[Small intestinal tumors with skenoid fibers and von Recklinghausen neurofibromatosis].
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Female↗
Biomedical subjects
L Ludwig
Publications and source records attributed to L Ludwig.
Analysis of p53 mutations in a large series of lymphoid hematologic malignancies of childhood.
p53 mutations are found in a wide variety of cancers, including hematologic malignancies. These alterations apparently contribute to development of the malignant phenotype. We analyzed a large series of lymphoid (330 cases) and a smaller series of myeloid (29 cases) malignancies of childhood for p53 mutations by single-strand conformational polymorphism (SSCP) following polymerase chain reaction. Samples with abnormal SSCP were reamplified and analyzed by direct sequencing method. p53 mutations were detected within the known mutational hotspots (exons 5 to 8) in 8 of 330 lymphoid malignancies, and in none of 29 myeloid malignancies, showing that the frequency of p53 mutations in childhood lymphoid malignancies was very low (8 of 330 cases [2%]). Four of these patients had very aggressive, fatal acute lymphocytic leukemia (ALL). None of 13 infants and none of 48 patients with T-lineage leukemia had detectable p53 mutations in their ALL cells. Exceptionally, p53 mutations were comparatively frequent in a small sample of B-cell non-Hodgkin's lymphomas (2 of 8 cases). Mutations were detected in samples from two patients with ALL at relapse; these were not detected in samples at initial diagnosis from the same patients, suggesting that p53 mutations may be associated with progression to a more malignant phenotype. Seven of eight alterations of p53 were missense mutations, and seven of eight samples may be heterozygous for the mutant p53, indicating that p53 protein may act in a dominant negative fashion.
Adolescent↗
Recent health sciences library building projects.
The Medical Library Association's third annual survey of recent health sciences library building projects identified fourteen libraries planning, expanding, or constructing new library facilities. Three of five new library buildings are freestanding structures where the library occupies all or a major portion of the space. The two other new facilities are for separately administered units where the library is a major tenant. Nine projects involve additions to or renovations of existing space. Six projects are in projected, predesign, or design stages or are awaiting funding approval. This paper describes four projects that illustrate technology's growing effect on librarians and libraries. They are designed to accommodate change, a plethora of electronic gear, and easy use of technology. Outwardly, they do not look much different than many other modern buildings. But, inside, the changes have been dramatic although they have evolved slowly as the building structure has been adapted to new conditions.
Architecture↗
Mutations within the FLR exon of NF1 are rare in myelodysplastic syndromes and acute myelocytic leukemias.
A mutational hotspot in the neurofibromatosis 1 (NF1) gene has recently emerged from the analysis of different malignancies including one patient with myelodysplastic syndrome (MDS). In these cases, Lys 1423 in the GTPase-activating protein (GAP)-related domain of NF1 is substituted which causes a significant reduction of intrinsic GAP activity. We studied 57 MDS patients and 27 cases of acute myelocytic leukemia (AML) for mutations at codon 1423 in the so-called FLR exon of NF1 by an assay based on restriction enzyme digestion. We investigated the entire FLR exon and its flanking intron sequences using single-strand conformation polymorphism (SSCP) analysis of polymerase chain reaction (PCR) products and sequencing. None of the cases exhibited a codon 1423 mutation. However, a patient with chronic myelomonocytic leukemia (CMML) showed a 3 bp deletion within the splice acceptor region in front of the FLR exon. These data suggest that NF1 exon FLR mutations contribute infrequently to the development of MDS and AML.
Acute Disease↗
P53 mutations in myelodysplastic syndromes.
Point mutations in the p53 tumor-suppressor gene are the most frequently identified genetic alterations in human malignancies. In order to evaluate the role of p53 mutations in the multistep process of leukemogenesis we studied 61 patients with myelodysplastic syndromes using single-strand conformation polymorphism analysis of polymerase chain reaction products as well as direct sequencing. Mutant alleles were observed in 1/14 refractory anemia with excess of blasts (RAEB) and 2/5 RAEB in transformation. The three mutations represented G:C to A:T transitions at codon 141 (exon 5) and codons 245 and 248 (exon 7), respectively. These data suggest that p53 mutations may contribute, albeit rarely, to the development of preleukemic disorders of the myeloid cell lineage.
Anemia, Refractory↗
Controlled trial of Giardia lamblia: control strategies in day care centers.
BACKGROUND: Strategies for control of Giardia lamblia in day care differ in numbers of children treated and in costs to parents and day care operators. The effectiveness of these strategies has not been systematically evaluated. METHODS: We conducted a prospective randomized controlled trial comparing three strategies for control of Giardia in infant-toddler day care centers: Group 1, exclusion and treatment of symptomatic and asymptomatic infected children; Group 2, exclusion and treatment of symptomatic infection only; Group 3, exclusion and treatment of symptomatic infection, treatment of asymptomatic infection in the center. The study included 31 day care centers with 4180 child-months of observation. Giardia prevalence was determined before intervention and 1, 2, 4, and 6 months later; new infants and toddlers were tested on admission. RESULTS: Initial Giardia prevalences were 18% to 22% in the three groups. Giardia was identified in 10.5% of 676 new infants and toddlers entering study day care centers during the 6-month follow-up. Giardia prevalences by intervention group were 8%, 12%, and 7% at 1 month, and 7%, 8%, and 8% at 6 months. CONCLUSIONS: The stricter intervention resulted in greater cost in terms of child day care and parents' work days lost, but did not result in significantly better control of Giardia infections in this day care environment.
Child Day Care Centers↗
User attitudes toward end-user literature searching.
A survey to determine attitudes toward end-user searching was made at Loyola University's Medical Center Library using MEDIS, an online full-text and bibliographic medical retrieval system. One hundred forty-one completed questionnaires were analyzed for this report. Information was collected on user familiarity with computers, end-user training, system use, mechanics of searching, and attitudes toward future use. Computer familiarity was highest among the faculty users. Ninety percent of the respondents saw librarians as a crucial agent in training and in providing end-user assistance. Respondents identified five major reasons for using the system: helpfulness, convenience, time savings, rapid feedback, and presentation of needed information. Searching the MEDLINE database rather than the full-text database was the search method of choice. Continued use of both mediated and end-user searching was intended by most of the respondents. Survey results support a perceived need for end-user searching and confirmed recommendations of the Association of American Medical Colleges on medical information science skills.
Attitude of Health Personnel↗
Vascularized fibular epiphyseal transfer. A clinical study.
In a review of the experimental and clinical literature on nonvascularized and vascularized epiphyseal transfer, experience with eight patients with free vascularized fibular epiphyseal transfer suggests that transfer of bone with an open epiphysis offers some potential for growth in either congenital abnormalities or epiphyseal arrest secondary to trauma and infection. In four cases, premature epiphyseal closure prevented appreciable growth. In the other four, the epiphyses remain open and the transferred bones continue to grow. Although the procedure is experimental, the results of combined epiphyseal and metaphyseal vessel transfer with a skin island as a monitor of viability, warrant further investigation.
Arm↗
Central and autonomic nervous system side effects of ketanserin.
A placebo controlled, randomized, double-blind cross-over study was carried out in 7 healthy volunteers in order to study the central and autonomic nervous system side effects of ketanserin in comparison to clonidine. Psychometric performance was assessed as well as electroencephalographic recordings (EEG), saliva production, mean arterial blood pressure (MAP) and pulse rate under placebo conditions (P, 10 ml saline), following 0.15 mg/kg ketanserin or 2 micrograms/kg clonidine i.v. administration. The sedation index as well as the deceleration of EEG frequencies clearly expressed sedation following both, ketanserin and clonidine. Saliva production was significantly decreased by ketanserin (p less than 0.05) and clonidine (p less than 0.01), respectively. MAP was only very slightly reduced by ketanserin, while clonidine caused a small but significant decrease (p less than 0.0001). The pulse rate changes did not reach a clinically important extent. Thus, sedation as main central nervous system side effect and reduction in salivation as autonomic nervous system side effect of ketanserin could be clearly quantified in comparison to placebo and clonidine.
Adult↗
Reversal of slow-wave sleep by benzodiazepine antagonist Ro 15-1788.
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Adult↗
Pharmacodynamic interaction between midazolam and a specific benzodiazepine antagonist in humans.
The pharmacodynamic interaction between midazolam and the specific benzodiazepine antagonist Ro 15-1788 has been investigated in six healthy male volunteers. Hypnotic steady-state concentrations of midazolam (55 +/- 11 ng/mL; mean +/- SD) have been achieved rapidly by an intravenous bolus of 0.07 mg/kg and maintained by an individual but constant infusion rate of 0.025 to 0.04 mg/kg/hr for eight hours. Following a two-hour control period, the antagonist (2.5 mg) or the solvent were injected double-blind in random order. Three hours later, the other medication was administered. Whereas plasma levels of midazolam remained constant throughout the complete eight-hour trial (Clearance = 670 +/- 96 mL/min) concentrations of Ro 15-1788 declined rapidly with an elimination half-life between 0.7 and 1.8 hours and a total plasma clearance of 702 +/- 235 mL/min. Concentrations of Ro 15-1788 approached the analytic limit of 2 ng/mL within three hours. The pharmacodynamic response to midazolam and the antagonist was assessed by a sedation index using visual analogue scales, reaction time (RT) measurements, and transformed Fourier analysis of the power spectrum of the recorded electroencephalogram (EEG). About 30 to 45 seconds following the injection of Ro 15-1788, hypnotic action of midazolam was completely reversed as visualized by return to alpha rhythm in the EEG, shortening of prolonged RT, and normalization of the elevated sedation index. The antagonistic action lasted for about two to three hours. The abrupt arousal from sleep was not associated with any unpleasant sensations, however, three subjects experienced a profound perspiration for about ten minutes following the injection of Ro 15-1788.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Apparent superiority of H2-receptor stimulation and simultaneous beta-blockade over conventional treatment with beta-sympathomimetic drugs in post-acute myocardial infarction: cardiac effects of impromidine--a new specific H2-receptor agonist-in the surviving catecholamine-insensitive myocardium.
Left ventricular infarction (AMI) was produced in experimental animals and the contractile response to beta-adrenergic and H2-histaminergic stimulation by isoproterenol and impromidine tested in the isolated perfused heart preparation. Adenylate cyclase activity as well as binding characteristics of [3H]-dihydroalprenolol ([3H]-DHA), [3H]-methyl-tiotidine ([3H]-TIOT) and [3H]-quinuclidinyl benzilate ([3H]-QNB) to cardiac beta 1-, H2- and cholinergic muscarinic receptors were determined in sarcolemmal membrane preparations of the right ventricle of the same hearts. In addition, an attempt was made to elucidate the therapeutic value of post-AMI treatment with impromidine in the presence and absence of beta-blockade, in contrast to administration of prenalterol and the conventional therapy with beta-sympathomimetic drugs, e.g. dobutamine. Three days post-AMI the dose-response curve for isoproterenol of right ventricular dP/dtmax was significantly depressed, while the inotropic effect of impromidine was not impaired. Stimulation of adenylate cyclase activity by isoproterenol was reduced by 80% whereas impromidine and NaF stimulation rates were unaltered. Receptor-binding studies indicated a 90% loss and 10-times lowered affinity (KD) of the remaining beta-receptors while specific [3H]-TIOT- and [3H]-QNB-binding was unchanged. Administration of dobutamine increased mortality rates and extension of infarct size, led to a further decrease in contractile response to isoproterenol, induced complete insensitivity of adenylate cyclase to isoproterenol stimulation and caused pronounced additional reduction of number and affinity of [3H]-DHA-binding sites. In contrast, all above alterations were prevented by treatment with either prenalterol or combined administration of impromidine plus metoprolol. It is concluded, that these alterations in the non-ischemic, uninvolved myocardium post-AMI are the result of catecholamine-induced specific damage of sarcolemmal beta-receptors. Furthermore, treatment with H2-agonists in combination with beta-blocking agents may have beneficial effects, whereas conventional therapy with beta-sympathomimetic drugs tends to worsen the already depressed function of the beta-adrenergic stimulation mechanism.
Adenylyl Cyclases↗
Stress protective effects during steady-state conditions of bromazepam.
In 10 young, healthy male volunteers the stress-protective efficacy of bromazepam (orally 3 mg bid) was investigated double-blind (vs placebo) during steady state. Physical and mental stress was induced by ergometer (125 Watt for 5 minutes) and delayed auditory feedback, respectively. Stress response was measured biochemically (plasma concentrations of epinephrine, norepinephrine and dopamine), physiologically by monitoring heart rate and blood pressure and subjectively (by visual analogue scales). Both stress-tests were associated with a significant increase in plasma levels of epinephrine and norepinephrine. Whereas the applied dose of bromazepam did not impair performance of the subjects, it demonstrated some protective effects in terms of a diminished elevation of the cardiovascular parameters, especially a reduced increase of the plasma levels of epinephrine (p less than 0.05) and norepinephrine (p less than 0.10). In conclusion, it can be assumed that endocrine and cardiovascular response to physical and mental stress can be attenuated by steady-state bromazepam.
Adolescent↗
Relationships between plasma levels and psychological effects of benzodiazepines.
In the past, pharmacokinetics of benzodiazepines have been extensively described. However, knowledge about relationships between their plasma levels and pharmacodynamic effects are scanty. Therefore, we investigated under several experimental conditions the disposition and the psychological response of the short acting midazolam (single dose 0,075 mg/kg i.v. and 15 mg po) and of the moderate long acting oxazepam (30 mg/die for 5 days). Psychological and psychomotoric effects were evaluated by analogue scales (sedation index), d-2 letter cancellation test, reaction time, critical flicker fusion frequency and adjective mood list. In general, good correlations were found between those tests and plasma levels, especially for midazolam. Analogue scales and reaction-time proved to be most useful in our "effect-kinetic" approach.
Adult↗
Effect of midazolam on sleep.
Midazolam (15 mg p.o.) was compared with placebo and oxazepam (15 mg) in 12 healthy volunteers and in seven patients suffering from sleep disorders in a single-blind cross-over study. Each treatment period lasted for seven days. The last two nights were spent in a sleep laboratory to evaluate the efficacy of the three compounds. The drugs were given to the patients every day and to the volunteers only on the recorded nights immediately before going to bed. The subjects rated their quality of sleep every morning after administration. Midazolam shortened (P = 0.025) the sleep latency to first stage 2 (t2 = 29 min) compared with placebo (t2 = 58.7) min and oxazepam (t2 = 55.4 min) in the group of patients; in the group of volunteers t2 was shortened (P = 0.05) only by midazolam (t2 = 17.2 min) compared with placebo (t2 = 24.6 min). REM suppression was not found in the group of patients, while sleep stages 3 + 4 were slightly reduced. However, a suppression of REM by midazolam (P = 0.025) and oxazepam (P = 0.01) was observed in the volunteers compared with placebo. The effects of midazolam seemed to be related to its pharmacokinetics. The drug increased the amount of stage 3 + 4 (P = 0.01) and suppressed REM (P = 0.005) compared with oxazepam and placebo, only during the first 3 h, when it was measurable in plasma. Midazolam was rated by the patients more favourably than oxazepam (P = 0.025) and placebo (P = 0.05). The volunteers noted no difference amongst the three treatments, but reported hangover effects after oxazepam.
Anti-Anxiety Agents↗
Staff management and motivation.
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Humans↗
Deleterious effects of cimetidine in the presence of histamine on coronary circulation. Possible clinical implications in anaphylactic states in individuals with coronary heart disease.
The present study characterizes effects of histamine in the presence of the H2-antagonist cimetidine on the coronary circulation of the isolated perfused spontaneously beating guinea pig heart. Infusion of histamine (2 x 10(-8) mol/1-5 x 10(-6) mol/l) induced a dose-dependent coronary dilation, comparable to the effect of isoproterenol and two highly-selective H2-agonistic compounds, impromidine and dimaprit. In the presence of cimetidine (5 x 10(-6) mol/l), however, coronary response to histamine was reversed in a manner that a dose-dependent coronary constriction occurred with coronary spasm and a flow rate approaching zero at histamine concentrations above 8 x 10(-7) mol/l, whereas the dilatory effect of impromidine and dimaprit was completely antagonized. In contrast, the histamine-induced constriction in the presence of cimetidine could be nearly abolished by additional infusion of the H1-antagonistic compound mepyramine (5 x 10(-5) mol/l). Is is concluded that H1- and H2-receptors are present in the coronary smooth muscle, H1-receptors mediating constriction and H2-receptors mediating coronary dilation. Speculation is provided that histamine may have hazardous effects in anaphylactic states if cimetidine is administered simultaneously, e.g., to prevent or cure peptic ulcer. Other possible clinical implications will be discussed.
Anaphylaxis↗
Cardiac contractile and metabolic effects mediated via the myocardial H2-receptor adenylate cyclase system. Characterization of two new specific H2-receptor agonists, impromidine and dimaprit, in the guinea pig and human myocardium.
The present study chartacterizes myocardial effects of two new histaminergic H2-receptor specific compounds, impromidine, and dimaprit, on cardiac contractile and metabolic parameters of the guinea pig heart and human papillary muscle in comparison to the well-known effects of catecholamines. Impromidine and dimaprit produced a dose-dependent stimulation of the right and left ventricular contractile force in the isolated perfused biventricular catheterized guinea pig heart with maximal stimulation rates equal to those of isoproterenol. Hemodynamic equieffective doses of isoproterenol (2.8X10(-9) mol/l), histamine (1.1X10(-5) mol/l), impromidine (4.6X10(-7) mol/l, and dimaprit (8.5X10(-6) mol/l) induced nearly identical increases in tissue concentrations of c-AMP. All compounds dose-dependently enhanced the activity of the myocardial adenylate cyclase with very similar KA-values in a particulate sarcolemmal membrane preparation of both guinea pig ventricles and human papillary muscles. No effect of either compound was seen on cardiac phosphodiesterase activity. Selective administration of the beta1-blocking agent metoprolol and the H2-receptor antagonist cimetidine clearly discriminates two independent receptors linked to the sarcolemmal adenylate cyclase system in the guinea pig and human myocardium. This is further supported by results obtained from beta-receptor-binding studies in which an interference of impromidine and dimaprit with the stereospecific binding of (-)[3H]-dihydroalprenolol to cardiac beta-receptors could be definitely excluded. The possible therapeutic role of both H2-agonists on the non-ischemic, surviving myocardium, which is transiently refractory to beta-adrenergic stimulation by catecholamines after myocardial infarction, will be discussed.
Adenylyl Cyclases↗