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71.
Efficacy of a replication-competent adenovirus (ONYX-015) following intratumoral injection: intratumoral spread and distribution effects 总被引:8,自引:0,他引:8
ONYX-015 is an E1B-deleted adenovirus that replicates in and causes lysis of p53-deficient cancer cells selectively. To study the efficiency of intratumoral (i.t.) spread by ONYX-015, we infected specific fractions of tumor cells (two p53-deficient tumor lines and one p53 functional line) in vitro before subcutaneous inoculation into nude mice. Infection of as few as 5% of p53- tumor cells prevented tumor development in all cases; infection of 1% of p53- tumor cells resulted in significant growth inhibition but did not prevent tumor formation. In contrast, infection with ONYX-015 had no significant effect on p53+ tumor formation. These data suggested that replication-dependent tumor cell lysis and spread was occurring, but that tumor destruction might be improved by increasing i.t. virus distribution. Two treatment parameters were then varied to determine whether virus distribution, and consequently efficacy, could be improved. Divided i.t. injections of virus were more efficacious than a single injection of the same total dose. Likewise, increasing the volume of the viral suspension for i.t. injection allowed better distribution within the tumor mass and increased efficacy. These results have implications for the treatment of cancer patients with viral agents. 相似文献
72.
Low birthweight infants aged 4-41 days were given from birth one of three experimental milk formulae varying widely in content of calcium and phosphate. Ca and P in feed, urine, and faeces were measured between carmine markers corresponding to a metabolic period of 48 hours. Calcium enriched in 46Ca to provide a marker for the dietary Ca was added to one feed and 46Ca measured in urine and faeces. True absorption of Ca and endogenous excretion into the bowel could then be inferred. True absorption of Ca was proportional to Ca intake and independent of P intake. Endogenous faecal excretion seemed to be independent of both Ca P intakes, and varied widely between different infants in the range 4-150 mg/day. Urine Ca was low and retention was essentially the difference between true absorption and endogenous faecal excretion. Retention of Ca tended to be much greater on a high Ca intake, but the variability in retention between infants on a given intake was large, paralleling the variability in endogenous faecal excretion. The variability in plasma Ca concentrations in newborn infants may in part be a consequence of wide individual variability in endogenous faecal excretion. The 46Ca marker technique provides a means of investigating the factors determining this variability. 相似文献
73.
DP Southall WA Arrowsmith JR Oakley G McEnery RH Anderson EA Shinebourne 《Archives of disease in childhood》1979,54(10):776-779
Two neonates with arrhythmias and the long QT syndrome are described. The arrhythmias were detected in utero and both infants were apparently well after birth. The first infant, although well, had a bradycardia for the first 9 days of life. A normal heart rate was documented at 10 days but a prolonged QT interval was not appreciated on the ECG. He was discharged from hospital but died suddenly and unexpectedly 3 days later. A post-mortem examination failed to find a cause for his death which therefore fell into the category of the sudden infant death syndrome (SIDS). A retrospective analysis of the perinatal electrocardiogram showed a probable junctional rhythm with 2:1 conduction to the ventricle; the QT interval was prolonged at 0.52 seconds (QTC = 0.63). The second infant had a QT interval of 0.52 seconds (QTC = 0.54) and frequent ventricular premature beats on a 24-hour electrocardiogram. She was treated with propranolol and remains well 2 years later. Sudden infant death has often been described in the siblings of children with the long QT syndrome and one other report described a case of SIDS which was said to have had a prolonged QT interval on the perinatal ECG. This report, however, provides unquestionable evidence, in one case, of an association between the long QT syndrome and SIDS. 相似文献
74.
S. Arnolds B. Kuglin C. Kapitza T. Heise 《International journal of clinical practice》2010,64(10):1415-1424
This pedagogical review illustrates the differences between pharmacokinetic (PK) and pharmacodynamic (PD) measures, using insulin therapy as the primary example. The main conclusion is that PD parameters are of greater clinical significance for insulin therapy than PK parameters. The glucose‐clamp technique, the optimal method for determining insulin PD, is explained so that the reader can understand the important studies in the literature. Key glucose‐clamp studies that compare two basal insulin analogues – insulin glargine and insulin detemir – to Neutral Protamine Hagedorn insulin and to each other are then presented. The review further explains how PD parameters have been translated into useful clinical concepts and simple titration algorithms for everyday clinical practice. Finally, the necessity of overcoming patient and/or physician barriers to insulin therapy and providing continuing education and training is emphasised. 相似文献
75.
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77.
Clifford S. Cho Merril T. Dayton Jon S. Thompson Walter A. Koltun Charles P. Heise Bruce A. Harms 《Journal of gastrointestinal surgery》2008,12(7):1221-1226
Background The association between primary sclerosing cholangitis (PSC) and ulcerative colitis (UC) often mandates their contemporaneous
management. Orthotopic liver transplantation (OLTX) has emerged as the only curative therapy for PSC, and total proctocolectomy
with ileal pouch-anal anastomosis (IPAA) is the definitive treatment for refractory UC. The published experience to date describing
IPAA after OLTX has been limited; we sought to examine outcomes associated with proctocolectomy-IPAA after OLTX.
Materials and Methods We reviewed our multi-institutional experience performing proctocolectomy-IPAA for UC after OLTX for PSC.
Results Twenty-two patients underwent proctocolectomy-IPAA for UC after OLTX for PSC at four academic medical centers between 1989
and 2006. No perioperative complications or allograft dysfunction were observed. During a median follow-up of 52 months, complications
have included transient dehydration (n = 6), chronic pouchitis (n = 2), recurrent PSC (n = 2), small bowel obstruction (n = 2), and pouch-anal anastomotic stricture (n = 1). Median 24-h stool frequency was 5, and fecal continence was reported as satisfactory by all patients.
Conclusions This multi-institutional experience suggests that proctocolectomy-IPAA can be performed safely after OLTX. Management strategies
should include optimization of small bowel length during pouch and ileostomy construction, vigorous postoperative hydration,
early ileostomy closure, and careful monitoring for pouchitis. 相似文献
78.
At birth, premature infants of 25-29 weeks gestation, at high risk for development of neonatal respiratory distress syndrome (RDS), were given a single dose (90 mg) of calf lung surfactant extract (CLSE) by intratracheal instillation. The frequency and severity of RDS were assessed with use of a simple radiographic scoring system in which pulmonary parenchymal densities and the prominence of the air-bronchogram effect were used as indicators of widespread atelectasis. Radiographs were obtained in surfactant-treated and control infants within the first 90 minutes of life as part of an initial evaluation of their pulmonary status. Subsequent examinations were performed at less than 24 hours and less than 48 hours of age. Radiographic assessment of lung disease compared consistently with coordinated data on oxygen and mean airway pressure requirements of the infants. Both indicated a significantly decreased frequency and severity of RDS in the infants treated with surfactant. The results provide supporting evidence of the effectiveness of exogenous lung surfactant replacement in mitigating RDS in very premature infants. 相似文献
79.
Using sequences of the ribosomal second internal transcribed spacer (ITS2), PCR primers were designed for the differentiation
of the gastrointestinal nematode genera Ostertagia, Cooperia, Nematodirus, Haemonchus and Trichostrongylus. Single eggs or larvae from faeces could be differentiated without previous DNA extraction. Quantification of the PCR result
proved to be difficult because the DNA content between eggs from fresh or 24-h-old faeces varied considerably.
Received: 12 February 1999 / Accepted: 2 May 1999 相似文献
80.
Meniscal injuries: detection using MR imaging 总被引:15,自引:0,他引:15
Reicher MA; Hartzman S; Duckwiler GR; Bassett LW; Anderson LJ; Gold RH 《Radiology》1986,159(3):753-757
Both retrospective and blinded analyses of thin-section, high-resolution magnetic resonance (MR) images of the knee joint, produced using a solenoid surface coil, indicate that MR imaging is an effective technique for evaluating meniscal injuries. Images of 49 patients were evaluated, and the results were correlated with those of subsequent arthroscopy. A grading scale was developed to rate the index of suspicion of a meniscal tear based on the MR images. Overall, approximately 80% of menisci rated grade 4 (definite tear) or 3 (probable tear) were found to have corresponding tears at arthroscopy. In many other patients with a grade 4 or 3 meniscus in whom a corresponding tear was not found arthroscopically, meniscal tears at other sites or other abnormalities were correctly diagnosed using MR. A majority of the false-positive MR images involved the posterior horns of the menisci, the sites of most false-negative arthroscopic diagnoses. The predictive value of a negative MR image was almost 100%. Even in patients with moderate-to-large effusions, the menisci were accurately evaluated. The results imply that MR imaging is useful in the preoperative evaluation of suspected meniscal tears. 相似文献