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31.
    
Over a period of 4.5 years, 14 patients with frontoethmoidal meningoencephaloceles were treated. Most patients came from Northern Namibia. Precise delineation of all cranial abnormalities was obtained by modern imaging techniques, and specific patterns of cerebral abnormality were found. The malformation was corrected in a single stage, and significant modifications have been developed to render the procedure simpler and safer. Information from our series favors delayed neural tube closure as the primary pathogenesis of the defect and suggests a common teratogen as the most probable etiological agent. Our experience leads us to advocate early correction of even small defects.  相似文献   
32.
    
BACKGROUND: Little is known about the rehabilitation outcomes of long-term survivors following treatment for head and neck cancer. There are, for example, no studies on physical and psychosocial rehabilitation outcomes of T1 glottic larynx carcinoma, despite the fact that these form the majority of head and neck cancer sites. Thus, this investigation afforded a unique opportunity for examining similarities and differences among T1 glottic larynx patients, laryngectomy patients, and those who had surgery for cancer of the oral cavity and/or oropharynx along a variety of physical and psychosocial dimensions. METHODS: To describe the impact of these three types of head and neck cancer and their treatment on the physical and psychosocial functioning of long-term survivors, a self-report questionnaire was completed by 110 patients treated between 2 and 6 years previously in a major cancer center. RESULTS: Data indicate that a higher percentage of patients treated with laryngectomy or commando procedures still experience severe psychosocial distress between 2 and 6 years after their last treatment than do patients treated with radiotherapy for a T1 carcinoma of the glottic larynx. Psychosocial and physical complaints are still reported by many laryngectomy patients, apparently the result of problems in effective communication with others. Many commando procedure patients experience problems with respect to food intake, and with disfigurement and its consequences. T1 larynx patients mainly experience a considerable number of physical complaints. The greater the time that had elapsed since treatment, the fewer the psychosocial problems associated with head and neck tumors. Open discussion of the illness in the family, social support, and perceptions of adequate information from the specialist are the most important predictors of positive rehabilitation outcomes. CONCLUSIONS: This study indicates that T1 larynx patients report many physical complaints even though several years had elapsed since treatment. Also, laryngectomy patients may need psychosocial guidance for a longer posttreatment period and that health care personnel must involve the partner as much as possible in all communications. Commando procedure patients in particular feel hindered by their disfigurement and its consequences. Future research with respect to validation of the specific head and neck modules is needed.  相似文献   
33.
    
The human prion encephalopathy Creutzfeldt-Jakob disease often is manifest as rapidly progressing dementia with myoclonus and synchronous, periodic discharges. To investigate the electrophysiology of prion disease we used intra- and extra-cellular recordings from brain slices from Tg(SHaPrP+/+) 81 mice, which express Syrian hamster prion protein and which are susceptible to hamster-passaged scrapie isolates. Forty days after intracerebral inoculation with scrapie isolate Sc237, we recorded prolonged, epileptiform discharges in cortex and hippocampus. Neurological signs were subtle and histopathology was minimal. Central nervous system (CNS) dysfunction progressed; by 57 days the mice were ataxic, had spongiform histopathology and they died in <63 days. During the terminal phase, intrinsic neuronal properties changed dramatically and action potentials broadened from <4 to 20-100 ms in 30% of cortical cells. We conclude that brain dysfunction in experimental scrapie precedes clinical signs and spongiform histopathology, and is preserved in slices maintained in vitro, making it accessible to electrophysiological analysis.  相似文献   
34.
    
N-Acetyltransferase, which is suggested to be responsible for the production of N1-acetylspermidine in Leishmania amazonensis and to be involved in the process of inactivation and degradation of excessive polyamines, was partially purified and characterized. Among the substrates tested, sym-norspermidine, sym-norspermine, and 1,3-diaminopropane had the highest reaction rates, but the naturally occurring polyamines spermine and spermidine were also acetylated at considerable rates, whereas putrescine was a poor substrate. The Michaelis constants (Km values) for spermine and spermidine were 0.66 and 3.3 mM, respectively. The Km value for acetylcoenzyme A (acetyl-CoA) was determined to be 34 microM. CoA inhibited the reaction in a competitive manner; the inhibition constant was 5 microM. The enzyme showed an apparent relative molecular mass of 35,000.  相似文献   
35.
36.
    
G292 osteoblastic cells were cultured in dishes made with a flexible base of polytetrafluoroethylene (PTFE) and stretched ( approximately 1% strain level) continuously for 48 hours. Patch-clamp recording techniques were then used to monitor single channel currents of mechanosensitive ion channels in these cells. To stimulate mechanosensitive channels, we applied suction to the membrane, expressed as -cm Hg, directly through the patch pipette. GigaOhm seals were obtained on a total of 33 osteoblasts that contained a high-conductance ( approximately 180 pS) mechanosensitive channel, all in the cell attached configuration. Of these, 18 were obtained from cells that had been stretched for either 1 (n = 6), 24 (n = 4), or 48 (n = 8) hours, and 15 were obtained in control (nonstretched) cells at either 1 (n = 2), 24 (n = 5), or 48 (n = 8) hours. For unstrained cells, applied pressures ranging from -1 to -5 cm Hg increased the probability of channel opening (Popen) from 0.05 +/- 0. 01 (mean + SEM) to 0.12 +/- 0.07. By contrast, for the same values of applied pressure in stretched cells, Popen ranged from 0.06 +/- 0. 01 to 0.49 +/- 0.15. Our results suggest that intrinsic properties of mechanosensitive ion channels in the G292 osteoblastic cell may be modulated by continuous mechanical loading of the cell itself.  相似文献   
37.
    
Intravenous heparin is routinely given after thrombolytic therapy for patients with acute myocardial infarction in the United States and in some, but by no means all, other countries. Several trials have documented improved infarct-artery patency in patients treated with heparin; however, none was large enough individually to assess the effect of heparin on clinical outcomes. We performed a systematic overview of the 6 randomized controlled trials (1,735 patients) to summarize the available data concerning the risks and benefits of intravenous heparin versus no heparin after thrombolytic therapy. Mortality before hospital discharge was 5.1% for patients allocated to intravenous heparin compared with 5.6% for controls (relative risk reduction of 9%, odds ratio 0.91, 95% confidence interval 0.59 to 1.39). Similar rates of recurrent ischemia and reinfarction were observed among those allocated to heparin therapy or control. The rates of total stroke, intracranial hemorrhage, and severe bleeding were similar in patients allocated to heparin; however, the risk of any severity of bleeding was significantly higher (22.7% vs 16.2%; odds ratio 1.55, 95% confidence interval 1.21 to 1.98). There was no significant difference in the observed effects of heparin between patients receiving tissue-type plasminogen activator and those receiving streptokinase or anisoylated plasminogen streptokinase activator complex, or between patients who did and did not receive aspirin. The findings of this overview demonstrate that insufficient clinical outcome data are available to support or to refute the routine use of intravenous heparin therapy after thrombolysis. It is not known if these findings are due to lack of statistical power, inappropriate levels of anticoagulation, or lack of benefit of intravenous heparin. Large randomized studies of heparin (and of new antithrombotic regimens) are needed to establish the role of such therapy.  相似文献   
38.
    
It has been previously reported that Bryostatin 1 (Bryo1) induces differentiation of the human acute lymphoblastic leukemia (ALL) cell line, Reh, to a monocytoid B-cell stage. In this study we demonstrate that a novel protein, ubiquitin COOH-terminal hydrolase (UCH-L1), is associated with this differentiation. Reh cells were treated with 200 nmol/l of Bryo1 for 72 h and analyzed for changes in morphology, surface immunophenotype, acid phosphatase and terminal deoxynucleotidyl transferase. Protein patterns of the parent and differentiated cells, by two-dimensional polyacrylamide gel electrophoresis (2D PAGE), were studied. Bryo1-treated cells expressed morphologic, phenotypic and enzymatic features of the monocytoid B-cell stage. The UCH-L1 enzyme (MW-pl 34-5.3) was detected by 2 D PAGE in the differentiated, but not in parent cells. The presence of UCH-L1 in the Bryo1-treated cells was further confirmed by immunoblotting of 2 D PAGE using UCH-L1 polyclonal antibody. Ubiquitin expression was studied in parent and Bryo1-treated cells and was compared with 12-O-tetradecanoylphorbol-13-acetate (TPA)-treated cells. Both agents, TPA and Bryo1, increased the level of ubiquitin expression as detected by flow cytometry. Sodium borohydride, an inhibitor of UCH-L1, inhibited the Bryo1-induced differentiating effect on Reh cells. To date, the mechanism by which Bryo1, exerts its B-cell differentiating effect is not fully understood. This study shows that UCH-L1 expression may play a major role in Bryo1-induced differentiation in pre-B-ALL.  相似文献   
39.
    
The renal uptake of radiolabeled antibody fragments and peptides presents a problem in radioimmunodetection and therapy, compromising lesion sensitivity, especially with intracellularly-retained isotopes. Previously, we showed that cationic amino acids and their derivatives are capable of significantly reducing kidney uptake in animals. We report our initial clinical results of successful renal uptake reduction in five patients who underwent cancer radioimmunodetection with 99mTc-anti-CEA Fab' fragments. METHODS: The patients were infused with two liters of a commercially-available nutritive amino acid solution (containing approximately 2.25 g/liter lysine-glutamate and 2.50 g/liter arginine), whereas 75 control patients received the same volume of saline (quantification of organ and tumor kinetics from conjugate whole-body views by ROI technique). RESULTS: The renal uptake in the amino acid group was significantly lower (p<0.05) than in the control group (11.1 +/- 2.0% injected dose versus 17.7 +/- 7.0% injected dose at 24 hr postinjection), whereas the uptake of all other organs remained unaffected. Gel filtration chromatography of the urine taken from amino-acid-treated patients showed that a significantly higher amount of excreted activity was bound to intact Fab' (53% of excreted activity) in contrast to only less than 10% in the control group. CONCLUSION: The renal uptake of monoclonal antibody fragments in patients can be reduced significantly by amino acid infusion, even at considerably lower doses than those that were safe and effective in animals. As was found in animals, the mechanism seems to rely on an inhibition of the re-absorption of tubularly-filtered proteins by the proximal tubule cells. These results encourage further clinical trials to lower the renal uptake experienced in radioimmunodetection, as well as in therapeutic trials with antibody fragments and peptides.  相似文献   
40.
    
Over a period of 10 years 17 human immunodeficiency virus(HIV)-infected patients with laryngeal Kaposi's sarcoma were seen and treated at University College London Hospitals. All patients had advanced HIV disease. Their presentation was with symptoms of upper airway obstruction in the majority of cases and the diagnosis was made by fibreoptic examination of the larynx. Biopsy was associated with brisk haemorrhage in one patient, who required a temporary tracheostomy, and was not performed in the other 16 cases. The commonest site of laryngeal involvement was the supraglottis in 11 patients, with glottic lesions noted in eight patients: subglottic lesions were seen in only three. Treatment of laryngeal Kaposi's sarcoma was, in general, conservative, five patients received low dose radiotherapy to the larynx and 10 were treated with systemic chemotherapy for disseminated Kaposi's sarcoma. Laryngeal Kaposi's sarcoma did not contribute to patient mortality.  相似文献   
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