Cancer treatment monitoring with fluorine-18 2-fluoro-2-deoxy-D-glucose and positron emission tomography: frustration or future.
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Animals↗
Biomedical subjects
R Paul
Publications and source records attributed to R Paul.
Phonological behavior in toddlers with slow expressive language development.
Toddlers with slow expressive language development were compared to normally speaking age-mates on three global measures of phonological behavior: the average level of complexity of their syllable structures, the number of different consonant phonemes produced, and the percentage of consonants correctly produced in intelligible utterances. The groups were found to differ significantly on all three variables. Further analyses were done, breaking the groups down into narrower age ranges. These comparisons also revealed differences between late-talking and normal youngsters. Detailed analyses of the range of phonemes and syllable structures produced, as well as the appearance of phoneme classes within syllable structures and positions, revealed that late talkers showed a delayed rather than a deviant pattern of phonological development. The implications of these findings for identifying and monitoring expressive delay in toddlers are discussed.
Articulation Disorders↗
Role of the PU.1 transcription factor in controlling differentiation of Friend erythroleukemia cells.
Both viral and cellular genes have been directly implicated in pathogenesis of Friend viral erythroleukemia. The virus-encoded gp55 glycoprotein binds to erythropoietin receptors to cause mitogenesis and differentiation of erythroblasts. However, if the provirus integrates adjacent to the gene for the PU.1 transcription factor, the cell loses its commitment to terminally differentiate and becomes immortal, as indicated by its transplantability and by its potential for indefinite growth in culture (C. Spiro, B. Gliniak, and D. Kabat, J. Virol. 63:4434-4437, 1989; R. Paul, S. Schuetze, S. L. Kozak, and D. Kabat, J. Virol. 65:464-467, 1991). To test the implications of these results, we produced polyclonal antiserum to bacterially synthesized PU.1, and we used it to analyze PU.1 expression throughout leukemic progression and during chemically induced differentiation of Friend erythroleukemia (F-MEL) cell lines. This antiserum identified three electrophoretically distinct PU.1 components in extracts of F-MEL cells and demonstrated their nuclear localization. Although PU.1 proteins are abundant in F-MEL cells, they are absent or present in only trace amounts in normal erythroblasts or in differentiating erythroblasts from the preleukemic stage of Friend disease. Furthermore, chemicals (dimethyl sulfoxide or N,N'-hexamethylenebisacetamide) that overcome the blocked differentiation of F-MEL cells induce rapid declines of PU.1 mRNA and PU.1 proteins. The elimination of PU.1 proteins coincides with recommitment to the program of erythroid differentiation and with loss of immortality. These results support the hypothesis that PU.1 interferes with the commitment of erythroblasts to differentiate and that chemicals that reduce PU.1 expression reinstate the erythropoietic program.
Animals↗
Colour Doppler ultrasound in the management of a case of cranial arteritis.
Colour Doppler ultrasound allows simultaneous B scan and Doppler imaging and can be employed to determine the velocity of blood flow in the vasculature of the eye and orbit. We describe a case of cranial arteritis (giant cell arteritis) in which serial velocimetry recordings were obtained. At one stage in the disease process no blood flow was detectable in the orbit despite previously reliable recordings. This coincided with a deterioration of the clinical state of the patient as signified by recurrent anterior ischaemic optic neuropathy despite controlled symptomatology and erythrocyte sedimentation rate by prednisolone therapy. Subsequent increase in the immunosuppressive therapy was accompanied by a return of blood flow in the orbit. Colour Doppler ultrasound may prove to be a useful examination technique in the diagnosis and management of cranial arteritis.
Aged↗
[Hematological isotope studies].
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Anemia↗
Venous thrombosis: a controlled study on the performance of scintigraphy with 99Tcm-HMPAO-labelled platelets versus venography.
Thirty-three patients with symptoms and signs of a deep venous thrombosis (DVT) were examined by contrast venography and radionuclide imaging with 99Tcm-hexamethylpropyleneamineoxime (99Tcm-HMPAO)-labelled autologous platelets. There were 13 patients on heparin therapy and 20 without anticoagulation during the scintigraphy. Scintigraphy consisted of blood pool imaging at 5 to 20 min and accumulation imaging at 2, 4-6 and 18-24 h. In scintigraphy a positive finding was either a defect of radioactivity in the immediate blood pool phase or a hot spot indicative of accumulation of platelets in later phases. Fifteen out of 23 patients positive by venography were also positive by scintigraphy. Five of the eight false negative patients were on heparin treatment, two probably had DVT which were not quite fresh. The venography negative patients were also negative on scintigraphy. Nine out of 12 patients without anticoagulation had positive platelet accumulation compared with two out of 11 patients on heparin therapy. This difference was statistically significant (P less than 0.025). The sensitivity and specificity of platelet scintigraphy were 65 and 100%, respectively, in all patients and 83 and 100% in patients without anticoagulation. Our results suggest that scintigraphy with 99Tcm-HMPAO-labelled platelets is a useful alternative in diagnosing DVT in patients in whom a standard contrast X-ray venograph is contraindicated or otherwise unsuccessful.
Adult↗
The role of selection bias in comparing cesarean birth rates between physician and midwifery management.
OBJECTIVE: The midwifery service at our hospital has been observed to have a 2% cesarean birth rate consistently over a 10-year period. There are substantial differences in labor management style between the midwives and physicians. We sought to test the hypothesis that the low cesarean birth rate on the midwifery service was the result of patient selection bias. METHODS: A randomized blinded clinical trial was conducted in which 492 low-risk patients were assigned to either physician or midwifery management. The provider responsible for labor management was unable to determine group assignment. Patients in the midwifery group were managed by previously established protocols, and outcome was attributed to the midwives even if the patients subsequently required transfer to physician management. Route of delivery was the primary outcome measurement. Continuous variables were analyzed using Student t test and discrete variables using chi 2. RESULTS: There were no demographic differences between the groups, and the admission pelvic examinations were the same. The patients assigned to the midwifery group had a 2.1% cesarean birth rate, whereas those assigned to physician management had a 0.4% rate. The higher rate of operative vaginal deliveries in the physician group was statistically significant. There were no differences in neonatal outcomes. The physician-managed group had significantly more episiotomies and third- and fourth-degree extensions. CONCLUSIONS: The 2% cesarean birth rate observed on the midwifery service appeared to be the result of patient selection bias. A low cesarean birth rate can be achieved by either physician or midwifery management in a selected low-risk population.
Adult↗
Neuronal activity in narcolepsy: identification of cataplexy-related cells in the medial medulla.
Narcolepsy is a neurological disorder characterized by sleepiness and episodes of cataplexy. Cataplexy is an abrupt loss of muscle tone, most often triggered by sudden, strong emotions. A subset of cells in the medial medulla of the narcoleptic dog discharged at high rates only in cataplexy and rapid eye movement (REM) sleep. These cells were noncholinergic and were localized to ventromedial and caudal portions of the nucleus magnocellularis. The localization and discharge pattern of these cells indicate that cataplexy results from a triggering in waking of the neurons responsible for the suppression of muscle tone in REM sleep. However, most medullary cells were inactive during cataplexy but were active during REM sleep. These data demonstrate that cataplexy is a distinct behavioral state, differing from other sleep and waking states in its pattern of brainstem neuronal activity.
Animals↗
Rapid diagnosis of epidemic nephritis caused by hantavirus.
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Hemorrhagic Fever with Renal Syndrome↗
The theory of the frequency response of ellipsoidal biological cells in rotating electrical fields.
In this paper we have presented in as compact a form as possible the theoretical formalism that is needed to predict the frequency response of a biological cell of arbitrary ellipsoidal shape to a frequency dependant rotating external field. The formalism is much more complicated than that for a spherical or cylindrical cell where the radial vector is always parallel to the surface normal at each point of the surface. In addition to providing the theory we have demonstrated that the spin rate and its frequency dependance is very intimately related to the electrical properties of the cell interior and to that of the suspending fluid. It is possible to probe these properties of the cell and its environment by utilizing this technique. This aspect has been demonstrated by examining rotational changes as a function of the conductivity of both the cell interior and its suspending liquid. We also have shown, by considering a very simple model for the cell and the two dielectric constants, that the frequency spectrum is shape dependant. All our calculations have been carried out for "lossy" systems with frictional dissipation where energy minimization methods are no longer applicable. The invariant form of the Poynting vector forms the basis of the method.
Animals↗
Additional mapping of mouse chromosome 2 genes.
The purpose of this work was to elucidate the genetic fine structure of the central portion of mouse chromosome (Chr) 2. Seven Chr 2 congenic mouse strains [B10.PA(L)-pa we un at, B10.PA(L)-pa Aw, B10.PA(L)-we un at, B10.PA(J)-pa a, B10.FS-we Aw, B10.C-we Aw, and B10.YBR-a] were produced. Breeding studies were carried out using strains B10.PA(L)-pa we un at and B10.LP-H-13b to accurately determine the recombination frequencies between marker genes pa and we (1.9% +/- 0.3), we and un (8.8% +/- 0.5), and un and at (4.5% +/- 0.4) of strain B10.PA(L)-pa we un at. These strains and other Chr 2 congenic strains were typed for immunologically defined loci using monoclonal antibody (mAb) C23 reactive with the gene product of B2mb T-lymphocyte clone C1 reactive with the gene product of H-3a and H-3c, and lymphocyte clone H1.8 reactive with the gene product of Hd-1a. B2m and H-3 typing located a recombinational event separating [pa B2m H-3] from we (the order of bracketed genes is not known). Hd-1 typing indicated that Hd-1 maps distal to [H-42, H-44] and proximal to un. The gene order [pa, B2m, H-3], we, [H-42, H-45], Hd-1, un, H-13, at, with H-44 mapping centromeric to Hd-1, is indicated by the data.
Animals↗
The "whisker sign" as an indicator of ochronosis in skeletal scintigraphy.
A patient with alkaptonuria and ochronotic arthrosis was imaged twice with technetium-99m dicarboxypropane diphosphonate (99mTc-DPD)--once during a bout of arthritic knee pain and once when symptom-free. There was a marked accumulation of radioactivity in the large joints. During the episode of arthritis the knee joints had a higher uptake than when the patient was without symptoms. The intervertebral discs showed a high uptake which extended laterally from the axial vertebral column; the finding gave an impression of whiskers, and this "whisker sign" may be characteristic of ochronosis.
Alkaptonuria↗
Determination of 2-fluoro-2-deoxy-D-glucose uptake and ATP level for evaluating drug effects in neoplastic cells.
The glucose analogue 2-fluoro-2-deoxy-D-glucose (FDG) was used to study chemosensitivity of two human ovarian cancer cell lines and of murine L1210 cells. Cell viability was determined by measuring intracellular adenosine triphosphate (ATP) with a bioluminescence method, which has been shown to correlate closely with trypan blue, stem cell, and [3H]TdR assays. All three cell lines were sensitive to cytostatic drugs, which exerted a parallel decrease in the intracellular FDG and ATP levels. The two measures correlated positively (r = 0.66, P less than 0.001), indicating that FDG uptake is closely linked with ATP production. Relatively low hexokinase (HK)-to-glucose 6-phosphatase (HK/G6-Pase) ratios were measured, which suggests that the metabolic trapping of FDG 6-phosphate within the cytosol is incomplete. Apparently, these cell lines may not depend exclusively on glycolysis for their energy requirement. We conclude that cell killing caused by cytostatic drugs is associated with a decreased ATP content and FDG uptake. This indicates that not only ATP but also FDG may be used to study drug effects in vitro.
Adenosine Triphosphate↗
Radiation effects on uptake of 99Tcm-hexamethylpropylen amine oxime (HMPAO) in head and neck tumours.
Twenty patients with malignant head and neck tumours were imaged with 99Tcm-labelled hexamethylpropylene amine oxime (HMPAO), a radiopharmaceutical generally used for blood flow studies. Before radiotherapy (RT), 93% of the tumours could be detected with single photon emission computed tomography (SPECT) and 45% with planar imaging. Whole tumour-to-background 99TcmHMPAO uptake ratios ranged from 3.6 to 1.0 (mean 1.7 +/- 0.6) in untreated tumours. There was a good correlation between tumour volume and uptake (r = 0.69, P = 0.002). Sixteen patients were reimaged during or shortly after radical RT. 99TcmHMPAO uptake was significantly lower after treatment (mean uptake ratio 1.2 +/- 0.3, P less than 0.001). However, RT associated changes in 99TcmHMPAO uptake were in agreement with the clinical response in only 63% of the studies. This study indicates that 99TcmHMPAO SPECT imaging can be used for pretherapeutic localisation of head and neck tumours. Although most tumours show a decrease in uptake after irradiation the poor association with tumour regression does not allow for reliable assessment of treatment response.
Adult↗
Communication and socialization skills at ages 2 and 3 in "late-talking" young children.
Twenty-one apparently normal children between 18 and 34 months of age with slow expressive language acquisition were compared to a group of normally speaking children matched for age, SES, and sex ratio, on the Vineland Adaptive Behavior Scales (Sparrow, Balla, & Cicchetti, 1984). The late talkers (LTs) scored significantly lower not only in expressive communication, but also in receptive communication and socialization. A follow-up study of the same subjects, seen at age 3, showed nearly half the 3-year-olds with a history of LT remained delayed in expressive communication and socialization, while one third remained behind in receptive language. The data suggest that social skills are particularly vulnerable to disruption in children with late expressive language development, even after communication skills have moved into the normal range. They suggest, further, that receptive deficits do not seem, in themselves, to increase the risk of continued language delay. Clinical implications of these findings are discussed.
Child Language↗
Maternal linguistic input to toddlers with slow expressive language development.
Maternal speech styles to children between 20 and 34 months of age who were slow to acquire expressive language were compared to those of mothers with normally speaking toddlers. Aspects of the mothers' speech examined included use of various sentence types (declaratives, negative, questions, etc.); the mother's lexical contingency with regard to the child's utterance; mother's use of pragmatic functions such as requests, comments, and conversational devices; and the mother's use of topic management. Results revealed that mothers of toddlers with slow language development are different from mothers of normal speakers only in their frequency of use of lexical contingency devices, specifically, expansion and extension. However, the proportion of expansions and extensions relative to the number of child utterances is not different, indicating that when late talkers give their mothers something to expand, the mothers do so, but that the late talkers do not give their mothers as much speech to work with as do the normal toddlers. Implications of these findings for parent training are discussed.
Child, Preschool↗
[99Tcm]MAG3 gamma camera nephrography in epidemic nephritis.
There is a lack of systematic nephrographic studies on epidemic nephritis (EN). We studied 10 patients with EN using [99Tcm]MAG3 gamma camera nephrography and followed up 9 of them 22-68 days later when they had clinically recovered. Variables for renal clearance of [99Tcm]MAG3 and the retention of radioactivity in the kidneys and blood were calculated. In all patients renal function was impaired acutely. There was marked reconstitution of renal function in the control studies. [99Tcm]MAG3 clearance was inversely related to serum creatinine. On visual inspection the nephrograms showed no focal changes. Nephrography was more sensitive than sonography at identifying renal impairment. [99Tcm]MAG3 nephrography is a sensitive method for identifying renal involvement and reconstitution of renal function in EN. It may be a valuable adjunct to the diagnostic arsenal, especially in nonendemic areas where EN occurs only sporadically and where there may be diagnostic uncertainty in patients presenting acutely with EN.
Disease Outbreaks↗
The Sfpi-1 proviral integration site of Friend erythroleukemia encodes the ets-related transcription factor Pu.1.
Previous studies identified a common site (Sfpi-1) for proviral integration in immortalized Friend erythroleukemias. cDNAs corresponding to a 1.5-kb Sfpi-1 mRNA were isolated and sequenced. These were larger than an independently isolated Sfpi-1 cDNA described by researchers from another laboratory, and they contained common differences from that sequence, including in the coding region four extra nucleotides that altered the reading frame. The properly translated protein is identical to Pu.1, a transcription activation factor that is related to the ets oncogene family. Genetic methods were used to map Sfpi-1 with respect to other loci on mouse chromosome 2. Our results suggest that Pu.1 blocks erythroblast differentiation and thereby causes immortalization.
Amino Acid Sequence↗