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Biomedical subjects

E Christian

Publications and source records attributed to E Christian.

17 recordsLinked to original sources
PubMed1997

Vaccine antigen interactions after a combination diphtheria-tetanus toxoid-acellular pertussis/purified capsular polysaccharide of Haemophilus influenzae type b-tetanus toxoid vaccine in two-, four- and six-month-old infants.

OBJECTIVE: The safety and immunogenicity of a diphtheria-tetanus toxoid-acellular pertussis vaccine (DTaP; Trepedia)/Haemophilus influenzae b polysaccharide (PRP-T; ActHib) combined vaccine (TriHibir; Pasteur Mérieux Connaught) was compared with DTaP and PRP-T given at the same visit but at separate sites in a prospective multicenter, open label trial. METHODS: Infants were randomized to four groups (three consistency lots of DTaP/PRP-T vs. one of the consistency lots given as separate vaccines); injections were administered at 2, 4 and 6 months of age. Pre-Dose 1 and post-Dose 3 sera were assayed for antibody titers against all antigens. Reactions to the vaccinations were assessed by parent questionnaire for 30 days after each injection visit. RESULTS: Four hundred eighty-five infants were enrolled; 296 evaluable infants were included in the DTaP/PRP-T group compared with 70 infants in the DTaP and PRP-T vaccine group. Infants who received the combined vaccine had higher post-Dose 3 geometric mean antibody titers to diphtheria antitoxin (P < 0.01) and pertussis filamentous hemagglutinin (P < 0.05) and lower geometric mean antibody titers to tetanus antitoxin (P < 0.05) and Haemophilus influenzae b (Hib) polysaccharide (PRP) (P < 0.05). The geometric mean anti-PRP antibody titer in the DTaP/PRP-T group was 4.3 micrograms/ml compared with 7.0 micrograms/ml in the separate vaccine group (P < 0.05), and the percentage of infants with antibody titers > or = 0.15 and 1 microgram/ml were, respectively, 95 and 86%, whereas they were 100% for both titers in the separate vaccines group. DTaP/ PRP-T vaccine given concomitantly or 1 month apart from hepatitis B vaccine and oral poliomyelitis vaccine caused no significant differences in immunogenicity or safety. The safety assessments for the DTaP/PRP-T vaccine showed no consistent differences in systemic or local injection site reactions compared with DTaP and PRP-T administered separately. CONCLUSION: Although the antibody responses to tetanus and Hib polysaccharide in the evaluated DTaP/PRP-T combined vaccine were significantly lower than those seen after separate DTaP and PRP-T administration, the combined vaccine elicited an immune response against diphtheria, tetanus, pertussis and Haemophilus influenzae b likely to confer protection.

Analysis of Variance↗
PubMed1991

An axial binding site in the Tetrahymena precursor RNA.

Previous studies allow the construction of three distinct models of the binding of G and arginine within the active site of the Tetrahymena self-splicing preribosomal precursor RNA. These models (base triple, axial I and axial II) are now distinguished by measurements on the specificity of RNAs with nucleotide substitutions at positions spanning the site. Because the semi-conserved unpaired nucleotide 263 has no effect on substrate or inhibitor selection by the Tetrahymena RNA we conclude that the axial I model is improbable. In contrast, data with substituted RNAs and nucleoside analogs suggest that nucleotide 265 makes a hydrogen bond with the substrate. Accordingly the active site appears axial because substrate contacts exist at more than one nucleotide on the 5' side of the P7 helix. The effects of this hydrogen bond are observable in cases where the donor or acceptor is on the RNA, whether nucleotide 265 is a purine or pyrimidine, or whether nucleotide 265 is mispaired, wobble paired or normally paired. This pattern is consistent with the axial II model. Molecular dynamics and energy minimization calculations lead to the same conclusions as these site-directed substitutions; the base triple and axial I models are unstable dynamically. Under thermal agitation, the third model site (axial II) is transformed to a related, but more stable structure, axial III. The axial III active site is characterized by the extrusion of the conserved bulged base 263 from the P7 helix, a semi-pocket for G base formed by stacking of nucleotide 262, and formation of all bonds to the G base originally proposed for both the base triple and axial II sites. Because of these hydrogen bonds the axial III site is also consistent with data on enzymatic specificity. The axial III model indicates an unforeseen capacity for pocket formation within the groove of an RNA helix, suggests that the site may be unusually flexible, and bears on a hypothesis concerning the origin of the genetic code.

Animals↗
PubMed1991

Selection of small molecules by the Tetrahymena catalytic center.

The catalytic center in group I RNAs contains a selective binding site that accommodates both guanosine and L-arginine. In order to understand the specificity of the RNA for small molecules, we analyzed 6 RNAs that vary in this region. Specificity for nucleotides resides substantially in G264 rather than its paired nucleotide C311, and is expressed substantially in Km, with comparatively little variation in kcat. kcat is not notably perturbed even for RNAs with mispairs in the active-site helix. For 5 of 6 sequences, effects of RNA substitutions on arginine binding and GTP reactivity are proportional, confirming that arginine contacts a subset of the groups occupied by G. As a result of particular mutations, reaction with GTP is decreased, and reaction with the natural nucleotides UTP and ATP is enhanced. Molecular modeling of these effects suggests that exceptionally flexible placement of reactants may be an essential quality of RNA-catalyzed splicing. The specificity of the intron can be rationalized by a type of binding model not previously considered, in which the G/arginine site includes adjacent nucleotides (an 'axial' site), rather than a single nucleotide, G264.

Amino Acids↗
PubMed1989

Sounds of silence--coping with hearing loss and loneliness.

The vast majority of people will suffer presbycusis during the aging process. This hearing loss has potential social consequences, which place these individuals at risk for loneliness. Nurses need to encourage thorough audiological examination and follow through on recommendations to improve hearing. The use of hearing aids needs to be encouraged. A suggested model of interaction among variables influencing loneliness identifies areas amenable to nursing intervention. Frequency of significant interaction and motivation to engage in interactions represent two important variables that influence loneliness.

Adaptation, Psychological↗
PubMed1984

Therapeutic effects of single-push or fractionated injections or continuous infusion of oxazaphosphorines (cyclophosphamide, ifosfamide, Asta Z 7557).

This report describes some experimental and clinical studies showing the following: (1) in animals under protection of mesna the dose of ifosfamide (Ifo) can be increased significantly; (2) fractionated administration of Ifo, cyclophosphamide (CPA), or the stabilized metabolite of cyclophosphamide (ASTA Z 7557) is less toxic than single push-injection of the same total daily dose and therapeutically more effective; and (3) in humans under the protection of mesna the continuous infusions of ifosfamide over 5 days leads to an increase of the MTD compared with single daily short-term infusion and responses in some solid tumors, e.g., soft tissue sarcomas.

Animals↗
PubMed1984

Preclinical evaluation of toxicity and therapeutic efficacy of a stabilized cytostatic metabolite of cyclophosphamide (ASTA Z 7557, INN mafosfamide).

ASTA Z 7557 is a stabilized cytostatic metabolite of cyclophosphamide which forms crystals at room temperature and releases 4-OH-cyclophosphamide in aqueous solution. The LD50/30 in mice after push injection is 417 mg/kg, after fractionated administration (q 6 hours X 4) 794 mg/kg. Daily treatment times 5 gives a LD50/30 value of 200 mg/kg. Depression of nucleated bone marrow cells and of leukocytes in the peripheral blood is observed after treatment. Recovery is slow. This holds true for push and fractionated administration. ASTA Z 7557 is a powerful cytostatic drug for treatment of an Ehrlich ascites tumor, a Lewis lung and a mammary carcinoma. Of two human tumor xenografts a malignant amelanotic melanoma responded with slight growth delay, whereas a gastric cancer did not.

Animals↗
PubMed1983

[Modification of an Ehrlich ascites tumor growth by various standardized feedings].

Oral feeding of mice with hypercaloric diets inhibited growth of a hyperdiploid Ehrlich ascites tumor significantly and modified proliferation kinetics of tumor cells if feeding started 7 days before tumor transplantation. Furthermore, the tumor take rate was significantly reduced. The 4 hypercaloric diets contained as main energy sources carbohydrates, or unsaturated fatty acids, or saturated fatty acids, or a mixture of these substrates. Inhibition of tumor growth was not observed if hypercaloric feeding started on the same day the tumor transplantation occurred. Tumor bearing animals lived significantly longer compared to controls if they are on a hypercaloric diet with unsaturated fatty acids as main energy source. Survival was not influenced by the time feeding started. That means that partial prevention of cachexia was the main reason for longer survival. Feeding with a diet poor in proteins led in both experimental sets to a statistically not significant shortening of the median survival time compared to controls.

Animals↗
PubMed1983

Evaluation of clinical severity in sickle cell disease.

For a severity classification of sickle cell disease to be accepted, it is necessary that clinicians agree upon relative disease severity between patients. This condition was shown to be satisfied for a randomly selected group of patients evaluated by four persons. All rank correlation coefficients between observer pairs were highly significant. Representative severity indices based on history and recent hospital events also correlated significantly with evaluator ranking. The results show that, in principle, a classification of sickle cell disease patients by severity is possible. Such a classification would be most useful to evaluate the prognostic significance of particular signs or symptoms, or the success of various treatments in affecting severity of disease.

Adolescent↗
PubMed1982

Evoked potentials in the dentate gyrus reflect the retention of past sensory events.

Averaged sensory evoked potentials were recorded from the outer molecular layer of the dentate gyrus (OM AEP) in freely moving rats trained to criterion performance in a two-tone differential discrimination paradigm. OM AEPs showed consistent fluctuations in amplitude based on the acquired significance of the tone through their association with reward (CS+) or non-reward (CS-). However, the relationship between tone significance and OM AEP configuration was dependent upon the sequence of trials preceding the evoked potential, irrespective of whether the potential was evoked by a CS+ or CS-. Specifically, when the preceding sequence contained an increased number of CS- trials, the amplitude of the initial negative component (N1) of the OM AEP was increased, while that of the slower (N2) component was reduced; conversely, when the preceding sequence contained an increased number of CS+ trials, the amplitude of N1 was reduced, while that of N2 was increased. The results suggest that the transmission of sensory information into the dentate gyrus is biased by prior experience.

Animals↗
PubMed1981

Dentate granule cell discharge during conditioning. Relation to movement and theta rhythm.

The activity of dentate granule cells (g-cells) was recorded in chronic rats during single-tone sensory discrimination performance. Attempts to correlate the discharge pattern of dentate g-cells with (1) the onset of the conditioned tone stimulus, (2) movements of the animals during the conditioning trials, (3) the occurrence of the reinforced response, and (4) the presence or absence of theta rhythm during the trial revealed several features of g-cell discharge during performance of operant sensory discrimination. The most consistent finding was that g-cells were driven at short latencies (40-60 ms) by the onset of the tone stimulus in the absence of detectable body movements. A subsequent, less intense sustained discharge of g-cells was shown to be unrelated to the onset of (1) conditioned movements during the trial, or (2) the execution of the conditioned response. Thus neither phase of g-cell discharge to the tone stimulus appeared to be a direct correlate of inadvertently or directly conditioned movements in this experimental paradigm. Theta rhythm, which accompanied certain movements prior to the execution of the operant response, did not correlate with the initial phase of g-cell discharge but appeared to modulate the subsequent phase of sustained g-cell activity.

Animals↗
PubMed1980

Experimental investigations on a sequential combination chemotherapy protocol.

This paper deals with experimental investigations concerning the composition of a cytostatic three-drug-protocol in diploid Ehrlich-Ascites-Tumor (EAT) cells in vivo at a far advanced stage of the disease. Hydroxyurea (HU) and vincristine (VCR) were used in very low doses to induce a modification of the growth pattern of tumor cells alike partial synchronization. Adriamycin (ADM) was selected as cytocidal drug during DNA synthesis of the partially synchronized cells. It was found that the sequential combination of HU and VCR (first HU and 12 h thereafter VCR) caused the greatest alteration of growth pattern compared with other combination protocols. A further statistically significant increase of the degree of synchrony was observed after a second VCR administration -- 22 h after HU. By means of this protocol the EAT was subdivided into two proliferating subpopulations, a diploid and tetraploid one. The tetraploid population resulted from surviving cells being not able to perform dytokinesis correctly, so that polynuclear cells and cells with a large single nucleus containing tetraploid DNA values were created. With respect to therapy, the administation of ADM at the time of DNA synthesis of the partially synchronized cells resulted in a statistically significant prolongation of the mean survival time and in 30% of cures of the animals. The dosage of ADM was 2.6 mg/kg, i.e., a nonlethal dose (50% of the LD10). Other combinations, i.e., simultaneous or reversed sequential combinations, did not show any therapeutic improvement compared to single drug therapy of ADM.

Animals↗
PubMedDate not supplied

Downsizing the physician workforce.

OBJECTIVE: To estimate the need for downsizing the physician workforce in a changing health care environment. METHODS: First assuming that 1993 physician-to-population ratios would be maintained, the authors derived downsizing estimates by determining the annual growth in the supply of specialists necessary to maintain these ratios (sum of losses from death and retirement plus increase necessary to parallel population growth) and compared them with an estimate of the number of new physicians being produced (average annual number of board certificates issued between 1990 and 1994). Then, assuming that workforce needs would change in a system increasingly dominated by managed care, the authors estimated specialty-specific downsizing needs for a managed care dominated environment using data from several sources. RESULTS: To maintain the 1993 199.6 active physicians per 100,000 population ratio, 14,644 new physicians would be needed each year. Given that an average of 20,655 physicians were certified each year between 1990 and 1994, at least 6011 fewer new physicians were needed annually to maintain 1993 levels. To maintain the 132.2 ratio of active non-primary care physicians per 100,000 population, the system needed to produce 9698 non-primary care physicians per year, because an average of 14,527 new non-primary care physicians entered the workforce between 1990 and 1994, downsizing by 4829, or 33%, was needed. To maintain the 66.8 active primary care physicians per 100,000 population ratio, 4946 new primary care physicians were needed per year, since primary care averaged 6128 new certifications per year, a downsizing of 1182, or 20% was indicated. Only family practice, neurosurgery, otolaryngology, and urology did not require downsizing. Seventeen medical and hospital-based specialties, including 7 of 10 internal medicine subspecialties, needed downsizing by at least 40%. Less downsizing in general was needed in the surgical specialties and in psychiatry. A managed care dominated-system would call for greater downsizing in most of the non-primary care specialties. CONCLUSION: These data support the need for downsizing the nation's physician supply, especially in the internal medicine subspecialties and hospital support specialties and to a lesser extent among surgeons and primary care physicians.

Health Services Needs and Demand↗