[Post-pharyngitis sepsis caused by Fusobacterium necrophorum: Lemierre's syndrome].
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Child, Preschool↗
Biomedical subjects
R de Groot
Publications and source records attributed to R de Groot.
Homologous RNA recombination allows efficient introduction of site-specific mutations into the genome of coronavirus MHV-A59 via synthetic co-replicating RNAs.
We describe a novel strategy to site-specifically mutagenize the genome of an RNA virus by exploiting homologous RNA recombination between synthetic defective interfering (DI) RNA and the viral RNA. Marker mutations introduced in the DI RNA were replaced by the wild-type residues during replication. More importantly, however, these genetic markers were introduced into the viral genome: even in the absence of positive selection MHV recombinants could be isolated. This finding provides new prospects for the study of coronavirus replication using recombinant DNA techniques. As a first application, we describe the rescue of the temperature sensitive mutant MHV Albany-4 using DI-directed mutagenesis. Possibilities and limitations of this strategy are discussed.
Base Sequence↗
Blind, deaf and mute after a status epilepticus caused by hyperpyrexia from shigellosis--a case report with a four-year follow-up.
A nearly four-year-old boy awoke blind, deaf and mute from a coma of five days duration after a status epilepticus caused by hyperpyrexia from shigellosis. The authors give a detailed report of the recovery. Visual and auditory functions recovered within six months after the onset but expressive language difficulties remained. Following a discussion of the underlying mechanisms producing the cerebral damage, the hypothesis of a type of "disconnection syndrome" is put forward to explain the persisting language deficit.
Age of Onset↗
Small-cell undifferentiated (neuroendocrine) carcinoma of the cecum in a child with common variable immunodeficiency.
PURPOSE: Patients with primary or secondary immunodeficiencies are known to be at increased risk for the development of malignancies, predominantly of lymphoreticular origin. PATIENTS AND METHODS: We here describe a patient with infant-onset hypogammaglobulinemia due to a common variable immunodeficiency. At the age of 16 a small-cell undifferentiated (neuroendocrine) carcinoma of the cecum (SCUNC) was diagnosed. RESULTS: Neurohormonal analysis showed normal values. CONCLUSIONS: To our knowledge this is the first report in childhood of SCUNC of the gastrointestinal tract, which has also previously not been associated with primary immunodeficiency.
Carcinoma, Small Cell↗
Mechanical performance of a dental composite: probabilistic failure prediction.
In clinical situations, the mechanical performances of dental structures--for example, composite restorations--depend on many factors. Most of them have a probabilistic character. Because composites are brittle materials, their strength should also be considered as a probabilistic quantity. For successful prediction of mechanical failure of structures consisting of these materials, a probabilistic approach is indispensable, and a suitable definition of equivalent stress must be introduced. An equivalent stress facilitates the transfer of strength data of laboratory specimens to situations where the stress state is much more complicated. The tensile and compressive strengths of composites differ considerably. Of two equivalent stress definitions that potentially describe this experimental fact (the Drücker-Prager and the Modified von Mises equivalent stress), the predictive capacity was investigated for a microfine composite. In a probabilistic approach to failure, use of the Drücker-Prager equivalent stress appeared to be superior, because the average failure load of notched beams was predicted with an error smaller than 8%.
Bisphenol A-Glycidyl Methacrylate↗
Trimethoprim resistance in Haemophilus influenzae is due to altered dihydrofolate reductase(s).
We characterized a highly purified preparation of the chromosomally encoded dihydrofolate reductase (DHFR) from a trimethoprim-susceptible (Tmp8; strain MAP) and two trimethoprim-resistant (TmpR) strains (MAP/47 and MAP/42) of Haemophilus influenzae. The enzymes were purified between 650- and 3000-fold by gel-filtration and dye-ligand chromatography. The apparent molecular mass of the three proteins was 18400 Da by PAGE under denaturing and nondenaturing conditions. Total enzyme activity was greater in all fractions from the TmpR strains compared with the Tmp8 isolate. The three enzymes had a similar Km for dihydrofolate (7, 9 and 5 microM) and NADPH (2, 5 and 6 microM). However, the Tmp IC50 (the concentration necessary for 50% inhibition of DHFR activity) for the Tmp8 strain MAP was 0.001 microM, whereas DHFR from the TmpR strains MAP/47 and MAP/42 had values of 0.1 microM and 0.3 microM respectively. The methotrexate IC50 of the MAP/42 DHFR was 0.06 microM in comparison with the enzyme from MAP (0.008 microM) and MAP/47 (0.007 microM). Isoelectric focusing indicated that the DHFR from MAP/42 had a different isoelectric point (pI 7.6) compared with the enzymes from MAP and MAP/47 (pI 7.3). Peptide mapping after digestion with trypsin revealed one major peptide fragment (7.9 kDa) in the DHFR of MAP and MAP/47 and three major tryptic fragments (7.9, 9.6 and 12.5 kDa) in DHFR from MAP/42. We conclude that trimethoprim resistance in H. influenzae results from overproduction of structurally altered DHFR(s).
Chromatography, Gel↗
[Haemophilus influenzae type b infections in children].
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Anti-Bacterial Agents↗
[Pneumocystis carinii pneumonia in patients with a severe combined immunodeficiency].
We describe three patients with Pneumocystis carinii pneumonia as the initial presentation of severe combined immunodeficiency disease. The pneumonia in the first patient was treated successfully with trimethoprim/sulphamethoxazole (Tmp/Smz). The second patient died despite therapy with Tmp/Smz and pentamidine. The third patient failed to respond to therapy with Tmp/Smz and pentamidine. He was subsequently treated with trimetrexate and leucovorin. Treatment with the new folic acid antagonist trimetrexate resulted in complete recovery. The case histories of these children serve to illustrate the clinical symptoms and new therapeutic modalities of P. carinii pneumonia in patients with immunodeficiency disease.
Humans↗
Antibiotic resistance in Haemophilus influenzae: mechanisms, clinical importance and consequences for therapy.
Invasive and non-invasive infections caused by Haemophilus influenzae are frequently diagnosed in children below the age of 5 years. The treatment of choice for these infections was ampicillin. However, since the early 1970s the increasing prevalence of resistance to ampicillin and other antibiotics has necessitated major changes in antibiotic therapy. This article summarizes some of the important clinical features of diseases caused by H. influenzae. The epidemiology, the problems with in vitro susceptibility testing and the mechanisms of resistance to major antibiotics are reviewed. The consequences of antibiotic resistance for the treatment of diseases caused by H. influenzae are discussed.
Aged↗
Positive regulation of jun/AP-1 by E1A.
Proteins encoded by the adenovirus E1A oncogene are capable of positive and negative transcriptional regulation of both viral and cellular genes. E1A regulatory function is commonly thought to involve modifications of specific cellular factors that interact with responsive promoters. In this report we present evidence that E1A induces the activity of the jun/AP-1 transcription factor in three different cell types: P19, JEG-3, and HeLa. AP-1 binds to 12-O-tetradecanoylphorbol-13-acetate (TPA)-responsive elements (TREs); therefore, E1A might modulate a specific signal transduction pathway normally induced by activation of the protein kinase C. Binding of jun/AP-1 to a TRE is induced in all cell types studied when E1A is expressed. We observe that the expression of endogenous c-jun and jun B genes is induced by E1A, which directly transactivates the promoters of c-fos, c-jun, and jun B. Similar inducibility is obtained by treatment with retinoic acid and differentiation of P19-embryonal carcinoma cells. The E1A 13S product transactivates TRE sequences and cooperates with c-jun in the transcriptional stimulation. The 12S E1A product does not activate a TRE sequence, but cotransfection with c-jun circumvents this lack of stimulation. Coexpression of c-fos and E1A 12S, however, blocks the transactivation by c-jun, suggesting an important role for fos in determining the dominance of the 12S or 13S protein.
Adenovirus Early Proteins↗
Probenecid pharmacokinetics in cystic fibrosis.
Probenecid pharmacokinetics were studied in 5 cystic fibrosis (CF) subjects and 5 control subjects at oral dosages of 5, 15, and 30 mg/kg. Serum and urine samples were collected for 8 h after administration and assayed by reverse phase high performance liquid chromatography. Pharmacokinetic parameters were estimated by model-independent methods. All parameters were compared by 2-tailed analysis of variance with two major groupings: patient and dose. Both CF subjects and controls demonstrated dose-dependent kinetics, i.e., decreased elimination constant and decreased total body clearance with increasing dosage. The volume of distribution and time to peak were the only parameters that were not significantly dose dependent. At all dosages studied, we found no significant difference in total body clearance by CF subjects. Urinary recovery in an 8-hour period was not significantly different between CF subjects and controls nor was the percentage of dose recovered in the urine at each dosage level. Time to peak concentration varied widely between 0.5 and 4 h in both CF subjects and controls. We conclude, that CF patients have normal probenecid clearance, and that the standard dose for a CF patient is sufficient to attain a serum area under the curve equivalent to that of controls.
Administration, Oral↗
Ichthyosis, exocrine pancreatic insufficiency, impaired neutrophil chemotaxis, growth retardation, and metaphyseal dysplasia (Shwachman syndrome). Report of a case with extensive skin lesions (clinical, histological, and ultrastructural findings)
The Shwachman syndrome comprises exocrine pancreatic insufficiency, growth retardation, and bone marrow hypoplasia resulting in neutropenia. Clinical, morphological, and ultrastructural studies, as well as hair analysis, were performed in a patient with Shwachman's syndrome and severe ichthyosis. Clinical findings were lamellar ichthyosiform desquamation on the extremities. The hair was scanty and short on the scalp, in the eyelashes, and in the eyebrows. The nails were hyperkeratotic. Morphologic findings were slight, regular acanthosis and severe diffuse hyperkeratosis with variable parakeratosis. The granular layer was thickened. The papillary dermis showed very slight perivascular lymphocyte infiltration. The most prominent ultrastructural finding was the presence of solitary or multiple droplets of varying size in the cytoplasm of the keratinocytes. Hair analysis revealed no abnormalities; the cystine concentration in hair specimens was normal.
Bone Diseases, Developmental↗
Cystic fibrosis, pathophysiological and clinical aspects.
Cystic fibrosis is a lethal, hereditary, until recently little understood disease, which leads to progressive functional disturbances in various organs, including the lungs, liver and pancreas. Knowledge of the genetic and cellular abnormalities is rapidly progressing, but therapy is still symptomatic and based on insufficiently controlled and short-term studies. At present the therapeutic approach aims to combat respiratory infections by optimal antibiotic therapy, combined with techniques to promote sputum evacuation. Additional measures attempt to optimise both nutritional state and physical condition. Median survival has improved from approximately 1 year to about 25 years during the past 3 decades. This article summarises present information on disease mechanisms and treatment.
Cystic Fibrosis↗
Pharmacokinetics of ticarcillin in patients with cystic fibrosis: a controlled prospective study.
We compared the pharmacokinetics of ticarcillin at a dose of 120 mg/kg in 11 patients with cystic fibrosis to 11 control subjects matched for age and sex. The mean elimination half-life of ticarcillin in serum was 70.8 minutes in the control subjects and 53.1 minutes in the patients with cystic fibrosis. The total body clearance of ticarcillin was significantly higher in cystic fibrosis patients (65.6 +/- 22.0 versus 46.2 +/- 10.9 ml/min/m2 in control subjects; p = 0.017). The nonrenal clearance of ticarcillin was also significantly higher in patients with cystic fibrosis (24.8 +/- 11.1 versus 13.3 +/- 6.0 ml/min/m2 for the control group; p = 0.006). There was no significant difference in volume of distribution between the two groups. We concluded that the shorter elimination half-life and the higher total body clearance of ticarcillin in patients with cystic fibrosis are a result of an increase in both renal and nonrenal elimination.
Adolescent↗
Fracture-mechanics parameters of the composite-enamel bond.
In a previous study, the critical values of the opening mode stress intensity factor (K1), its equivalent, the strain energy-release rate (G1), and the J integral (J1) (in the elastic case being equal to that of G1) were determined for resin composite. In this study, the strength of the composite-tooth interface was investigated. The critical values of K1 and J1 were measured with single-edge notched-bend (SENB) specimens of resin composite bonded to enamel, with the notch at midspan at the bonded interface. Due to enamel's anisotropy, the values of Klc and Jlc to be used in a fracture-mechanics application for failure prediction of a structure depend on the enamel prism orientation relative to the adhesive interface. Where interfacial failure is to be expected, the following values for Jlc and Klc can be used: Silux, Jlc = 145 +/- 35 Jm-2 and Klc = 0.84 +/- 0.16 MNm-3/2; P-30, Jlc = 163 +/- 13 Jm-2 and Klc = 1.02 +/- 0.07 MNm-3/2. Where enamel failure is expected or where the failure mode cannot be predicted, the following values can be applied: Silux, Jlc = 89 +/- 15 Jm-2 and Klc = 0.84 +/- 0.16 MNm-3/2; P-30, Jlc = 89 +/- 15 Jm-2 and Klc = 0.75 +/- 0.10 MNm-3/2.
Composite Resins↗
[Congenital cytomegalovirus infection].
Until recently, prevention and treatment of congenital cytomegalovirus infection was not possible. However, several studies on the epidemiology of congenital CMV infection and the development of vaccines, diagnostic tests and antiviral drugs such as ganciclovir may improve the perspectives for patients with congenital CMV disease. In this article we will discuss several of those developments that may offer new approaches for prevention and treatment of congenital CMV disease.
Cytomegalovirus↗
[Bacterial meningitis in young children. Current viewpoints in pathogenesis, treatment and prevention].
Bacterial meningitis is frequently diagnosed in children below the age of five years. Recently our understanding of the pathophysiology of meningitis has been enhanced by several innovative studies. In addition the development and future application of conjugate vaccines against H. influenzae, N. meningitidis, and S. pneumoniae will result in a substantial reduction of morbidity and mortality in patients with meningitis caused by these microorganisms. This review will discuss the current status on the epidemiology, pathophysiology, prevention and treatment of meningitis.
Adrenal Cortex Hormones↗
Use of antibiotics in neonates weighing less than 1200 g.
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Anti-Bacterial Agents↗