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71.
Short-chain alkyl esters of L-dopa were administered to rats and mice via oral and rectal routes. Plasma L-dopa esters and L-dopa were determined in the systemic and portal circulation by HPLC. A comparison of isopropyl, butyl, and 4-hydroxybutyl esters of L-dopa demonstrated significantly higher levels of the esters in both systemic and portal blood samples following rectal administration than following oral administration. In most cases, oral administration resulted in nondetectable (<0.01 µg/ml) levels of the esters in plasma. Correspondingly, the plasma levels of L-dopa itself were consistently higher following rectal administration. At very high oral doses (500 mg L-dopa equivalents/kg body weight), systemic plasma levels of the butyl ester could be detected (1.25 µg/ml at 10 min), which might indicate saturation of the esterase activity of the small intestine. These studies indicate that the systemic availability of L-dopa from short-chain alkyl esters of L-dopa may be best optimized by rectal administration, which avoids the relatively high esterase activity characteristic of the small intestine.  相似文献   
72.
Bacteroides fragilis constitutes about 1% of the bacterial flora in intestines of normal humans. Enterotoxigenic strains of B. fragilis have been associated with diarrheal diseases in humans and animals. The enterotoxin produced by these isolates induces fluid changes in ligated intestinal loops and an in vitro cytotoxic response in HT-29 cells. We developed a nested PCR to detect the enterotoxin gene of B. fragilis in stool specimens. After DNA extraction, a 367-bp fragment was amplified with two outer primers. The amplicon from this reaction was subjected to a second round of amplification with a set of internal primers. With these inner primers, a 290-bp DNA fragment was obtained which was confirmed as part of the B. fragilis enterotoxin gene by Southern blotting with a nonradioactive internal probe and a chemiluminescence system. By this approach, B. fragilis enterotoxin gene sequences were detected in eight known enterotoxigenic human isolates and nine enterotoxigenic horse isolates. No amplification products were obtained from DNA extracted from 28 nonenterotoxigenic B. fragilis isolates or B. distasonis, B. thetaiotaomicron, B. uniformis, B. ovatus, Escherichia coli, or Clostridium difficile. The sensitivity of this assay allowed us to detect as little as 1 pg of enterotoxin DNA sequences or 100 to 1,000 cells of enterotoxigenic B. fragilis/g of stool. Enterotoxin production of all isolates was confirmed in vitro in HT-29 cells. A 100% correlation was obtained between enterotoxin detection by cytotoxin assay and the nested PCR assay. This rapid and sensitive assay can be used to identify enterotoxigenic B. fragilis and may be used clinically to determine the role of B. fragilis in diarrheal diseases.  相似文献   
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74.
Objectives.To test the safety, efficacy, and toxicity of gene therapy using wild-type p53-expressing adenovirus (Ad-CMV-p53) in a nude mouse model with intraperitoneal (ip) 2774 human ovarian cancer cell line that contains a p53 mutation.Study design.An initial study of adenovirus tolerance was determined in nude mice by a single ip injection of increasing doses of Ad-CMV-p53. Nude mice were implanted with an LD100dose of 1 × 107cells. To study the efficacy and specificity of Ad-CMV-p53 treatment, the mice received treatment with different adenovirus constructs. One group received Ad-CMV-p53 and another group received a control adenovirus construct, Ad-CMV-βgal. To study the treatment response to Ad-CMV-p53, the mice were divided into groups and received various treatment schedules of 1 × 108pfu of Ad-CMV-p53.Results.The mice tolerated Ad-CMV-p53 without adverse effects at doses of 1 × 108pfu. The response to Ad-CMV-p53 showed significant survival duration in each dose regimen, with a survival time greater than that of untreated animals (P= 0.0173). However, no statistically significant survival advantage was observed between Ad-CMV-p53- and Ad-CMV-βgal-treated mice.Conclusions.These studies show that at the adenovirus dose and administration regimen used, there is effective but not specific 2774 tumor growth inhibitionin vivo.Efficient introduction of biologically active genes into tumor cells would greatly facilitate cancer therapy. Thus, although promising, these results caution that much effort will be required to realize the potential for clinical application of adenovirus-based ovarian cancer gene therapy.  相似文献   
75.
Fifty patients with suspected intra-abdominal abscess were investigated prospectively with ultrasound and with 99mTc-hexamethylpropylene-amine oxime (HMPAO) isotope labelled mixed leucocytes, using 111-In tropolonate granulocyte scanning as the reference standard. Twenty five patients had inflammatory bowel disease (three were postoperative): 21 of these had Crohn's disease and four had ulcerative colitis. The remainder comprised nine with postoperative fever and 16 with fever and abdominal pain. An abscess was diagnosed when focal activity on serial 111-In tropolonate and 99m-Tc-HMPOA images at one, three, and 24 hours resulted in activity at least equal to liver activity at 24 hours. Thirteen abscesses were diagnosed using each type of white cell scanning, resulting in 100% sensitivity for 99m-Tc-HMPAO compared with 111-In tropolonate. Bowel inflammation was easily distinguished from abscess on serial images. Eight of these 13 abscesses were detected by ultrasound. Altogether 17 abscesses were found. Ultrasound detected 12, including four liver abscesses which were not purulent and had not been detected by white cell scanning. Ultrasound had a sensitivity of 71% (12 of 17) and a specificity of 87% (33 of 38) using all confirmed abscesses as the reference standard. White cell scanning showed a sensitivity of 76% (13 of 17: as a result of the four non-purulent liver abscesses) and a specificity of 100%. 99m-Tc-HMPAO scanning is as accurate as 111-In tropolonate scanning, and has several advantages including simplicity, availability, superior image quality, and reduced radiation dose. Both methods are more sensitive and specific than ultrasound for intra-abdominal abscess detection but ultrasound is advisable if a neutrophil infiltrate is not suspected.  相似文献   
76.
The development of a unifying framework for conceptualizing the commonalities in various forms of substance abuse must encompass the data base focused upon the stimulus functions of drugs. In the first instance, for example, the research on drug self-administration has provided convincing evidence of a remarkable concordance between laboratory animals and human substance abusers in the reinforcing stimulus functions of a range of chemical agents. The recognition of these cross-species and cross-drug generalities has radically changed conceptualizations of substance abuse from a reactive to a more active process and has encouraged the kind of functional analysis of drug-seeking and drug-taking that has proven productive and useful in the study of other behavioral interactions. In this regard as well, recent refinements in the analysis of the discriminative stimulus functions of drugs have provided a more comprehensive basis for characterizing a chemical agent's spectrum of action and evaluating its abuse liability. While the correlation between the discriminative stimulus functions and the reinforcing stimulus functions is remarkably high for some drug classes, there are notable exceptions. Finally, the assessment of abuse liability requires an analysis of the eliciting stimulus functions of drugs as reflected by the physiological and behavioral changes, both acute and chronic, that follow drug administration. The methods used to evaluate both physiological dependence and behavioral toxicity in relationship to sensory and motor effects for a range of abused drugs have depended heavily upon an assessment of the eliciting stimulus functions of such compounds.  相似文献   
77.
The epithelial cells of the colonic mucosa of the animal have proved impossible to culture using standard tissue culture techniques. Immortalization of adult colonic epithelial cells has been unsuccessful due to the lack of DNA synthesis in these cells once they are isolated from the tissue. Recently an unique transgenic mouse bearing a temperature sensitive mutant of the known immortalizing gene, SV40 large T has become available. The advantage of this mouse is that the SV40 large T gene is expressed in every cell. Active immortalizing protein is produced in each cell at the permissive temperature. We have used colonic mucosa from these mice to initiate cultures of epithelial cells from the colon of adult mice. The cells grow readily at the permissive temperature but die within 7 days at the non-permissive temperature. The methods used to develop these cultures are described.  相似文献   
78.
OBJECTIVE: To identify spatial patterns of changes in infant mortality rates and proportions of low-birth-weight live births observed in 1994. SETTING: Canada. SUBJECTS: Live births and infant deaths in Canada between 1987 and 1994. Data for Newfoundland were unavailable for 1987 through 1990. OUTCOME MEASURES: Annual infant mortality rates (crude and after excluding live newborns weighing less than 500 g); proportion of live births by low-birth-weight category (500-2499 g). RESULTS: Nova Scotia, New Brunswick, Quebec and Manitoba had lower crude and adjusted infant mortality rates in 1994 than in 1993. Newfoundland, Saskatchewan, Alberta and British Columbia had higher rates in 1994 than in 1993. The crude rate in Ontario was lower, and the adjusted rate higher, in 1994 than in 1993. A downward trend in the proportion of low-birth-weight live births was observed in Quebec (chi(2) for trend = 29.2, p < 0.01). Conversely, an upward trend was observed in Ontario (chi(2) for trend = 241.3, p < 0.01). However, the increase may have been due to data errors, especially in 1993 and 1994, involving truncation of ounces in 2 digits to 1 digit (e.g., 5 pounds 10 ounces became 5 pounds 1 ounce). CONCLUSIONS: Although the marginal increases in infant mortality observed in several provinces could be the result of random variation, future trends should be closely monitored. The proportion of low-birth-weight live births in Canada (excluding Ontario) appears to be stable, with Quebec showing significant reductions. The errors in data for Ontario need to be corrected before trends can be estimated for that province and for Canada as a whole.  相似文献   
79.
80.
A study was made on the causes of unsatisfactory progress in immunization coverage in an area of Tamil Nadu, southern India. The findings led to the appointment of additional community health workers (CHW), improvement in supervision, the enhancement of accessibility to services through an increase in the number of peripheral clinics and the organizing of temporary clinics, and the concentration of effort on underprivileged groups. As a result, immunization coverage was more than doubled. The Community Health and Development Project, a primary health care program serving 68 villages since 1981 with a population of about 80,000 was the site of the study which was conducted by discussions with staff and various members of the community. Issues explored were nonacceptance or dropout reasons, and specific factors affecting immunization coverage. A special effort was made to obtain the views of staff working at the periphery, particularly CHWS. The service area was divided into 4 sectors and the CHWS, auxiliary nurse midwives, community health nurses and other development staff in each were brought together for discussions. Views were also solicited from mothers' clubs and youth groups and in meetings with village leaders. Issues raised were further considered by supervisory staff. Statistical studies and other studies were done to clarify doubtful issues and test hypotheses emerging from the discussion. Poor immunization coverage was linked to inadequate supervision of CHWs, scattered communities (village with houses clustered together had better acceptance rates), difficulty of access to health services (distance factors), and low economic and educational status. In light of the study findings, community health workers were increased from 42 in 1984 to 57 in 1987 to cover all the villages, with modifications in selection method to make the worker acceptable to all sections of the villages; abolishment of the auxiliary nurse midwife and addition of a new category, health aide, to link the CHW and the community health nurse, increase of peripheral clinics from 37 to 75 and holding of more temporary clinics, more efforts to reach all socioeconomic groups and increased health education through film shows, drama, and work with village groups.  相似文献   
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