Effects of intravenous erythromycin on antroduodenal motility in humans: non-invasive observations with real-time ultrasound

Erythromycin has been shown to act on motilin receptors on gastrointestinal smooth muscle in vitro and to accelerate gastric emptying in normal subjects as well as in patients with diabetic mellitus. To evaluate the motor pattern that accounts for this accelerated emptying, the effects of 12.5 mg/min erythromycin vs. placebo on postprandial motility of the antroduodenum was examined with real-time ultrasound in 15 normal subjects. During 10 minutes of observation, erythromycin significantly increased forward transpyloric flow episode (1.04 +/- 0.19 vs. 0.37 +/- 0.41; p < 0.05), forward transpyloric flow duration (5.79 < 4.49 vs. 3.19 < 1.72 seconds; p < 0.05) and improved antro-pyloro-duodenal coordination (0.43 +/- 0.23 vs. 0.21 +/- 0.17; p < 0.05). However, no significant differences were found for gastric peristaltic cycle (22.62 +/- 3.06 vs. 23.40 +/- 2.14 seconds; p > 0.05), retrograde transpyloric flow episode (0.13 +/- 0.16 vs. 0.18 +/- 0.29; p > 0.05), and retrograde transpyloric flow duration (1.24 +/- 0.30 vs. 1.38 +/- 0.58 seconds; p > 0.05). We conclude that erythromycin increases episode and duration of forward transpyloric flow, and improves antro-pyloro-duodenal coordination, which may play a role in accelerating gastric emptying.     

Urea release from silicate- and polymer-coated urea in water and a simulated wetland soil

Urea release rates in water (38°C) and in a simulated wetland soil system under greenhouse conditions from silicate- and polymer-coated urea (SPCU) materials have been studied. The SPCU materials were prepared by the Korea Advanced Institute of Science and Technology (KAIST), Seoul, Korea, in cooperation with the International Fertilizer Development Center (IFDC). Average urea release ( \(\overline {UR} \) ) in water was mainly a diffusion-controlled, concentration-gradient dependent process. It was markedly influenced by the extent of swelling of the coatings of granules. Under unrestricted swelling condition, \(\overline {UR} \) versus time gave an s-shaped curve with three distinct periods: namely, a delayed period, a maximum-rate period, and slow-rate period. \(\overline {UR} \) versus time curves for SPCU after placement at 0- to 2-, 5- to 10- and 10- to 15-cm depth in a simulated wetland soil system were, in general, sigmoidal but different from those in water. They were influenced by placement depths of SPCU granules in the soil, and the order of \(\overline {UR} \) at the soil depths studied was: 0–2 cm, < 5–15 cm ? 10–15 cm.     

Amylobarbitone hydroxylation kinetics in small samples of rat and human liver

1. Two micro methods for determining amylobarbitone hydroxylase activity from less than 3 mg liver are described. One is based on single-ion monitoring g.l.c.-mass spectrometry and the other on t.l.c. separation of 14C-labelled product. 2. Km and Vmax have been determined with rat liver and both needle and open biopsy samples of human liver. 3. Both methods are sufficiently sensitive and reproducible for use with 20 mg needle biopsies.     

Urinary oestrogen and plasma human placental lactogen as initial screening tests for a placental sulphatase deficiency

As a result of routine screening of ante-natal patients by urinary total oestrogens and plasma human placental lactogen (HPL) from 35 weeks, a rare placental sulphatase deficiency was indicated which was later confirmed by in vitro studies of placental enzyme activities.     

Loaded and nonloaded titanium versus hydroxyapatite-coated threaded implants in the canine mandible

A commercially pure titanium threaded implant was compared to a hydroxyapatite-coated threaded implant of similar geometric design and dimensions in the canine model. Bilateral posterior implants supported fixed prostheses, and some implants in the same mandibles served as unloaded control implants. Implants were evaluated clinically, radiographically, and histomorphometrically at the light microscope level to detect any differences in bone response to loaded conditions. No statistically significant differences were found between the two implant designs under loaded or nonloaded conditions with regard to mobility, probing depth, percentage of osseointegration, and crestal bone position.     

The Stroke Prevention Patient Outcomes Research Team. Goals and methods

BACKGROUND AND PURPOSE: The aim of the present study, based at Duke University and involving 14 other institutions, is to identify the most appropriate and cost-effective clinical strategies for prevention of ischemic (thrombotic or embolic) stroke in high-risk individuals and to design and test an intervention to disseminate this information to providers and the public. METHODS: The study uses (1) secondary data from literature review, Medicare claims, and population-based data from three epidemiological studies and (2) primary data generated in national physician and patient surveys and in demonstration trials. Phases I through III involve data collection and analysis using a decision/cost-effectiveness model and consensus development methods. Phase IV includes intervention in physicians' practice patterns. Data is collected by literature survey and abstraction, review of medical records, claims analysis, and patient and physician surveys. CONCLUSIONS: A structured decision model and a well-defined clinical focus provide a successful organization for a PORT on stroke prevention.     

Twenty-one year mortality in a dialysis unit: changing effect of withdrawal from dialysis

This study was designed in order to assess whether the Iwasaki-Hayashi (IH) catheter can be fixed to the uterine cervix easily and successfully during transcervical fallopian tube recanalization (T-FTR) with fluoroscopic guidance, to try T-FTR in special cases, and to investigate the success rate. The study included 21 infertile women with tubal obstruction, diagnosed by hysterosalpingography examined at least twice to exclude tubal spasm. Using the IH catheter, which proved to be very useful, higher therapeutic efficacy could be obtained. A patient with unilateral proximal tubal obstruction became pregnant following natural fertilization in the fallopian tube which had been recanalized by T-FTR. The success rate of recanalization, the pregnancy rate and the take-home-baby rate were 95.2%/patient, 19.0 and 19.0%, respectively.     

Design, synthesis, derivatization, and structure-activity relationships of simplified, tricyclic, 1,2,4-trioxane alcohol analogues of the antimalarial artemisinin

Novel C4-(hydroxyalkyl)trioxanes 5d and 5e were designed and synthesized based on an understanding of the molecular mechanism of action of similar 1,2,4-trioxanes structurally related to the antimalarial natural product artemisinin (1). In vitro efficacies of these two new pairs of C4-diastereomers against chloroquine-sensitive Plasmodium falciparum support conclusions about the importance to antimalarial activity of formation of a C4 radical by a 1,5-hydrogen atom abstraction. Derivatives 6, 7, and 21 of C4 beta-substituted trioxane alcohols 4a, 5d, and 5e were prepared, each in a single-step, high-yielding transformation. Four of these new analogues, 6a-c and 7, are potent in vitro antimalarials, having 140 to 50% of the efficacy of the natural trioxane artemisinin (1).     

Induction of antitumor immunity by interleukin-2 gene-transduced mouse mammary tumor cells versus transduced mammary stromal fibroblasts

BACKGROUND: Tumor cell-targeted cytokine gene transfer has been used to generate tumor cell vaccines, but this approach is limited by the need to establish and implant live tumor cells. PURPOSE: The purpose of this study was to determine if stromal fibroblasts could be used as an alternative vehicle for delivery of the cytokine interleukin-2 (IL-2) into the tumor microenvironment. We attempted to establish the feasibility of (a) genetic immunotherapy in a mammary tumor system and (b) engineering stromal fibroblasts as well as tumor cells. We compared the effects of tumor cell-mediated and stromal fibroblast-mediated local IL-2 expression on the generation of antitumor immune responses. METHODS: Retroviral vectors containing a human IL-2 gene were used to transduce a mouse mammary tumor line, 4TO7, and an immortalized but nontumorigenic fibroblast line established from syngeneic mammary fatpads. Expression of the IL-2 gene in transduced cells was determined by measuring IL-2 secretion, by RNA-polymerase chain reaction, and by immunochemistry. Groups of 5-12 BALB/c mice were injected with either 4TO7 cells or various doses of IL-2-secreting 4TO7 cells (4TO7-IL-2); tumor growth was monitored. To test whether local IL-2 expression by transduced cells could influence the growth of unmodified tumor cells, we determined tumor development in groups of mice treated with 4TO7 cells co-injected with either 4TO7-IL-2 cells or IL-2-secreting fibroblasts. RESULTS: 4TO7-IL-2 cells induced active immunity able to reject the immunizing tumor and to resist challenge with parental 4TO7 cells on the contralateral side. Mice pretreated with 4TO7-IL-2 were significantly protected compared with untreated control animals or mice pretreated with irradiated 4TO7 cells. The immunity induced by 4TO7-IL-2 cells did not protect against challenge with another subline, 4T1, which was derived from the same spontaneously arising mammary tumor as 4TO7. Co-injection of 4TO7 cells with 4TO7-IL-2 cells reduced tumorigenicity, whereas co-injection of 4TO7 cells with IL-2 secreting fibroblasts did not. CONCLUSION: Our results suggest that induction of anti-tumor immune response by local IL-2 production is most effective when the helper cytokine is secreted by the tumor cell. IMPLICATION: Our studies caution against the use of IL-2 gene-transduced syngeneic stromal cells as an alternative strategy of gene therapy for cancer. However, they may allow study of the mechanisms of tumor antigen recognition and the possible involvement of co-stimulatory signals for effective tumor vaccination by gene-modified cells.