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Biomedical subjects

A Becker

Publications and source records attributed to A Becker.

At least 55 records · Page 3Linked to original sources

Efficacy of a vancomycin solution to prevent bacteremia associated with an indwelling central venous catheter in neutropenic and non-neutropenic cancer patients.

We evaluated the efficacy of a vancomycin solution in the prevention of bacteremia caused by vancomycin-sensitive organisms (VSO) in cancer patients with a tunneled central venous catheter (CVC). Eighty-three patients who had a single lumen CVC were randomized to use a heparin solution (25 U/ml) for daily catheter flush with (HepVan) or without (Hep) vancomycin, 25 mcg/ml. Febrile episodes were recorded, and central and peripheral blood cultures were drawn before beginning antibiotic therapy. Patients participated in follow-up to 16,677 catheter days (8,666 Hep and 8,011 HepVan), and 143 febrile episodes were recorded (82 Hep and 61 HepVan). Forty-four episodes of bacteremia occurred, 23 of them due to VSO (16 occurred in the Hep group and 7 in the HepVan group (P = 0.19). VSO bacteremia occurred in 14 neutropenic (absolute neutrophil count < 500 x 10(9)/l) episodes (7 Hep vs. 7 HepVan) and in 9 non-neutropenic episodes (9 Hep vs. O HepVan; P = 0.013). Vancomycin effectively prevented bacteremia by VSO in non-neutropenic patients, supporting the idea that intraluminal colonization of indwelling CVCs contributes to bacteremia only in these patients.

Adolescent

Diazepam--its effects on the development of pentylenetetrazol kindling, related learning impairments, and neuronal cell loss.

Epileptics frequently experience cognitive disturbances. It was speculated that seizure activity causes neuronal cell loss which might, in part, contribute to these disturbances. To shed light on this problem, the kindling (pentylenetetrazol) model of epilepsy was used. Diazepam (DZP) was intraperitoneally injected (0.5 or 2.5 mg kg-1) in the course of kindling development. Six weeks after kindling completion the animals were tested for their performance in a shuttle-box and finally, the brains were processed for histological examination. It was found that DZP suppressed the expression of motor seizures. Kindled animals showed a significantly diminished shuttle-box performance. This impairment was not ameliorated by DZP. Moreover, the learning performance in control animals pretreated with DZP was low suggesting long-lasting alterations due to DZP application. In kindled animals the number of neurones in the hippocampal CA1 region was significantly reduced and this effect was counteracted by the substance. The presented data suggest that seizure suppression and a reduction in neuronal cell loss must not automatically result in improved learning performance.

Analysis of Variance

Iodide or L-thyroxine to prevent recurrent goiter in an iodine-deficient area: prospective sonographic study.

In a randomized study, prevention of goiter recurrence with L-thyroxine was compared with pure iodide substitution after thyroid surgery for nodular goiter in an iodine-deficient area. Altogether 107 patients were followed up for 52 weeks after thyroid resection. The thyroid volume was determined sonographically. Free thyroxine, total thyroxine, thyrotropin, thyroglobulin, and antibodies to thyroglobulin and thyroid peroxidase were measured. The thyroid volume decreased slightly over the course of a year in the two therapy groups. There was no significant difference between the two groups. Recurrences were seen with both L-thyroxine medication and iodide substitution. The thyroglobulin levels fell significantly over the 52-week follow-up period in the iodide group. Antibody formation was not observed under iodine substitution. In an area of iodine deficiency, substitution with iodide is just as effective as medicating the patients with L-thyroxine for preventing recurrences.

Female

Kindling of the dorsal and the ventral hippocampus: effects on learning performance in rats.

The hippocampus represents a heterogeneous structure which has been associated with different functions. It has been suggested that it plays an important role in both learning and memory and epileptogenesis. Thus, it is not surprising that seizure activity generated in the hippocampal formation interferes with memory storage. Little is known about the functional differentiation between the dorsal (DH) and ventral hippocampus (VH). To study this functional differentiation, we kindled Wistar rats either in the DH or in the VH by electrical stimulation. Afterwards, learning performance of these rats was tested in three different models, i.e., response to change (short-term memory), shuttle box (two-way active avoidance), and Y-chamber (brightness discrimination reaction). It was found that VH-kindled rats reached higher seizure scores than DH-kindled rats, but there was no difference in seizure duration. Kindling induced in the VH significantly impaired shuttle box learning, whereas DH-kindled rats showed a dramatically worsened acquisition in the brightness discrimination task. Different anatomical projections probably account, in part, for these differences.

Animals

Effect of age on pentylenetetrazol-kindling and kindling-induced impairments of learning performance.

Epileptogenesis during ontogeny may not be linearly related to time. It is known that the behavioral manifestations of seizures are age-dependent, but more research is needed to clarify ontogenetic aspects of epilepsies and related alterations, including cognitive deficits. Kindling is an accepted animal model for the study of the convulsive component of epilepsy and its consequences on behavior. Recently, we demonstrated an impairment in acquisition of a conditioned reaction in young adult kindled rats, using pentylenetetrazol (PTZ) as the kindling stimulus. The present study was undertaken to investigate the dependence on age of alterations in the induction of PTZ kindling in rats. We started the kindling protocol in 4-, 6-, and 8-week- and 6-, 12-, 18-, and 24-month-old rats. The PTZ kindling showed an age-dependent decrease in expression of convulsions. The diminished kindling capacity was already seen in 6-month-old rats. In contrast, kindling-related impairment effects on cognitive functions increased with age. Thus, the correlation between learning impairment and occurrence of tonic-clonic seizures that we had demonstrated in 8-week-old rats was abolished in older rats. On the other hand, when the kindling procedure was started in 6-week-old rats, no impairment was found in fully kindled rats.

Aging

Differences between two substrains of AB mice in the opioid system.

Animals from two substrains of AB mice, i.e., ABH/Md and ABG/Md, differ in the occurrence of aggressive behavior. After maturation, male ABH mice regularly exhibited abnormal aggressive behavior making group-housing impossible. In contrast, ABG animals never showed such behavioral patterns. To elucidate the role of opioid mechanisms, we tested the reaction of these animals to morphine in the hot plate test. Moreover, specific DAMGO binding was measured. It was shown that mice from control groups differed significantly in reaction to the thermal stimulus. ABH mice had significantly longer reaction times. With increasing doses of morphine this difference disappeared, suggesting different levels of basal activity in endogenous opioid systems. This is underlined by significantly lower DAMGO binding in aggressive ABH mice. The results suggest that differences in endogenous opioid systems may account for differences in aggressiveness.

Aggression

Cleidocranial dysplasia: Part 2--Treatment protocol for the orthodontic and surgical modality.

The principles on which the present approach to the treatment of cleidocranial dysplasia are based were stated in part 1 of this article. Comparison was made with two other methods and the advantages of the present method were described in terms of (a) how this method is adapted to the clinical features of the condition, (b) when surgical intervention is appropriate, (c) how the dynamic appliance system may be adapted to the changing environment as more teeth erupt, and (d) the importance of rapidly bringing about the eruption of the anterior teeth. The practical aspects of the treatment are now described step-by-step with illustrations taken from the treatment of several different patients.

Adolescent

Cleidocranial dysplasia: Part 1--General principles of the orthodontic and surgical treatment modality.

Over several decades, occasional reports of dental treatment provided by an individual practitioner to patients suffering with cleidocranial dysplasia have appeared in the literature. In the past, the main treatment was prosthetic replacement. Orthodontic treatment has only recently been considered as a serious treatment option, with success being described in several aspects of this treatment modality, in published individual case reports. Given the rarity of the condition, guidelines for the treatment of cleidocranial dysplasia are difficult to find in the literature, because few practitioners have treated enough cases to be in a position to make such recommendations. Two different approaches have been proposed in the past and are discussed here. The relative advantages of a third approach are expounded in detail.

Child

Piracetam prevents pentylenetetrazol kindling-induced neuronal loss and learning deficits.

The effect of the nootropic drug piracetam (100 mg/kg) on kindled seizures, kindling-induced learning deficits, and histological alterations due to changes in central excitability was investigated in Wistar rats. The animals were kindled by repeated i.p. injections of an initially subconvulsive dose of pentylenetetrazol (PTZ). As a control, piracetam or physiological saline was given 60 minutes before PTZ. Twenty-four hours after completion of kindling the rats were tested in a shuttle-box paradigm. Seven days after the final kindling injection, the animals received a challenge dose of PTZ. Finally, the brains of the rats were processed for histological investigation. Pentylenetetrazol-kindled animals showed increasing seizure scores, and a learning deficit in the shuttle-box. Piracetam had no effect either on kindling development or on the reaction to a challenge dose of PTZ, but it protected the animals against the kindling-induced reduction of learning performance. The substance had no effect on learning performance in control animals. In distinct hippocampal structures, a neuronal cell loss was found in kindled rats. Interestingly, piracetam counteracted this damage efficaciously. The effects of piracetam are discussed in terms of its cytoprotective action. It is suggested that a coadministration of piracetam with clinically used antiepileptic drugs might be useful in antiepileptic therapy.

Animals

Influence of olfactory bulbectomy and subsequent imipramine treatment on 5-hydroxytryptaminergic presynapses in the rat frontal cortex: behavioural correlates.

1. Alterations of 5-hydroxytryptaminergic mechanisms are thought to play a special role in the pathogenesis of depression and antidepressant treatments are assumed to restore these changes. 2. We have used one of the most reliable models of depression, the olfactory bulbectomized rat to study the long term consequences of this manipulation and of subchronic imipramine treatment on two parameters of 5-hydroxytryptaminergic presynapses, 5-hydroxytryptamine (5-HT) transporter density and tryptophan hydroxylase apoenzyme concentration, in the frontal cortex as well as on active avoidance learning several weeks after bulbectomy. 3. The Bmax value of [3H]-paroxetine binding and the concentration of the 5-HT synthesizing enzyme were both significantly elevated in the frontal cortex of bulbectomized rats compared to sham-operated controls. 4. Imipramine treatment, either by daily injections or by subcutaneous implantation of slow release imipramine-containing polymers reduced the elevated tryptophan hydroxylase apoenzyme levels in the frontal cortex of bulbectomized, but not of sham-operated control rats and restored the deficient learning performance of bulbectomized rats. 5. Both effects were more pronounced after continuous drug administration by imipramine-releasing polymers compared to daily i.p. injections. 6. These findings indicate that bulbectomy leads to a compensatory 5-hydroxytryptaminergic hyperinnervation of the frontal cortex. Chronic antidepressant treatment seems to attenuate the increased output of the 5-hydroxytryptaminergic projections in the frontal cortex through the destabilization of the rate limiting enzyme of 5-HT synthesis of the 5-hydroxytryptaminergic nerve endings in this brain region.

Adrenergic Uptake Inhibitors

Mutations in the terminase genes of bacteriophage lambda that bypass the necessity for FI.

DNA maturation in bacteriophage lambda is the process by which the concatemeric precursor DNA is cleaved at sites called cos to generate mature lambda DNA molecules. These DNA molecules are then packaged into procapsids, the empty capsid precursors. The enzyme that catalyses these events is lambda DNA terminase. It is composed of two subunits, made of 181 and 641 amino acids, the products of genes Nu1 and A, respectively. The product of the FI gene (gpFI) stimulates the formation of an intermediate in capsid assembly called complex II, which contains a procapsid, terminase and DNA. The mechanism of stimulation remains unknown. It has been suggested that gpFI may also stimulate terminase-mediated cos cleavage, in the absence of procapsids, by increasing enzyme turnover. Mutants in FI fail to mature and package DNA but, in comparison with other capsid gene mutants, FI mutants are leaky. Second site mutants of FI phages, called 'fin' (for FI independence), bypass the necessity for gpFI. These mutants were originally localized to the region of Nu1 and A and are of two classes: finA includes those that induce the synthesis of fourfold more gene A product (gpA) than wild-type phages, and finB includes those that produce normal amounts of gpA. Whereas all finA mutants analysed map to Nu1, finB mutants have been found both in E and in Nu1. The existence of E mutants able to bypass the necessity for gpFI in vivo shows that gpE and gpFI interact, directly or indirectly. Here we have analysed and sequenced two finA mutants and one finB mutant. All of these map in Nu1. Of the two finA mutants, one corresponds to an Ala163Ser change and the other is a silent mutation. It is likely that the finA mutations alter mRNA conformation in a manner that results in an increase in the efficiency of A mRNA translation. The fourfold increase in gpA synthesis translates into a 10-fold increase in terminase activity. These results show that terminase overproduction is sufficient to bypass the necessity for gpFI and that such an overproduction can be achieved by changes in the efficiency of translation of A due to subtle changes in the sequence upstream of the gene. The finBcs103 mutation is a His-87-->Tyr change in Nu1. Therefore, an alternative way in which to bypass the requirement for gpFI involves an alteration in the structure of gpNu1. It is likely that the altered gpNu1 would increase cleavage and packaging efficiency directly or indirectly. We have determined that DNA cleavage in vivo does not occur in the absence of gpFI. Therefore it seems that gpFI somehow facilitates an otherwise latent capacity of terminase to autoactivate its nucleolytic activity.

Amino Acid Sequence

Response of rainbow trout (Oncorhynchus mykiss) to supplements of individual essential amino acids in a semipurified diet, including an estimate of the maintenance requirement for essential amino acids.

We studied the effects of increasing dietary concentrations of each of the following amino acids on growth, feed intake, feed conversion ratio and composition of gain in rainbow trout in six dose-response experiments: L-lysine, L-tryptophan, L-histidine, L-valine, L-leucine and L-isoleucine. Semipurified diets containing 20.1 MJ digestible energy/kg dry matter, with wheat gluten and crystalline amino acids as sole sources of amino acids, were fed to rainbow trout [initial mean body weight (BW) 40-51 g, depending on the amino acid studied]. In one series of 24 diets, lysine concentration ranged from 4.5 to 58.0 g/kg dry matter; in five further series of 12 diets each, concentrations ranged from (in g/kg dry matter): tryptophan, 1.3 to 5.6; histidine, 2.6 to 13.5; valine, 6.2 to 34.2; leucine, 10.0 to 42.0 and isoleucine, 5.0 to 15.3. Each diet was fed to a group of 20 fish for 53-64 d, depending on the amino acid studied. Dry matter intake, weight gain, feed conversion ratio, protein concentration of gain and total protein deposition followed exponential response functions. To achieve 95% of the maximum protein deposition, dietary concentrations of 27.7 g lysine, 2.0 g tryptophan, 5.8 g histidine, 15.7 g valine, 13.6 g leucine and 13.7 g isoleucine/kg dry matter were required. Maintenance requirements, estimated from exponential functions for protein deposition, were [in mg/(100 g BW.d)]: lysine, 1.93; tryptophan, 1.05; histidine, 1.07; valine, 2.92; leucine, 8.26 and isoleucine, 0.91. This corresponds to 4% of the requirement for protein deposition for lysine and isoleucine but 32% for leucine, with the other amino acids being intermediate. Therefore, different dietary amino acid requirement patterns were derived from protein deposition data depending on the chosen level of performance.

Amino Acids, Essential

Resistance to activated protein C and Legg-Perthes disease.

Thrombophilia may cause thrombotic venous occlusion in the femoral head, with venous hypertension and hypoxic bone death, leading to Legg-Perthes disease. Resistance to activated protein C, the most common thrombophilic trait, was measured in 64 children with Legg-Perthes disease. Genomic deoxyribonucleic acid was studied to delineate the CGA-->CAA substitution at position 1691 of the Factor V Leiden gene responsible for resistance to activated protein C. The activated protein C ratio was calculated by dividing clotting time obtained with activated protein C-calcium chloride by clotting time obtained with calcium chloride alone. Resistance to activated protein C, with a low activated protein C ratio (less than 2.19, the 5th percentile for 160 normal pediatric controls) was the most common coagulation defect, found in 23 of 64 children with Legg-Perthes disease versus 7 of 160 pediatric controls. Eight of 64 children with Legg-Perthes disease had a low activated protein C ratio and the mutant Factor V gene (7 heterozygotes, 1 homozygote) versus 1 of 101 normal pediatric controls. Two or 3 generation vertical and horizontal transmission of heterozygosity for the mutant Factor V gene was found in 4 of the 8 kindreds. Of 64 children with Legg-Perthes disease, only 14 (22%) had entirely normal coagulation measures. Resistance to activated protein C appears to be a pathogenetic cause of Legg-Perthes disease.

Blood Coagulation Disorders

Cardiovascular status after postural change in compensated cirrhosis: an argument for vasodilatory concept.

It seems that hypervolemia and vasodilatation coincide in compensated cirrhosis, but neither rank nor importance of these factors has been fully clarified in adaptive response to postural change. We studied, with gated equilibrium radionuclide angiography and thoracic electrical bioimpedance the hemodynamic status of 19 patients with compensated cirrhosis and 18 healthy subjects in upright and supine positions. In the upright position, the cirrhotic patients were hypotensive and had decreased peripheral vascular resistance despite increased cardiac output. The transition to the supine position was accompanied by a significant fall in the heart rate and an increase in the stroke volume in both controls (92 +/- 22 to 63 +/- 10 beats/min, and 38 +/- 9 to 62 +/- 19 ml/m2, respectively) and cirrhotic patients (101 +/- 20 to 79 +/- 13 beats/min, and 44 +/- 15 to 63 +/- 19 ml/m2, respectively). Besides, the diastolic arterial pressure fell in controls from 89 +/- 9 mmHg to 81 +/- 11 mmHg; p < 0.01, while it remained unchanged in cirrhotic patients (77 +/- 17 vs 82 +/- 13 mmHg). In the supine position, the cirrhotic patients presented tachycardia and left ventricular hyperkinesy (increased velocity of left ventricular filling and emptying). In conclusion, these results show that in compensated cirrhosis the decreased arterial tone and peripheral blood pooling are important factors of adaptive hemodynamic reaction to postural change.

Adult