Cascading towards vascular disorder gene therapy.
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Biomedical subjects
Publications and source records attributed to S Ludwig.
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As the number of children with central venous catheters cared for at home continues to escalate, the physician is increasingly confronted with a wide variety of devices in the emergency setting. The most common presenting complaints are fever (infection), occlusion (thrombus), breakage, and dislodgement. Familiarity with the basic characteristics of these devices and their variations, as well as the approaches to specific complaints, will lead to prompt, efficient, and definitive emergency care for these patients.
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Children account for 30% of visits to emergency departments, and approximately 5% of these children have serious illness requiring immediate intervention. Over the past decades, as medical knowledge and application have eradicated many illness and rendered others curable, trauma has emerged as the leading cause of morbidity and mortality after the first year of life. However, all children remain vulnerable to infection and its consequences in the first year and beyond the first year. Additionally, over this time span, there are more children with chronic complicated health problems who survive yet remain dependent on sophisticated medical care. Intuitively, prompt recognition of the very ill child and the execution of the immediate and necessary interventions may be life saving. The ability to accomplish this requires a knowledge of the common culprits resulting in serious illness, an understanding of how they manifest in the physical examination, and an array of technical skills utilizing appropriate specially sized equipment. Furthermore, an understanding of child development and the ability to interpret the physical examination of the children of different ages is essential. This article will attempt to simplify this seemingly overwhelming task by considering a common thread in all critical illness.
The most recent introduction of an avian influenza A virus without reassortment into mammals occurred in 1979 when H1N1 strains could be isolated from diseased pigs in northern Europe. This newly introduced avian virus formed a stable lineage in pigs and, in the meantime, spread all over Europe. In 1991 highly pathogenic H1N1 strains closely related to a contemporary swine virus were isolated from turkeys of a breeding farm near Bremen, Germany. Outbreaks in several farms in Germany, France, and the Netherlands indicate that the "avian-like" swine viruses can easily be reintroduced into an avian population causing severe economical losses.
BACKGROUND: To date, there is little information available about the effect of cisapride and metoclopramide on gastroduodenal pressure waves and their space/time orientation. METHODS: Antroduodenal pressures (two antral, three duodenal recording sites) were measured in nine healthy volunteers. Cisapride (10 mg), metoclopramide (10 mg), and placebo were administered intravenously on different days in a randomized manner. RESULTS: During the interdigestive state cisapride increased the motility index significantly in the antrum (p < 0.05) and duodenum (p < 0.005), metoclopramide only in the duodenum (p < 0.01). Antroduodenal coordination was significantly (p < 0.01) improved by cisapride but not by metoclopramide. There is evidence of antroduodenal coordination even during the interdigestive state. After a liquid test meal an increase in the antroduodenal motility index (p < 0.05), in the rate of prograde antroduodenal peristalsis (p < 0.01), and in antroduodenal coordination (p < 0.01) was caused by cisapride but not metoclopramide. Both prokinetics decreased (p < 0.01) retrograde antroduodenal peristalsis. CONCLUSION: Cisapride significantly improves antroduodenal coordination and antroduodenal motility; metoclopramide seems to be less effective.
In the autumn of 1979 a severe influenza epizootic started among camels in Mongolia (Lvov et al., 1982; Viprosi Virusol. 27, 401-405.) Between 1980 and 1983 13 independent isolates of H1N1 viruses were obtained from diseased camels, which were virtually indistinguishable from the human A/USSR/90/77 strain by serological means. Two hundred and seventy-one samples of camel sera collected between 1978 and 1983 contained antibodies against the human A/USSR/90/77 isolate. After experimental infection of camels with some of these isolates, the animals developed similar symptoms as those found during natural infection: coughing, bronchitis, fever, discharge from nose and eyes. A genetic sequence analysis revealed that among the eight segments (genes) the PB1, HA, and NA genes were almost identical with allelic genes of the USSR/77 strain, and the PB2, PA, NP, M, and NS genes were almost identical with those of the A/PR/8/34 strain.
The nucleoprotein (NP) gene of influenza A viruses is decisive for separating two large individually evolving reservoirs in birds and humans. A phylogenetic analysis of the NP gene revealed that all mammalian influenza viruses originated--directly or indirectly--from an avian ancestor. The stable introduction of an avian influenza A virus into a mammalian species seems to be a relatively rare event, the latest one occurred in 1979 when such an avian virus was introduced into pigs in Northern Europe which gave rise to a new lineage. At least two concomitant events are required for such a new and stable introduction: (1) The new species has to become infected, and (2) a mutation in the polymerase complex has to establish a labile variant, which is prone to provide a large number of different variants, from which some can adapt rapidly to the new host (or to any unusual environments). Since such mutator mutations might be advantageous only during stress periods, variants with a less error prone polymerase might emerge again after adaptation. Examples for such fluctuations in terms of mutational and evolutionary rates are discussed in this brief review.
STUDY OBJECTIVE: To establish the frequency of use of pediatric emergency departments by adult patients and the spectrum of disease with which they present. DESIGN: Prospective, descriptive study and unblinded survey. SETTING: Children's Hospital pediatric ED. TYPE OF PARTICIPANTS: Seventy-two adult patients presenting to a pediatric ED during a two-year period and 31 pediatric emergency medicine fellowship directors. INTERVENTIONS: For each patient, we recorded demographic information, chief complaint, interventions by physicians, diagnosis, condition, and disposition after initial care. Pediatric emergency medicine fellowship training program directors were surveyed by telephone regarding their experiences with adult patients and the extent of adult emergency medicine training within their programs. MAIN RESULTS: Of the 72 adult patients evaluated, one third (22) were treated for trauma and the remaining 50 for medical illness. More than 40 different diagnoses were encountered, including stroke and myocardial infarction. Twenty patients (27.8%) required hospitalization, four (5.6%) in intensive care settings. Of the 31 fellowship directors surveyed, 27 (87.1%) indicated that adult patients had been managed in their EDs during the previous year. All but one reported that their fellowship programs incorporated between one and four months of adult emergency medicine in their curricula. CONCLUSION: Adults frequently present to pediatric EDs for both minor and serious illnesses. Training in adult emergency medicine should be a part of all pediatric emergency medicine fellowship programs.
Interest in pediatric emergency medicine has grown steadily during the past decade among pediatricians and emergency physicians. With the rapid proliferation of pediatric emergency medicine programs for pediatricians has come extensive and valuable experience with this type of fellowship education. As a result, the structure and scope of these programs have become increasingly well established. Because the number of pediatric emergency medicine fellowship programs for emergency physicians has yet to reach "critical mass," no similar de facto standards exist for these programs. The recent establishment of guidelines for pediatric emergency medicine subspecialty certification by the American Board of Emergency Medicine and the American Board of Pediatrics brings new importance to fostering such standards for the training for emergency physicians. To this end, we present a proposed pediatric emergency medicine fellowship program developed during a retreat that included physicians from an emergency medicine program and two pediatric hospitals. We also review some of the significant events that have occurred in the evolution of pediatric emergency care.
The purpose of this study is to examine the changes in the pediatric emergency medicine education of emergency medicine (EM) residents over the last decade. Questionnaires were mailed to the training directors of all EM residency programs. Sixty-five programs (79%) responded. While children represent 29 +/- 2% of all patients seen in the institutions surveyed, only 17 programs (26%) provide more than six months of pediatric education, ie, no increase in the last decade. EM residents frequently rotate through pediatric emergency departments (72%), inpatient pediatric wards (51%), and pediatric intensive care units (88%). Most physicians in charge of pediatric emergency medicine education are emergency medicine trained (75% vs 29% in 1981), and only 12% are pediatric emergency medicine fellowship trained. Despite several improvements and the increased satisfaction of program directors, the pediatric component of EM residents' training continues to be disproportionate to the number of children in the emergency medicine patient population. Specialists in pediatric emergency medicine should strive to play a more significant role in the pediatric education of EM residents.
The bacterial spectrum of blood cultures in a neonatal intensive-care unit was retrospectively assessed in a two-year study. Analysis of positive blood cultures showed a dominance of gram-positive bacteria, especially of coagulase-negative staphylococci. The resistance of these germs points to vancomycin as the most effective antibiotic. B-streptococci, germs that are dreaded especially in neonatology, were not found in any of the cases. Positive blood cultures were mostly in correlation with clinical symptoms, less so to the leukocyte count and/or C-reactive protein levels. There was no case of death directly caused by sepsis.
In summary, ED staff and local police departments should make a concerted effort to work together. The ED director should develop management protocols in conjunction with local police chiefs to plan strategies in advance. It is helpful to provide "orientation sessions," so that each group of professionals knows what to expect of the other. It may also be helpful to arrange tours of the ED so that police know where to go when they are called to the ED. All of these efforts should foster better care of children in the ED and will reduce tensions between the dedicated groups who work with such children.
In 66 children having undergone bone marrow transplantation (BMT) the occurrence of infections was studied retrospectively. Bacterial infections were mostly found in the early period after transplantation before marrow engraftment. The analysis of positive blood cultures showed a dominance of gram-positive bacteria, especially of coagulase-negative staphylococci. Cytomegalovirus (CMV) infections were most important, because of its high rate and the risk of CMV associated interstitial pneumonia (IP), two patients suffered from. Infections from herpes simplex virus (HSV), varizella zoster virus (VZV) and Epstein Barr virus (EBV) had no influence on prognosis. In fungal infections the systemic aspergillosis was the most important complication. To increase the effectiveness and safety of therapy the serum levels of antibiotics and antifungal drugs should be determined.
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There is evidence that the nucleoprotein (NP) gene of the classical swine virus (A/Swine/1976/31) clusters with the early human strains at the nucleotide sequence level, while at the level of the amino acid sequence, as defined by consensus amino acids and in functional tests, its NP is clearly "avian like." Therefore it was suggested that the Sw/31 NP had been recently under strong selection pressure, possibly caused by reassortment with other avian influenza genes, whose gene products have to cooperate intimately with NP (Gammelin et al., 1989. Virology 170, 71-80). This suggestion has been investigated by sequencing the genes of internal and nonstructural proteins of Sw/31. The data on these sequences and on the phylogenetic trees are not in accordance with that suggestion: all these genes cluster with the early human strains at the nucleotide level while, at the level of the amino acid sequence, most of them are more closely related to the avian strains, thus resembling NP in this respect. This indicates that these genes rather evolved concomitantly with the NP gene. Our data are in agreement with the suggestion that, at about the time of the Spanish Flu (1918/19), a human influenza A (H1N1) virus entered the pig population. Furthermore, it is known that the NP of the human influenza A viruses--in contrast to that of the avian and swine strains--has been under strong selection pressure to change (Gammelin et al., 1990. Mol. Biol. Evol. 7, 194-200. Gorman et al., 1990a. J. Virol. 64, 1487-1497). Thus, after transfer of a human strain into pigs, the selection pressure might be released, enabling the NP and the other genes of the swine virus to evolve back to the optimal avian sequences, especially at the functionally important consensus positions. The swine influenza viruses circulating since 1979 in Northern Europe--represented by A/Swine/Germany/2/81 (H1N1)--have all genes, so far examined, derived from an avian influenza virus pool and are different from the classical swine viruses.
Phylogenetic trees were constructed using 38 sequences of the A group and 10 sequences of the B group of the NS gene of influenza A viruses. Within the A group we found avian as well as mammalian influenza a viruses, while within the B group exclusively avian strains were found. The avian and human NS genes of the A group were derived from a common ancestor existing at about 1912. At 13 positions of the amino acid sequences of the NS1 protein two subtypes of the A group can be differentiated, a human and a non-human subtype. Starting at the time of the introduction of an avian PB1 gene into human strains during the antigenic shift at 1957 the NS1 protein of the human strains came under an enhanced selection pressure which might indicate a cooperation of the NS1 protein with and adaptation of the NS1 protein on the newly introduced PB1 gene. Such a selection pressure on the NS2 protein is completely missing. Comparison of all sequences of the NS1 protein revealed four highly conserved regions within the amino-terminal half of the molecule. One of this regions seems to contain the nuclear migration signal. The carboxy-terminal half is completely variable and seems to be dispensable.