[Development of antibiotic resistance of Pneumococcus. A new way for prescribing antibiotics in pediatrics].
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Biomedical subjects
Publications and source records attributed to R Cohen.
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The case of a 36-year old man with IgA kappa multiple myeloma in whom meningeal myelomatosis developed is reported, and a brief review of previously published cases is made. Meningeal involvement develops in patients with high tumoral mass myeloma. Because of its poor prognosis, central nervous system chemoprophylaxis based on clinical and cerebrospinal fluid data, and systemic treatment according to severity, is suggested.
The calcitonin/calcitonin gene-related peptide gene expresses two different mRNAs by tissue-specific alternative processing. The calcitonin mRNA is produced in thyroid C cells by splicing of the first three exons to the fourth polyadenylated exon. It encodes a protein precursor containing an amino-terminal peptide, calcitonin, and a carboxyl-terminal peptide (CCP I). Calcitonin gene-related peptide (CGRP) mRNA is produced in neuronal cells by splicing of the three common exons to the fifth exon and the polyadenylated sixth exon, leading to the production of a CGRP precursor. Our studies concerning the expression of the calcitonin/CGRP gene in human medullary thyroid carcinoma revealed the presence of a new RNA transcript. Amplification by polymerase chain reaction and direct sequencing showed that the novel transcript is composed of exons 1, 2, and 3, part of exon 4, exon 5, and a polyadenylated exon 6. This transcript contains an open reading frame coding for the known amino-terminal and calcitonin peptides, as well as for a novel calcitonin carboxyl-terminal peptide, CCP II. This third alternative pathway utilizes an internal donor site within the exon coding for calcitonin. The presence of CCP II was demonstrated in plasma and thyroidal tissues of medullary thyroid carcinoma patients, implying that this novel mRNA is actively translated in medullary thyroid carcinoma.
Interaction of cloned yeast, drosophila, and human transcription factor IID (yTFIID, dTFIID, and hTFIID, respectively) with the adenovirus 2 major late promoter (Ad2 MLP) confers a more limited pattern of DNase I protection than that obtained using highly purified native hTFIID (Hahn, S., Buratowski, S., Sharp, P. A. and Guarente, L. (1989) EMBO J. 8, 3379-3382; Van Dyke, M. W., and Sawadogo, M. (1990) Mol. Cell. Biol. 10, 3415-3420; Horikoshi, M., Wang, C.K., Fujii, H., Cromlish, J.A., Weil, P.A., and Roeder, R.G. (1989) Nature 341, 299-303; Peterson, M. G., Tanese, N., Pugh, B.F., and Tjian, R. (1990) Science 248, 1625-1630; Hoey, T., Dynlacht, B. D., Peterson, M.G., Pugh, B.F., and Tjian, R. (1990) Cell 61, 1179-1186). Since the mass of the cloned TFIIDs is considerably less than that of native hTFIID (27-38 kDa versus 120-140 kDa), it is considered likely that native hTFIID exists as a mixed heterodimer. We have recently identified, purified, and characterized a novel transcription factor that binds to the CAP site region (+1 to +23) of the Ad2 MLP. This CAP site binding factor, designated CBF, is required for optimal transcriptional activity. We now show that when bound to the Ad2 MLP, yTFIID and CBF interact to generate the extended pattern of DNase I protection conferred by native hTFIID. In addition, bound yTFIID and CBF interact such that the stability of the complex exceeds that of each factor bound alone. We also demonstrate the existence in nuclear extracts of a hTFIID and CBF heterodimer by the electrophoretic mobility shift analysis. CBF, therefore, may represent the first identified member of a large family of gene-specific TFIID-associated factors that are required for the regulated gene-specific expression of TFIID activity.
The purpose of this study was to determine the overall reliability, inter-rater reliability, and criterion validity of the structured oral examination (SOE) for assessing surgical residents. An SOE consisting of four predetermined clinically oriented scenarios was administered to 23 second postgraduate year surgical residents. Each scenario had five to six questions, each with a specific marking scheme. Candidates were assessed by two examiners and scores were derived independently. Overall reliability (Cronbach's alpha) was 0.75. Inter-rater reliability was significant for each pair of examiners and each question (r = 0.78 to 0.91: p less than 0.0001). Criterion validity was measured by correlating SOE scores with multiple-choice examination (MCQ) and objective structured clinical examination (OSCE) scores. Correlations between the SOE and MCQ and OSCE were significant and fell into the moderate range (0.48 to 0.51). The results of this study show that the SOE is useful in the assessment of clinical knowledge and problem-solving abilities of the surgical resident. Overall and inter-rater reliabilities achieved exceed those of traditional oral examination formats.
To determine the respective part of modifications of glucose appearance and disappearance rates in the hypoglycemic action of a compound (B 827-33) inhibiting carnitine palmitoyl transferase (CPT I), we measured glucose kinetics ([6,6(2)H2]glucose) in normal and diabetic (streptozocin) rats before and after injection of either saline or B 827-33. Studies were initiated 4 hours (postabsorptive groups) and 24 hours (fasted groups) after food withdrawal. In all groups, there was evidence of inhibition of fatty acids oxidation (sharp decrease of ketone bodies [KB] and increase of plasma nonesterified fatty acids [NEFA]) after B 827-33 injection. Glucose levels decreased also in all groups after B 827-33 administration, the decrease being more important in starved than in postabsorptive groups and, whatever the nutritional status, in diabetic than in normal rats. In all groups, the evolution of plasma insulin was comparable after saline or B 827-33 injection. The mechanisms responsible for the decrease in glucose levels appeared dependent on the nutritional status. In postabsorptive normal and diabetic rats, compared with saline-injected rats, we observed a moderate inhibitory action (P less than .05) of B 827-33 on glucose production without stimulation of glucose utilization rate. After 24 hours of starvation, the decrease in glucose levels of normal rats was entirely due to a stimulation of glucose utilization (P less than .05), whereas glucose production was unexpectedly increased (P less than .05) above values of saline-injected rats.(ABSTRACT TRUNCATED AT 250 WORDS)
To determine the effect of insulin and glucagon on the transformation of nonesterified fatty acids (NEFA) into ketone bodies (KB), we measured simultaneously in normal subjects NEFA and KB kinetics at different NEFA levels in the presence of basal (control test) or increasing insulin concentrations with glucagopenia (somatostatin + insulin infusion, insulin test) and without glucagopenia (somatostatin + insulin + glucagon infusion, glucagon test). NEFA levels were controlled during these tests by an intravenous (IV) infusion of a triglyceride emulsion. During the control test, a moderate increase of NEFA (464 +/- 30 to 715 +/- 56 mumol/L) increased the percentage of NEFA converted into KB (13.3% +/- 1.4% to 26.4% +/- 2.1%, P less than .05), and there was a linear relationship between this percentage and NEFA levels (r = .788, P less than .01). During the insulin and glucagon tests, the progressive increase in NEFA induced by the triglyceride emulsion infusion was associated, despite the increase of insulinemia, with an increase in KB production rate (P less than .05) and in the proportion of NEFA used for ketogenesis in the presence (8.1% +/- 1.2% to 14.2% +/- 6.3%, P less than .05) and absence (15.7% +/- 2.8% to 25.2% +/- 3.99%, P less than 0.05) of glucagopenia. In both tests, this percentage was always linearly related with NEFA levels (P less than .05) and the slopes of these relationships were comparable to that observed in the control test. However, the fraction of NEFA used for ketogenesis was always higher (P less than .05) during glucagon substitution than in its absence.(ABSTRACT TRUNCATED AT 250 WORDS)
Fifteen schizophrenic patients (diagnosed according to DSM-III-R) and 15 age- and education-matched controls were tested on a computerized version of the Wisconsin card-sorting test (WCST). Slow Cortical Potentials (SCPs) were recorded throughout the performance from frontal, central and parietal electrode sites. As expected, the patients were impaired on the WCST, achieving fewer categories overall and incurring significantly more "unique" errors, although they were not significantly more perseverative than the controls. The patients did not display a generalized impairment in SCPs, differences between the groups emerging only before presentation of the key-cards and after presentation of the feedback regarding the correctness of the response. Neither the choice-card at the beginning of the trial, nor the presentation of the key-cards resulted in attenuated Evoked Potentials (EPs) in the patients. The lack of any abnormality in EPs suggests that the reason for the poor performances of schizophrenic patients on the WCST lies elsewhere than in perceptual stimulus processing. Contrary to expectations no specific impairment in frontal SCPs was detected.
The design of a skin-substitute must address the need for a dermal component, as this mesenchymally-derived tissue is important in maintaining the integrity and function of skin. An in vivo study was undertaken to assess the use of two biodegradable meshes, polyglycolic acid and polyglactin-910, as carriers for cultured human fibroblasts in a living dermal replacement. The consistent vascularization and epithelialization of these grafts placed on athymic mice showed that this has potential in re-creating the dermis in a skin-substitute.
The ortho, meta, and para forms of hydroxyphenyl acetate were found to be inhibitory in the order of ortho greater than para greater than meta in three distinct biological assays: (a) insulin-dependent assimilation of glucose into lipids in intact adipocytes, (b) growth and proliferation of Nb2 rat lymphoma cells, and (c) tyrosine phosphorylation of copolymer (Glu4Tyr) under cell-free conditions. Although relatively high concentrations of o-hydroxyphenyl acetate (OHPA) were required to inhibit these processes, the inhibitor exhibited a low index of cytotoxicity and high specificity toward inhibiting tyrosine- (but not serine-) specific kinases. Cell cycle analysis of the DNA histograms in Nb2 cells revealed that exposure to OHPA did not change the initiation of the G0/G1----S transition but drastically reduced its rate and a subsequent cell proliferation. Kinetic experiments in which the inhibitor was added or withdrawn through different phases of cell cycle confirmed this conclusion. OHPA inhibition of cell growth appears to be limited to eukaryotic cells as the growth of either gram-positive or gram-negative bacteria was unaffected by the presence of the inhibitor. The study supports the following conclusions: (a) Events that are dependent on tyrosine phosphorylation are indeed essential for mammalian cell growth and proliferation. (b) Neither the initial nor intermediate events of the proliferative cascade that occur in the Nb2 cells prior to DNA synthesis are dependent on the activity of protein tyrosine kinase(s) that are inhibited by OHPA. (c) Cell growth of prokaryotic cells and yeast may lack protein tyrosine kinase activity or be less dependent on events requiring tyrosine phosphorylation. (d) Inhibition of the insulin-dependent lipogenesis is subsequent to the inhibition of insulin receptor tyrosine kinase activity.
Evaluation, the last component in the process of patient education, is the most frequently omitted step in producing informative material. Yet, it is essential that program/material evaluation be conducted to determine the impact and success or failure of the program or material. It is vital to be aware of this need and possess knowledge about types of evaluation and those areas that must be included to provide a comprehensive evaluation.
Fifty-five eyes of 51 patients with different forms of refractory glaucoma (15 aphakic, 12 neovascular, 9 postpenetrating keratoplasty, 8 congenital, 5 secondary to uveitis, 4 associated with aniridia, 1 pseudophakic, and 1 traumatic) underwent antiglaucomatous surgery using a modified 90 degrees Schocket implant. In 25 eyes (45.4%), this was the first surgical procedure. Follow-up ranged from 3 to 27 months (mean, 10.3 +/- 5.4 months). The mean preoperative intraocular pressure (IOP) was 39.5 +/- 8.6 mmHg (range, 22 to 66 mmHg). The mean postoperative IOP was 17.8 +/- 7.6 mmHg (range, 4 to 50 mmHg). Intraocular pressure remained less than 21 mmHg in 50 eyes (90.9%) during the follow-up period. In 13 of these eyes (26.0%), IOP remained under control without any medication. Complications were observed in 13 eyes (23.6%) and were successfully treated in 11 of them. Complications included iris-tube block (5.4%), vitreous-tube block (3.6%), early postoperative flat anterior chamber (1.8%), choroidal effusion (3.6%), tube exteriorization from anterior chamber (3.6%), tube displacement from silicone band (1.8%), retinal detachment (1.8%), tube-cornea touch (1.8%), vitreous hemorrhage (1.8%), infectious endophthalmitis (1.8%), and phthisis bulbi (1.8%). Modified 90 degrees Schocket implants are an effective technique in the management of refractory glaucoma.
Pharmacokinetic and imaging studies in 19 patients receiving liposome-entrapped adriamycin (L-ADM) were carried out within the framework of a Phase I clinical trial (Gabizon et al., 1989a). The formulation of L-ADM tested consisted of 0.2 microM-extruded multilamellar vesicles composed of egg phosphatidylcholine, egg-derived phosphatidyl-glycerol (PG), cholesterol, and ADM intercalated in the fluid lipid bilayer. Plasma clearance of total drug extracted from the plasma after L-ADM infusion followed a biexponential curve with a pattern similar to that reported for free ADM. The plasma concentration of drug circulating in liposome-associated from was also measured in a subgroup of seven patients. Liposome-associated drug was found to be rapidly cleared from plasma. Its ratio to non-liposome-associated drug appeared to correlate with liver reserve, with highest ratios in patients with normal liver function. Liposome clearance, as measured by the plasma concentration of PG in three patients was slower than the clearance of liposome-associated ADM, suggesting that liposomes lose part of their drug payload during circulation. To learn about the liposome organ distribution, imaging studies were carried out with 111Indium-deferoxamine labelled liposomes of the same composition. Liposomes were cleared predominantly by liver and spleen and to a lesser extent by bone marrow in seven out of nine patients. In two patients with active hepatitis and severe liver dysfunction, there was minimal liver uptake and increased spleen and bone marrow uptake. Except for one hepatoma patient, intrahepatic and extrahepatic tumours were not imaged by liposomes, suggesting that liposome uptake is restricted to cells of the reticulo-endothelial system (RES).(ABSTRACT TRUNCATED AT 250 WORDS)
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The authors determined the reliability and validity of domain-referenced scores obtained from a multiple-station clinical skills examination administered at the University of Toronto to a group of foreign medical graduates in early 1990. Issues associated with the identification of essential checklist items and the setting of minimum passing scores (cutting scores) for each station and for the total test were addressed. In addition, they examined the consistency of classification of candidates and the perceived appropriateness of the number of candidates classified "competent." The findings provide evidence of the validity of standard-setting procedures based on both the performance of criterion groups and the judgment of "experts."
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Survey data were collected from 45 states on the extent to which transfer of custody was required for families to obtain intensive services for children with serious emotional disturbances. In 28 of the states (62 percent), at least one agency serving children reported using transfer of custody as a requisite for obtaining services. Corrections and social service agencies were most likely to require transfer of custody, followed by youth services and mental health agencies. Most agencies that required transfer of custody lacked statutes or regulations governing two of the three types of transfers used. States that required transfer of custody tended to be less populated and to have a lower per capita income than states that did not. The major factor contributing to use of transfer of custody, the authors conclude, is the absence of an adequate system of services designed specifically for children with serious emotional disturbances.