Biomedical subjects
L Gram
Publications and source records attributed to L Gram.
[Antiepileptic drug therapy--current aspects].
Explore the source record for details and available documents.
[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.
Microbiological spoilage of fish and fish products.
Spoilage of fresh and lightly preserved fish products is caused by microbial action. This paper reviews the current knowledge in terms of the microbiology of fish and fish products with particular emphasis on identification of specific spoilage bacteria and the qualitative and quantitative biochemical indicators of spoilage. Shewanella putrefaciens and Pseudomonas spp. are the specific spoilage bacteria of iced fresh fish regardless of the origin of the fish. Modified atmosphere stored marine fish from temperate waters are spoiled by the CO2 resistant Photobacterium phosphoreum whereas Gram-positive bacteria are likely spoilers of CO2 packed fish from fresh or tropical waters. Fish products with high salt contents may spoil due to growth of halophilic bacteria (salted fish) or growth of anaerobic bacteria and yeasts (barrel salted fish). Whilst the spoilage of fresh and highly salted fish is well understood, much less is known about spoilage of lightly preserved fish products. It is concluded that the spoilage is probably caused by lactic acid bacteria, certain psychotrophic Enterobacteriaceae and/or Photobacterium phosphoreum. However, more work is needed in this area.
Vigabatrin withdrawal randomized study in children.
Controlled studies with new antiepileptic drugs are problematic and limited in children. Withdrawal randomization versus placebo in responders previously recognized in an open phase is a new design reported in adults which allows comparison to placebo without delaying the administration of the active compound. We applied such a design in refractory epileptic children in order to study vigabatrin (VGB) in children. Twenty-eight patients aged 1.5-18.5 years and having partially responded to VGB, prescribed in an open study for refractory epilepsy, were included. Patients were randomized to VGB (continued) or placebo (VGB blindy stopped in 3 weeks) for 2 months and seizure frequency was compared to the prerandomization period. More than 50% increase in seizure frequency induced drop-out. Fifteen patients received VGB, 13 others placebo, with the same clinical characteristics in both groups. The patients remaining in the study (primary efficacy endpoint) were more numerous on VGB (93%) than on placebo (46%) (P < 0.01) and seizure frequency (secondary endpoint) was lower on VGB than placebo (P < 0.05). The same results were observed in a subgroup of partial epilepsies. No status epilepticus was observed when withdrawing VGB and all patients returned to baseline status by reintroducing VGB. Such a randomized withdrawal design is therefore feasible in epileptic children. It provides the first VGB controlled study in this age range and demonstrates efficacy. It could be useful for future designs of drug trials in childhood epilepsy.
Shewanella alga bacteremia in two patients with lower leg ulcers.
The first Danish cases of Shewanella alga bacteremia in two patients with chronic lower leg ulcers are reported. Both patients were admitted to the hospital during the same month of a very warm summer and had been exposed to the same marine environment, thereby suggesting the same source of infection. Both patients survived; however, one of them had extensive myonecrosis, while the other patient had an uncomplicated course. The strains were initially believed to be Shewanella putrefaciens on the basis of key characteristics and results of the API 20NE identification system (bioMérieux, Marcy l'Etoile, France), but further genetic and physiological analyses identified them as Shewanella alga.
Interaction between fish spoilage bacteria Pseudomonas sp. and Shewanella putrefaciens in fish extracts and on fish tissue.
The interaction between fish spoilage bacteria, Pseudomonas sp. and Shewanella putrefaciens, was investigated using fish extract and fish tissue as model systems. Isolates of Pseudomonas that produced iron chelators, siderophores, inhibited growth of S. putrefaciens in a fish-extract-agar diffusion assay but no, or only weak, antagonistic activity was seen when the medium was supplemented with iron. Sterile-filtered supernatant fluid from a siderophore-producing Pseudomonas grown in fish extract was inhibitory to S. putrefaciens if the number of Psudomonas was above 10(8) cfu ml-1. In contrast, supernatant fluids from siderophore-negative Pseudomonas isolates did not inhibit growth of S. putrefaciens. The inhibitory effect was, except for one strain of Pseudomonas, not seen in supernatant fluids from iron-enriched cultures of Pseudomonas sp. Finally, siderophore-producing Pseudomonas sp. lowered the maximum cell level of S. putrefaciens 1-2 log units from 10(9) to 10(10) cfu g-1 when the strains were grown on fish muscle blocks at 0 degrees C but the growth rate of S. putrefaciens was not affected.
Pharmacokinetics of new antiepileptic drugs.
This article surveys the pharmacokinetic parameters for the new antiepileptic drugs (AEDs): felbamate, gabapentin, lamotrigine, oxcarbazepine, tiagabine, topiramate, and vigabatrin. Compared to the pharmacokinetics of standard AEDs, these new AEDs have progressed in terms of (a) longer half-lives, permitting once- or twice-daily dosing, (b) greatly reduced potential for drug interactions, thus increasing ease of treatment, and (c) general lack of hepatic enzyme induction, which facilitates polytherapy as well as other aspects of treatment.
Inhibitory Effects of Secondary Metabolites from the Red Alga Delisea pulchra on Swarming Motility of Proteus mirabilis.
Abnormal, uncoordinated swarming motility of the opportunistic human pathogen Proteus mirabilis was seen when a crude extract of the Australian red alga Delisea pulchra was added to the medium. This occurred at concentrations at which growth rate, swimming motility, cell elongation, polynucleation, and hyperflagellation were not affected. One halogenated furanone from D. pulchra inhibited swarming motility at concentrations that did not affect growth rate and swimming motility. Other structurally similar D. pulchra furanones had no effect on swarming, suggesting considerable specificity in the effects of furanones on swarming motility by P. mirabilis.
Changes in cell morphology of Listeria monocytogenes and Shewanella putrefaciens resulting from the action of protamine.
Protamine, which is an antibacterial basic peptide, was shown to alter the cell morphology of Listeria monocytogenes and Shewanella putrefaciens. Atomic force microscopy revealed that protamine smoothed the surface of cells, formed holes in the cell envelope, and caused fusion of S. putrefaciens cells. Immunoelectron microscopy of protamine-treated cells of both L. monocytogenes and S. putrefaciens showed great damage to the cell wall and condensation of the cytoplasm. Respiration of the cells was decreased due to treatment with sublethal concentrations of protamine, probably due to leakage or loss of cell envelope potential. It was concluded that protamine disrupted the outer surface structure and condensed the cytoplasm of sensitive cells and, in sublethal concentrations, altered membrane structures, thereby eliminating respiration.
Eukaryotic interference with homoserine lactone-mediated prokaryotic signalling.
Acylated homoserine lactones (AHLs) play a widespread role in intercellular communication among bacteria. The Australian macroalga Delisea pulchra produces secondary metabolites which have structural similarities to AHL molecules. We report here that these metabolites inhibited AHL-controlled processes in prokaryotes. Our results suggest that the interaction between higher organisms and their surface-associated bacteria may be mediated by interference with bacterial regulatory systems.
Drug treatment of epilepsy in the 1990s. Achievements and new developments.
There have been significant advances in the medical treatment of epilepsy in recent years. Improved formulations of several classical antiepileptic drugs (AEDs) have appeared, resulting in improved efficacy and decreased toxicity. A marked increase in the number of comparative investigations of AEDs has also made treatment choice somewhat simpler. Rational methods applied in the search for new AEDs have resulted in the introduction of several new AEDs. So far, evidence seems to indicate that progress has been made with regard to developing compounds not necessarily with superior efficacy but with simpler pharmacokinetics, avoiding enzyme induction as well as decreasing the number of interactions, and improving adverse effect profiles, in comparison to the previous generation of AEDs. A novel approach to the clinical testing of AEDs has made it possible to demonstrate unequivocal efficacy, as well as efficacy as monotherapy, very early in the development of novel compounds. Results of studies from developing countries seem to raise doubt with regard to the value of the old dogmatic principle that early treatment is important in terms of the long term prognosis for seizure control. Traditional ideas on the value of monotherapy have also been questioned on the basis of a novel concept of so-called 'rational polytherapy' which, however, still await scientific validation. On the basis of excellent epidemiological and large controlled clinical studies, our ideas of the necessary duration of AED treatment have become much more optimistic than before.
A practical guide to when (and how) to withdraw antiepileptic drugs in seizure-free patients.
Most patients with epilepsy will become seizure-free on antiepileptic drugs (AEDs) within a few years of diagnosis. More than 60% will remain so when the medication is withdrawn. After assessing the risks and benefits for the individual patient, withdrawal may be considered by the physician and informed patient or parent if the patient meets the following profile: normal neurological examination, normal IQ, normal electroencephalogram (EEG) prior to withdrawal, seizure-free for 2 to 5 years or longer, and no juvenile myoclonic epilepsy. AEDs can be safely withdrawn in the seizure-free patients over the course of 6 months, possibly even faster, especially in children.
Adverse effects of established and new antiepileptic drugs: an attempted comparison.
Seizures are but one aspect of the negative impact epilepsy has on patients' lives. Adverse effects of antiepileptic treatment may affect the patient's quality of life to an even greater extent than the occurrence of seizures. Adverse effects of antiepileptic drugs (AEDs) are common, and because the differences in efficacy are often marginal, adverse effects may be the most important factor in choosing the best AED for the patient. The search for more efficient and less toxic agents is constantly ongoing. Current evidence suggests that the new generation of AEDs is as efficient as the established AEDs and exhibits fewer adverse effects, but the scientific evidence from randomised clinical trials comparing established and new AEDs with each other is still pending.
Adjunctive treatment of partial seizures with tiagabine: a placebo-controlled trial.
Tiagabine is a new antiepileptic drug which acts by a novel mechanism, inhibiting the reuptake of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) into neurons and glia. A double-blind, placebo-controlled, crossover trial was undertaken, based upon a response-dependent design. Ninety-four patients with complex partial seizures with or without secondary generalised tonic-clonic seizures were recruited into an open screening phase and tiagabine was added to their existing drug therapy in doses titrated to reduce seizure frequency by > or = 25% or to the limit of tolerance. Forty-six responders were subsequently randomised to a double-blind crossover trial in which tiagabine was compared with placebo. Forty-two patients completed the trial. A significant reduction in the frequency of complex partial and secondary generalised tonic clonic seizures was seen. Twenty-six percent had a reduction of > or = 50% in the frequency of their complex partial seizures, and of the 27 patients who also had secondary generalised tonic clonic seizures, 63% experienced a reduction of > or = 50%. No interactions with baseline antiepileptic drugs were detected and no serious adverse reactions occurred. The commonest adverse events were tiredness, dizziness and headache. We conclude that tiagabine has promising antiepileptic effects. Further trials are underway.
Vigabatrin in childhood epilepsy: a 5-year follow-up study.
In an retrospective uncontrolled long-term study in 30 children with intractable epilepsy, it was found that treatment with vigabatrin resulted in a seizure reduction of more than 50% at 1-year follow-up in 40% of the children. The responders were all children with partial seizures. Side effects were mild and did not lead to discontinuation of the drug. Increased numbers of seizures were seen in three cases. A moderate weight increase was seen in 27% of the children. At 5-year follow-up 7 children (23%) still maintained a seizure reduction of more than 50%. Trials of monotherapy in three seizure-free patients were unsuccessful. No further side effects were observed. A study of evoked potentials in 12 children showed no alteration in latency and amplitudes of VEP following treatment with vigabatrin. Our results show that in children vigabatrin seems to have a stable effect even though a few children may experience a breakthrough of seizures. The presented results together with previous reports on MRI-scans seem to indicate that even in children with a still maturing CNS vigabatrin is a safe drug.
Antibacterial effect of protamine assayed by impedimetry.
Impedimetric measurements were used to assay the antibacterial effect of protamine. A good linear correlation between the impedance detection time and the initial cell counts was obtained (r = 0.99, n = 2). As basic peptides may cause clumping of cells, this correlation curve was used when estimating the cell number after protamine treatment, rather than colony counts. Protamine from salmon killed growing Gram-positive bacteria and significantly inhibited growth of Gram-negative bacteria in Tryptone Soy Broth (TSB) at 25 degrees C. In general Gram-positive bacteria were more sensitive to protamine than Gram-negative bacteria; the minimum inhibitory concentrations (MIC) determined for Gram-positive strains varied from 20 to 1000 micrograms ml-1 and for Gram-negative strains from 500 micrograms ml-1 to more than 4000 micrograms ml-1. The effect of protamine on non-growing Listeria monocytogenes Scott A suspended in buffer was not lethal as was the effect on growing cells; however, protamine (50-500 micrograms ml-1) killed the Gram-negative fish spoilage bacteria Shewanella putrefaciens when the live cells were suspended in buffer.
Epilepsy care: image of the future.
A number of factors have contributed to improvements in the care of epilepsy during the past decade, including the International League Against Epilepsy classifications, therapeutic antiepileptic drug (AED) monitoring and the concept of monotherapy, new AEDs with novel mechanisms of action, and new insights into etiology that suggest novel therapies. Pharmacologically "clean" AEDs acting on a single known mechanism will be an important element in the future care of patients with epilepsy. Augmentation of GABAergic inhibition is being successfully exploited by AEDs, and there remains much room for further pharmacologic innovation. The potential role of AEDs acting specifically on the GAT-1 or GAT-4 subgroup of gamma-aminobutyric acid transporters is a topic of current research. Specifically acting AEDs designed to have a single and known mode of action will permit true monotherapy, one AED with one target as opposed to one AED with several targets, and may open the way to rational polytherapy, i.e., designed use of one AED per mechanism in epilepsies with multifactorial causation. New research demonstrating a possible autoimmune basis for some forms of epilepsy illustrates the potential for novel nonpharmacologic approaches, and the role of prevention must also be emphasized. The image of the future is an optimistic one.