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Biomedical subjects

G Albrecht

Publications and source records attributed to G Albrecht.

At least 19 recordsLinked to original sources

Acquired neuromyotonia and peripheral neuropathy in a patient with Hodgkin's disease.

Acquired neuromyotonia is characterized by hyperexcitability of motor nerves resulting in continuous muscle fiber activity. It occurs most often as a paraneoplastic syndrome in patients with cancers of the immune system. Antibodies against voltage-gated potassium channels (VGKCs) have been detected in some patients. Peripheral neuropathy is sometimes present. We report on a patient with Hodgkin's lymphoma in complete remission who developed paresthesias followed by neuromyotonia with bulbar involvement. Peripheral sensorimotor neuropathy was diagnosed electrophysiologically and evidence of axonal degeneration and demyelination was detected by sural nerve biopsy. The patient's complaints, including dysarthria, improved after carbamazepine treatment.

Adult↗

The Child Behavior Checklist for group care workers: a study regarding the factor structure.

In this study we examined the factor structure of the Child Behavior Checklist (CBCL) filled out by group care workers. Group care workers' judgements were collected on 846 children and adolescents treated in various residential settings in The Netherlands. Using confirmatory factor analysis, we were able to show that the original CBCL factor model based on parental judgments of child behavior also fits for the judgments of group care workers. This means that the well known 8 narrow-band syndromes (Withdrawn, Somatic Complaints, etc.) as well as the 2 broad-band syndromes (Internalizing and Externalizing) can be used to interpret the CBCL scores of group care workers. This confirmation of the CBCL factor structure is a first step to add a group care worker version to the CBCL family. However, as a second step, normative data need to be gathered to further enhance the use of the CBCL for group care workers.

Adolescent↗

The association of menopause and physical functioning in women at midlife.

OBJECTIVES: To determine whether the characteristics of menstrual bleeding and the menopausal transition are associated with physical functioning in women age 40 to 55, after considering ethnicity, ability to pay for basics, body size, and age. DESIGN: Cross-sectional study. SETTING: Seven geographically dispersed community samples in the United States. PARTICIPANTS: The 14,427 respondents were Caucasians (46.9%), African Americans (28.7%), Chinese (4.0%), Japanese (5.3%), and Hispanics (12.6%) from the Study of Women's Health Across the Nation (SWAN) Cross-sectional Study, a study of the menopausal transition, including surgical menopause. MEASUREMENTS: The dependent variable was a three-category variable based on the physical functioning scale of the Medical Outcomes Study. Explanatory variables included menstrual and menopausal status. RESULTS: Eighty percent (80.8%) of women reported no limitation in physical functioning, whereas 10% of women had some limitation, and 9.2% of women indicated having substantial limitation. Women with substantial limitation in physical functioning had double the prevalence odds ratio (POR = 2.02; 95% confidence interval (CI) = 1.64-2.49) of having surgical menopause and 76% greater odds (POR = 1.76; 95% CI = 1.38-2.24)) of using hormones, compared with women with no limitation. Compared with those without limitation, women with substantial limitation in physical functioning had 56% greater odds (POR = 1.56; 95% CI = 1.23-1.97)) of being naturally postmenopausal and a 41% greater odds (POR = 1.41; 95% CI = 1.17-1.70) of being perimenopausal, relative to being premenopausal and after adjusting for other variables. CONCLUSION: Even at the relatively early age of 40 to 55, approximately 20% of women self-reported limitation in physical functioning. Surgical menopause and the use of hormones were more frequently observed in women with some and substantial physical limitation than in women with no limitation, even after adjusting for economic status, age, body mass index, and race/ethnicity.

Activities of Daily Living↗

An ARE-selective DNA minor groove binder from a combinatorial approach.

A synthetic combinatorial library of 10,000 components mostly containing aromatic amino acids was screened for inhibition of DNase I cleavage at two ARE sequences. Ten amino acid building blocks were used to generate the library in which the N and C terminal residues were fixed and the four central positions of the peptide ligands were varied. The DNase I footprinting assay led, after deconvolution through sublibrary synthesis, to the identification of CGL-6382 as an ARE-selective minor groove binder containing a N-terminal nicotinic acid motif adjacent to a N-methylimidazole unit and three N-methylpyrrole units coupled to a C-terminal argininamide residue. The optimized ligand CGL-6382 was found to recognize a 5'-GC(A/T)(A/T) motif within the two cloned androgen receptors responsive elements. The discovery of CGL-6382 as an ARE-selective ligand augurs well for the use of the DNase I footprinting methodology to identify sequence-specific DNA recognition ligands from large mixtures of small molecules.

Base Sequence↗

In vitro cloning of complex mixtures of DNA on microbeads: physical separation of differentially expressed cDNAs.

We describe a method for cloning nucleic acid molecules onto the surfaces of 5-micrometer microbeads rather than in biological hosts. A unique tag sequence is attached to each molecule, and the tagged library is amplified. Unique tagging of the molecules is achieved by sampling a small fraction (1%) of a very large repertoire of tag sequences. The resulting library is hybridized to microbeads that each carry approximately 10(6) strands complementary to one of the tags. About 10(5) copies of each molecule are collected on each microbead. Because such clones are segregated on microbeads, they can be operated on simultaneously and then assayed separately. To demonstrate the utility of this approach, we show how to label and extract microbeads bearing clones differentially expressed between two libraries by using a fluorescence-activated cell sorter (FACS). Because no prior information about the cloned molecules is required, this process is obviously useful where sequence databases are incomplete or nonexistent. More importantly, the process also permits the isolation of clones that are expressed only in given tissues or that are differentially expressed between normal and diseased states. Such clones then may be spotted on much more cost-effective, tissue- or disease-directed, low-density planar microarrays.

Cloning, Molecular↗

Mesigyna once-a-month combined injectable contraceptive: experience in Latin America.

A phase III clinical study was carried out among 534 fertile Latin American women to evaluate cycle control, side effects, and contraceptive efficacy of a once-a-month combined injectable, Mesigyna, consisting of 50 mg norethisterone enanthate and 5 mg estradiol valerate. The pregnancy rate at 1 year was 0 per 100 woman-years for a total experience of 4688 woman-months. The overall discontinuation rate at one year was 17.9%. Discontinuation rate for bleeding problems was 5.1%. The Colombian women had a significant increase (p <0.001) in bleeding problems compared to other countries. The discontinuation rate for amenorrhea was 1.1%. There were no significant differences between the groups regarding discontinuation for other medical or non-medical reasons. Mean weight gain after one year of use was 1.02 kg. Mesigyna is an appropiate once-a-month injectable contraceptive for Latin American women since it is highly effective and its perception of normal menstrual bleeding is of importance in the Latin American population.

Adolescent↗

Latin american experience with two low-dose oral contraceptives containing 30 microg ethinylestradiol/75 microg gestodene and 20 microg ethinylestradiol/150 microg desogestrel.

The objective of this study was to compare cycle control, efficacy and tolerance of an oral contraceptive containing 20 microg ethinylestradiol and 150 microg desogestrel with a preparation containing 30 microg ethinylestradiol combined with 75 microg gestodene. This study involved 342 women and 4104 cycles use in Argentina, Brazil, Chile, and Mexico. Contraceptive efficacy was good with both formulations. Two pregnancies occurred in the desogestrel group but were not due to method failure. With respect to cycle control, the incidence of intermenstrual bleeding was higher during the first 3 cycles in the desogestrel group; it was significant (p <0.01) during the first 3 days of the cycle for a normal or heavy bleeding only in the Mexican group. Amenorrhea was not reported for any group, but the incidence of dysmenorrhea was significantly higher (p <0.01) in the Brazilian desogestrel group (13.8%) and was significantly lower (p <0.01) in the Mexican gestodene group (8.5%). Adverse events were similar in all the countries with headache, breast tension, and nausea, the most frequently reported symptoms. The range of mean increase in body weight varied from 0.2 kg in the Argentine group to 2.6 kg in the Chilean group (95% confidence limit, +/- 2.51) in the gestodene group, and 0.2 kg in the Argentine group to 2.5 kg in Brazilian group (95% confidence limit, +/- 2.36) in the desogestrel group. Fifteen women discontinued because of headache, but there were no significant differences between the groups regarding discontinuation for this and other medical or non-medical reasons. Both oral contraceptive preparations are reliable and well tolerated, and both have favorable effects on control cycle.

Adolescent↗

[Skin manifestations of alcoholic liver damage].

Alcohol-induced diseases of the liver, such as fatty liver, hepatitis and cirrhosis with the potential development of hepato-cellular carcinoma can cause many effects on the skin. Even though they are not caused by excessive alcohol alone, but also by other diseases of the liver or other diseases of internal organs, an experienced person will be able to carry out specific diagnostic procedures. Skin symptoms due to liver diseases include 1. Vascular changes, such as spider nevi, teleangiectasias and palmar erythema. 2. Nail changes, particularly white nails. 3. Changes of the mucous membranes, i.e. glossy tongue. 4. Changes due to altered hormones, particularly gyneco-mastia, female distribution of hair and testicular atrophy and 5. Changes in the color of the skin like icterus and melanosis cutis. Rarely pruritus and other diseases of the skin are seen, such as porphyria cutanea tarda, which is often caused by an altered liver function. In the final stages of alcoholism, the neglect of personal hygiene particularly of the skin is evident (cutis vagantium). Since the exact mechanism of the skin symptoms remains obscure, it is difficult to evaluate the significance. Most often they do not correlate with the severity of the liver disease.

Alcohol-Related Disorders↗

Gene expression analysis by massively parallel signature sequencing (MPSS) on microbead arrays.

We describe a novel sequencing approach that combines non-gel-based signature sequencing with in vitro cloning of millions of templates on separate 5 microm diameter microbeads. After constructing a microbead library of DNA templates by in vitro cloning, we assembled a planar array of a million template-containing microbeads in a flow cell at a density greater than 3x10(6) microbeads/cm2. Sequences of the free ends of the cloned templates on each microbead were then simultaneously analyzed using a fluorescence-based signature sequencing method that does not require DNA fragment separation. Signature sequences of 16-20 bases were obtained by repeated cycles of enzymatic cleavage with a type IIs restriction endonuclease, adaptor ligation, and sequence interrogation by encoded hybridization probes. The approach was validated by sequencing over 269,000 signatures from two cDNA libraries constructed from a fully sequenced strain of Saccharomyces cerevisiae, and by measuring gene expression levels in the human cell line THP-1. The approach provides an unprecedented depth of analysis permitting application of powerful statistical techniques for discovery of functional relationships among genes, whether known or unknown beforehand, or whether expressed at high or very low levels.

Cell Line↗

[Thrombosis of the basilar artery--a rare differential sudden deafness diagnosis and vestibular failure].

BACKGROUND: Occlusion of basilar artery is a rare and life-threatening event. A quick and safe diagnosis and initiation of adequate therapy are decisive. For the ENT-specialist it is important to know that this thrombosis, which runs a lethal course in many cases, can develop with a disturbance of hearing and/or vestibular function as initial symptoms. PATIENTS: Reported are four cases of thrombosis of the basilar or vertebral artery. Two out of four patients contacted the ENT emergency unit because of symptoms of acute vestibular neuritis, one patient was previously diagnosed with sudden deafness by a local ENT-specialist, one patient was treated for hypertension induced epistaxis in one of our wards. Only one patient initially presented additional neurological symptoms, causing suspicion for a brainstem lesion as well. However these symptoms were only noticed on close examination. By immediate anticoagulation therapy (with Heparin) progress of thrombosis could be avoided. The patient showed a complete recovery and was free of any symptoms two years after thrombosis. Two of the other two patients developed a delayed onset of neurological symptoms next to the initial symptoms of vestibular and cochlear affection (within 24 hours), therefore diagnosis of thrombosis was late and despite of immediate anticoagulation therapy (with Heparin) both patients died. The one patient treated for hypertension induced epistaxis developed only discrete symptoms of basilar artery thrombosis, nevertheless he was diagnosed and treated immediately. He made a complete recovery and was dismissed two weeks later. CONCLUSIONS: It is therefore necessary to carefully control and sometimes correct diagnosis in cases of sudden deafness and acute vestibular neuritis. Especially additional neurological symptoms indicate the necessity of a MRI-angiogram or CT-(angiography)scan to exclude thrombosis of the basilar artery.

Adult↗

Measuring work stress among Dutch dentists.

Individual differences among dentists determine to a large degree what is experienced as work stress, but assessment of specific areas is necessary to be able to act preventively. The aim of this study was to develop an instrument to be used to monitor the experience of work stress in detail, to measure its levels, and to relate those levels to job (dis-) satisfaction. A questionnaire was developed, the Dentists' Experienced Work Stress Scale (DEWSS), covering widespread aspects of dental work, which was completed by 709 dentists, forming a highly representative sample of Dutch general dental practitioners. Factorial, correlational, and reliability analyses were conducted, after which seven areas of stress emerged: Work Pressure, Financial Aspects, Patient Contacts, Work Contents, Career Aspects, Team Aspects, and Professional and Private Life. Of these, Patient Contacts and Work Contents showed highest mean scores, as did the specific items: 'defaulters', 'governmental instructions', and 'unreasonable or demanding patients'. A strong inverse relationship was found between work stress, in particular lack of career perspective, and job satisfaction. The questionnaire is a valuable instrument to monitor pressure at work as felt by Dutch general dental practitioners. Patient contacts, work pressure, and career perspective clearly need preventive attention in the Dutch situation.

Cohort Studies↗

[Multilocular vegetating pyoderma gangrenosum].

Vegetative pyoderma gangrenosum is a nonaggressive, chronic, superficial variant of pyoderma gangrenosum. Unlike classic ulcerative pyoderma gangrenosum, the lesions are less deep and not painful, and the borders are not undermined. The base of ulcers usually shows granulation tissue. The histopathologic findings are characterized by superficial granulomas. Cultures for fungal or bacterial infections normally are negative. Vegetative pyoderma gangrenosum is seldom associated with systemic diseases and often responds to simple modes of therapy. Our patient had a 10 years history of superficial ulcers on face, trunk and upper arms, whose general health was not impaired. A broad diagnostical evaluation showed no systemic diseases. The histologic pattern demonstrated a granulomatous dermatitis. After exclusion of other causes, we believe the patient has the vegetative form of pyoderma gangraenosum. There was no improvement with local treatment. Only systemic therapy with corticosteroids and later on cyclosporine led to healing.

Adult↗

Sucrose synthase activity does not restrict glycolysis in roots of transgenic potato plants under hypoxic conditions

The effect of hypoxia on root development and carbon metabolism was studied using potato (Solanum tuberosum L.) plants as a model system. Hypoxia led to a cessation of root elongation, and finally to the death of meristematic cells. These changes were accompanied by a 4- to 5-fold accumulation of hexoses, suggesting that insufficient carbohydrate supply was not the cause of cell death. In addition, prolonged hypoxia (96 h) resulted in a 50% increase in activity of most glycolytic enzymes studied and the accumulation of glycerate-3-phosphate and phosphoenolpyruvate. This indicates that endproduct utilisation may restrict metabolic flux through glycolysis. As expected, the activities of alcohol dehydrogenase (EC 1.1.1.1) and pyruvate decarboxylase (EC 4.1.1.17) increased during hypoxia. Apart from the enzymes of ethanolic fermentation the activity of sucrose synthase (SuSy; EC 2.4.1.13) was enhanced. To investigate the in-vivo significance of this increase, transgenic plants with reduced SuSy activity were analysed. Compared to untransformed controls, transgenic plants showed a reduced ability to resume growth after re-aeration, emphasising the crucial role of SuSy in the toleration of hypoxia. Surprisingly, analysis of glycolytic intermediates in root extracts from SuSy antisense plants revealed no change as compared to wildtype plants. Therefore, limitation of glycolysis is most likely not responsible for the observed decreased ability for recovery after prolonged oxygen starvation. We assume that the function of SuSy during hypoxia might be to channel excess carbohydrates into cell wall polymers for later consumption rather than fuelling glycolysis.

Journal Article↗

Intermittent short courses of cyclosporin (Neoral(R)) for psoriasis unresponsive to topical therapy: a 1-year multicentre, randomized study. The PISCES Study Group.

We performed a 1-year study to determine whether intermittent short courses of the microemulsion formulation of cyclosporin (Neoral) could effectively control plaque psoriasis and whether tapering or abrupt cessation of cyclosporin therapy would influence time to relapse. Four hundred patients with plaque psoriasis were included in this open, multicentre, randomized study. All patients commenced cyclosporin at a dose of 2.5 mg/kg daily. Cyclosporin dosage could be increased to a maximum of 5 mg/kg daily. Treatment was continued until clearance of psoriasis or for a maximum of 12 weeks. Patients were then randomly assigned either to stop cyclosporin abruptly or to have the dose reduced by 1 mg/kg daily each week until cessation. On relapse, patients were given another course of cyclosporin. Patients were followed for at least 1 year, during which they could receive as many treatment courses as necessary. The number of patients who required one, two, three and four treatment courses was 400, 259, 117 and 26, respectively. The median time to relapse after the end of the first treatment period was 109 days in the group of patients randomized to stop cyclosporin abruptly and 113 days in patients randomized to taper off cyclosporin (P = 0.038). More than 30% of patients had not relapsed 6 months after having stopped treatment. After each treatment course, the Kaplan-Meier probability of achieving 75% or more reduction in disease area by day 84 of treatment was 83%, 76%, 73% and 66%, respectively. Mean serum creatinine concentration and blood pressure did not show any clinically significant changes over time. Our results show that intermittent short-course therapy with Neoral, when used in conjunction with topical therapy, is well tolerated and provides effective control of plaque psoriasis for 1 year. Tapering off cyclosporin on treatment cessation induces a slight delay in psoriasis relapse.

Adolescent↗

Professional burnout among Dutch dentists.

UNLABELLED: Professional burnout, a long-term consequence of occupational stress, is considered to be a factor that explains a substantial proportion of incapacity for work. Burnout is defined as emotional exhaustion, depersonalization, and diminished personal accomplishment. AIMS: To investigate levels of burnout among Dutch practising dentists, to compare dentists' scores with norm scores, and to determine the percentage of dentists "at risk". METHODS: The instrument used was the Dutch version of the Maslach Burnout Inventory (MBI-NL), a 20-item modified version of the original MBI. A highly representative group of Dutch dentists participated (n = 709, 75% response rate). RESULTS: Mean levels (and standard deviations) of burnout were: emotional exhaustion 13.7 (8.6); depersonalization 5.9 (3.9); personal accomplishment 30.8 (5.9). Dentists had more favourable means compared with standard scores, although in the 95th percentile dentists showed more emotional exhaustion than standards indicate. While no overall sex differences were found, male middle-aged dentists tended to show more burnout. Of the working Dutch dentists, 21% had a certain risk, 13% had high overall levels of burnout, and 2.5% were highly burned out. CONCLUSION: It is concluded that Dutch dentists have relatively favourable mean levels of burnout, but those who are exhausted are extremely exhausted. The male dentist in his forties appears to be most vulnerable to burnout.

Adult↗

TAR-RNA binding by HIV-1 Tat protein is selectively inhibited by its L-enantiomer.

An oligoribonucleotide, corresponding to the Tat-interactive top half of the HIV-1 TAR RNA stem-loop, was synthesized in both the natural D- and the enantiomeric L-configurations. The affinity of Tat for the two RNAs, assessed by competition binding experiments, was found to be identical and is reduced 10-fold for both, upon replacement of the critical bulge residue U23 with cytidine. It is suggested that this interaction of the flexible Tat protein depends strongly upon the tertiary structure of a binding pocket within TAR, but not upon its handedness, and may be described by a 'hand-in-mitten' model.

Binding, Competitive↗

Monitoring the Gcn4 protein-mediated response in the yeast Saccharomyces cerevisiae.

In Saccharomyces cerevisiae the GCN4 gene encodes the transcriptional activator of the "general control" system of amino acid bioynthesis, a network of at least 12 different biosynthetic pathways. We characterized the consequences of the general control response upon the signal "amino acid starvation" induced by the histidine analogue 3-aminotriazole with respect to Gcn4p levels in more detail. Therefore, we established test systems to monitor the time course of different parameters, including GCN4 mRNA, Gcn4 protein, Gcn4p DNA binding activity, as well as Gcn4p transactivation ability. We observed a biphasic response of Gcn4p activity in the cell. At first, translation of GCN4 mRNA is induced within 20 min after switch to starvation conditions. However, an additional increase in GCN4 transcript steady state level was observed, leading to an additional second phase of GCN4 expression after 3-4 h of starvation. The DNA binding activity of Gcn4p, as well as the ability to activate transcription of target genes, correlate with the amount of Gcn4 protein in the cell, suggesting that under the tested conditions there is no additional regulation of DNA binding or transactivation ability of Gcn4p, respectively.

Amitrole↗

Re-Aeration following Hypoxia or Anoxia Leads to Activation of the Antioxidative Defense System in Roots of Wheat Seedlings

The response of the ascorbate-glutathione cycle was investigated in roots of young wheat (Triticum aestivum L.) seedlings that were deprived of oxygen either by subjecting them to root hypoxia or to entire plant anoxia and then re-aerated. Although higher total levels of ascorbate and glutathione were observed under hypoxia, only the total amount of ascorbate was increased under anoxia. Under both treatments a significant increase in the reduced form of ascorbate and glutathione was found, resulting in increased reduction states. Upon the onset of re-aeration the ratios started to decline rapidly, indicating oxidative stress. Hypoxia caused higher activity of ascorbate peroxidase, whereas activities of monodehydroascorbate reductase, dehydroascorbate reductase, and glutathione reductase were diminished or only slightly influenced. Under anoxia, activities of ascorbate peroxidase and glutathione reductase decreased significantly to 39 and 62%, respectively. However, after re-aeration of hypoxically or anoxically pretreated roots, activity of enzymes approached the control levels. This corresponds with the restoration of the high reduction state of ascorbate and glutathione within 16 to 96 h of re-aeration, depending on the previous duration of anoxia. Apparently, anoxia followed by re-aeration more severely impairs entire plant metabolism compared with hypoxia, thus leading to decreased viability.

Journal Article↗