and document the effect of prophylactic treatment with cardioactive drugs to reduce the risk of sudden death.

Adolescent↗

PubMed1996

Mutations in domain II of 23 S rRNA facilitate translation of a 23 S rRNA-encoded pentapeptide conferring erythromycin resistance.

Mutations in domain II of Escherichia coli 23 S rRNA that cause resistance to erythromycin do so in a manner fundamentally different from mutations at the drug binding site in domain V of the 23 S rRNA. The domain II mutations are located in a hairpin structure between nucleotides 1198 and 1247. This is close to a short open reading frame in the 23 S rRNA that encodes a pentapeptide (E-peptide) whose expression in vivo renders cells resistant to erythromycin. Therefore, a possible mechanism of resistance caused by domain II mutations may be related to an increased expression of the E-peptide. To test this hypothesis, a range of point mutations was generated in domain II of 23 S rRNA in the vicinity of the E-peptide open reading frame. We find a correlation between erythromycin resistance of the mutant clones and increased accessibility of the ribosome binding site of the E-peptide gene. Furthermore, the erythromycin resistance determinant in the mutants was shown to be confined to a small 23 S rRNA segment containing the coding region and the ribosome binding site of the E-peptide open reading frame. It thus appears that the domain II mutations mediate erythromycin resistance by increasing expression of the 23 S rRNA-encoded E-peptide.

Base Sequence↗

PubMed1996

[Surgical treatment of epilepsy].

Patients with drug resistant frequent partial seizures rarely remit despite intensive drug treatment. On the contrary, seizures provoke neuronal loss with early mental deterioration and increased mortality. An exact localization of a resectable epileptogenic focus can offer a curative treatment. Mesial temporal sclerosis and lesional cortical partial epilepsy may indicate surgical therapy, both offering freedom of seizures in 50-90% of the patients. Non-lesional cortical partial epilepsy is more problematic, as only 30-40% of the patients will be seizure-free. Volumetric MR investigations, T2 relaxation time measurement and magnetic resonance spectroscopy together with other non-invasive methods have reduced the need for invasive investigations. As the best results are often achieved in children with their greater brain plasticity, surgical therapy should also be considered in children below the age of 12. This will prevent development of their role as chronically ill patients with the known accompanying psychological handicaps.

Adult↗

PubMed1996

[Lamotrigine treatment of 92 patients with intractable epilepsy].

The efficacy of treatment with lamotrigine (LTG) was evaluated in 92 patients with refractory epileptic seizures (46 women and 46 men aged 14-80 years, median 32 years). Seventy-one patients had partial epilepsy and 21 had primary generalized epilepsy. Patients were treated from zero to four (most frequently two) other antiepileptic drugs (AEDs). Maintenance dose of LTG was 50-800 mg daily (median 300 mg). Fifteen percent of the patients became seizure-free (13% of patients with partial epilepsy, 24% with primary generalized epilepsy). Thirty-eight percent of patients experienced at least 50% reduction in seizure frequency. Twenty-six percent of patients had a significant increase in seizure frequency (the same percentage in the two groups). Adverse events were recorded in 61% of patients, but most symptoms disappeared after dose reduction in concomitant AEDs. LTG was discontinued in 22% of patients, either because of adverse events or lack of effect. We conclude, that LTG is effective in reducing seizure frequency in patients with therapyresistant primary generalized epilepsy or partial epilepsy. Toxicity appears to be limited.

Adolescent↗

PubMed1996

Corpus callosotomy: seizure and psychosocial outcome. A 39-month follow-up of 20 patients.

The aim of the present study was to investigate the effect of corpus callosotomy on seizures, with emphasis on the psychosocial outcome. Data were retrospectively obtained from 20 patients (mean age 20.8 years, range 6-46). Sixteen of the operated patients took part in the 39-month (range 19-62) follow-up. Outcome measures were post-operative seizures, changes in the antiepileptic drug treatment, surgical complications including disconnection syndrome, degree of dependency according to the Barthel index, quality of life, burden on caretakers and satisfaction with the treatment. Half of the patients had a favorable seizure outcome, and of these 50% noticed an improved quality of life and were satisfied with the treatment. Four patients suffered from symptoms of cerebral disconnection syndrome which interfered with the activities of daily life. One patient died of complications 3 months after the operation. There were no significant changes in antiepileptic drug treatment, the patients' social lives or the burden of the patients on the caretakers. The conclusion is that prospective studies are needed to clarify the criteria for optimal patient selection to increase the likelihood of a positive psychosocial outcome.

Adolescent↗

PubMed1996

A randomised open multicentre comparative trial of lamotrigine and carbamazepine as monotherapy in patients with newly diagnosed or recurrent epilepsy.

The efficacy and safety of lamotrigine and carbamazepine as monotherapy in patients with untreated, newly diagnosed or recurrent partial and/or generalised tonic-clonic seizures, were compared in a randomised, open, multicentre study. Patients received 24 weeks' treatment with oral lamotrigine 100 mg (LTG 100, n = 115) or 200 mg (LTG 200, n = 111) or carbamazepine 600 mg (CBZ 600, n = 117). Efficacy measurements were comparable between the three treatment groups, although the higher lamotrigine dose was possibly most effective, with 60.4% completing seizure free compared with 51.3% (LTG 100) and 54.7% (CBZ 600). Both dosage regimens of lamotrigine were well tolerated. More patients on CBZ 600 reported adverse experiences, 66% versus 53% (LTG 100) and 58% (LTG 200), and of these a greater proportion were attributed to CBZ 600 treatment, 53% versus 23% (LTG 100) and 28% (LTG 200). Similarly, a greater proportion of the CBZ 600 group required a change in dose, 47% versus 20% (LTG 100) and 17% (LTG 200) or withdrew completely due to adverse experiences, 10.3% versus 4.3% (LTG 100) and 4.5% (LTG 200). The most common adverse experience leading to withdrawal was rash, with approximately double the proportion of reports occurring in patients on CBZ 600 (5.1%) compared with lamotrigine (1.7% on LTG 100 and 2.7% on LTG 200). Overall lamotrigine appeared equally effective but better tolerated compared with carbamazepine.

Adolescent↗

PubMed1996

Interictal SPECT of rCBF is of clinical utility in the preoperative evaluation of patients with partial epilepsy.

Fifty-eight patients with drug-resistant partial epilepsy were studied preoperatively by interictal rCBF measurements using 99mTc-HMPAO and a dedicated brain SPECT camera (Tomomatic 64). Follow-up of seizure outcome, using the "Engel score", was at least 3 years. The data were analyzed in a blinded set-up, first visually and subsequently quantitatively by an automatic regional analysis. By visual analysis 95% of the patients were considered abnormal in one part of the brain, of whom 27% were abnormal on CT, 45% on MRI and 98% on scalp EEG. Using a quantitative regional analysis subdividing each hemisphere into 17 larger regions, 85% of the patients had an abnormal rCBF compared to an age-matched control population of healthy volunteers (using the Wilcoxon 2-sample test with Bonferroni's correction). The average number of abnormal regions of interest was 4.7. The percentage of patients with abnormal SPECT-CBF or the total number of abnormal regions of interest (ROIs) per patient showed no correlation to duration of epilepsy or seizure load (number of seizures per year x epilepsy duration) or seizure type. Neither were the rCBF changes prognostic for the outcome as measured by the Engel score. In 20 patients ictal SPECT of rCBF was additionally performed. In 2 cases it added further information to the patient evaluation.

Adolescent↗

PubMed1996

The centromere-like parC locus of plasmid R1.

The parA partitioning system of plasmid R1 consists of three components: the cis-acting centromere-like parC locus, and two proteins, ParM and ParR. The parC locus contains two sets of five direct repeats (iterons) to which the ParR protein binds. The parA promoter is located in the core region between the two sets of iterons. Mini-R1 replicons carrying parC are stabilized by the simultaneous presence of ParM and ParR. The parC locus present on a co-resident plasmid leads to instability of the mini-R1 replicon (incompatibility). Here we present a genetic analysis of the stability and incompatibility phenotypes associated with parC. We show that all 10 iterons are required for maximum stabilization and incompatibility. Replacement of the core promoter region between the repeats by a foreign promoter region did not reduce stabilization. Thus, the only structural components in parC seem to be the two sets of iterons. The parA promoter, P parA, is repressed by ParR. We show that all 10 iterons are required for full repression of the promoter. The activity of the promoter was influenced by sequences located outside the core region. An A-rich region located upstream of the -35 element of PparA was found to increase promoter activity. The region encoding the parA mRNA leader region also strongly influenced the expression level of PparA- lacZ fusions. We show that this high expression (hex) element is a transcriptional antiterminator that prevents Rho-dependent termination.

Bacterial Proteins↗

PubMed1996

Double-blind, placebo-controlled trial of topiramate as add-on therapy in patients with refractory partial seizures.

In a double-blind, randomized, parallel-group trial, we compared topiramate (TPM) with placebo as add-on therapy in patients with refractory partial epilepsy. TPM was titrated either to the target dosage of 800 mg/ day [400 mg twice daily (b.i.d)] or to the maximal tolerated dose if lower. Twenty-eight (28) patients were randomized to each treatment group. In the intent-to-treat analysis, the net median percent reduction relative to placebo in average monthly seizure rate was 54% for patients in the TPM group (p < 0.001). None of the placebo-treated patients and 43% of the patients treated with TPM experienced > or = 50% reduction in seizures (p = 0.001), and 36% of patients assigned to TPM had a 75-100% reduction in seizures (p < 0.01). Secondarily generalized seizures were also significantly reduced in the TPM group (p = 0.044). The most common adverse events (AE) reported in the TPM group were fatigue, impaired concentration, weight loss, dizziness, and paresthesias. AE occurring either during the rapid titration of TPM or at high dosages led 21% of TPM-treated patients to withdraw from the study. Half of these occurred during the titration study period. No serious AE or clinically important changes in clinical laboratory measures were observed. The present study further establishes the favorable profile and good benefit/risk ratio of TPM in resistant partial epilepsy.

Adolescent↗

PubMed1996

Double-blind, placebo-controlled trial of topiramate (600 mg daily) for the treatment of refractory partial epilepsy.

PURPOSE: We wished to evaluate adjunctive therapy for partial-onset seizures with topiramate (TPM) for efficacy and safety in a double-blind, placebo-controlled, randomized, parallel-group study. METHODS: Sixty outpatients with epilepsy (47 men and 13 women, mean age 32.9 years) were studied. All had a documented history of partial-onset seizures with or without secondarily generalized seizures. After an 8-week baseline during which patients had at least one seizure per week, 30 patients each were randomized to TPM 300 mg twice daily (b.i.d.) or placebo for 12 weeks. RESULTS: TPM was significantly superior to placebo, as indicated by all efficacy assessments: greater median percent reduction from baseline in the average monthly seizure rate (46 vs. -12%, p = 0.004); greater number of treatment responders (patients with > or = 50% reduction in seizure rate) (47 vs. 10%, p = 0.001), and better investigator (p = 0.002) and patient (p = 0.010) global assessments of treatment. Among TPM-treated patients, the most commonly reported adverse events (AE) were headache, somnolence, fatigue, dizziness, and abnormal thinking. Most AE were mild or moderate in severity. CONCLUSIONS: The results of the present trial indicate that TPM 600 mg/day is effective in the treatment of refractory partial-onset seizures with or without secondarily generalized seizures.

Adolescent↗

PubMed1996

Epilepsy surgery.

Only 15% of patients with severe epilepsy with frequent partial seizures achieve any improvement in their seizure frequency by further drug treatment. As we know that epileptic seizures result in neuron loss with early development of mental deterioration, that the mortality rate of patients with epilepsy is increased and that an exact localization of the epileptogenic area which can be resected offers the possibility of curative treatment, we have a moral obligation to make this treatment available to people disabled with epilepsy. Surgery for mesial temporal sclerosis and lesional cortical partial epilepsy offers freedom from seizures in 70-80% of the patients, whereas non-lesional, cortical, partial epilepsy is more problematic, as only 30-40% of the patients will be seizure-free. Volumetric MRI, MR spectroscopy, SPECT and PET reduce the need for invasive monitoring in patients with temporal lobe epilepsy. Invasive recordings should be used when scalp-EEG, MRI, SPECT and PET cannot identify the epileptic focus; 50% of the patients who cannot be diagnosed by non-invasive recordings, can be diagnosed by invasive methods. When operated on 70% become seizure free, and a further 10% achieve a significant improvement. As age at surgery influences vocational outcome, surgical therapy should be considered in children. This will prevent their development into chronically ill patients, with all the known accompanying psychic handicaps this involves.

Brain↗