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41.
    
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   
42.
    
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   
43.
44.
    
Absorbable stapling devices have been described by several groups for the creation of continent urinary diversions. Experience with these devices in the creation of the LeBag ileocecal orthotopic pouch is described. Use of the staplers simplifies pouch construction and yields functional results similar to hand-sewn reservoirs.  相似文献   
45.
    
Scleroderma (SSc) is a disease characterized by skin fibrosis but it is the end-organ effect of microvascular injury and fibrosis that is important prognostically. Pulmonary involvement in SSc patients, either of parenchymal fibrosis and/or pulmonary hypertension, is a major cause of morbidity and mortality. Interstitial lung disease occurs more commonly in patients with diffuse SSc and is associated with a loss of lung volume, as well as a defect of gas exchange. Parenchymal fibrosis may also cause pulmonary hypertension. Isolated pulmonary hypertension occurs exclusively in patients with limited SSc and is detectable by a reduced DCO. The early identification of either manifestation is difficult. Patients may have minimal symptoms, unremarkable physical findings, normal chest radiographs and/or minimally abnormal pulmonary function tests at a time when significant lung pathology is present. It is essential to attempt to identify pulmonary disease early, at a potentially reversible stage. Multiple therapeutic endeavours have yielded only short-term or minimal benefits in symptoms and pulmonary function, and thus a major alteration in SSc pulmonary prognosis has not been achieved. Further study of the pathogenesis of this disease manifestation will be helpful in its earlier identification and intervention.  相似文献   
46.
    
The influence of noncompetitive (MK-801), competitive (AP-7) and the antagonist of polyamines site of NMDA receptor (arcaine) on the central activity of angiotensin II (A II) was studied. The open field test, conditioning of active avoidance responses (CARs) and passive avoidance situation was used to investigate learning and memory in rats. All used antagonists decreased beneficial action of A II on these processes.  相似文献   
47.
    
We have implemented an iterative algorithm for the identification of diagnostic patterns from sets of multiple-domain proteins, where domains need not be common to all the proteins in the defining set. Our algorithm was applied to sequences gathered using a variety of methods, including BLAST, common keywords, and common E.C. numbers. In all cases, useful diagnostic patterns were obtained, possessing both high sensitivity and specificity. The patterns were found to correlate in several cases with both functional and structural domains. Patterns generated from a large number of sequence families were analyzed for probable multiple-domain structure.  相似文献   
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49.
Elevated thoracic temperature increases the wingbeat frequency of flying locusts. We investigated the extent to which temperature-induced changes in resting membrane potential and postsynaptic potential amplitude contribute to the effects of increased temperature on the frequency of the central flight rhythm. Flight neurons were hyperpolarized by changing the K+ concentration of the superfusing saline from 10 mM to 2 mM. 5 min of low-K+ superfusion hyperpolarized flight motoneurons from -42.8 mV to -50.1 mV with a concomitant decrease of the frequency of the central flight rhythm from 11.6 Hz to 10.5 Hz. The amplitude of postsynaptic potentials was halved after 10 min of zero Ca2+/high Mg2+ superfusion, but the frequency of the central rhythm did not change significantly. GABAergic inhibitory connections were reduced in amplitude using picrotoxin. This treatment increased the frequency of the central rhythm from 11.6 Hz to 12.9 Hz, and increased the thermosensitivity of the rhythm frequency. We conclude that the excitatory effect of increased temperature on rhythm frequency is not mediated by temperature effects on membrane potential and/or synaptic potential amplitude. We propose that the inhibitory effect of temperature-induced hyperpolarization of the membrane potential compensates for the excitatory effect of temperature on rhythm frequency (e.g. via increased conduction velocity). We further suggest that some measure of temperature compensation is afforded by equal effects on the amplitudes of excitatory and inhibitory postsynaptic potentials, such that the net effect on the level of excitation is zero.  相似文献   
50.
The course of two neonates and one 4-month-old infant with laboratory and clinical evidence of central hypothyroidism is described. All three presented with failure to thrive and improved after L-T4 therapy. Early recognition and treatment of newborns and infants with central hypothyroidism is important to maximize the potential for growth and development. Two of the three infants have been documented to have transient central hypothyroidism of hypothalamic origin, not previously reported.  相似文献   
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