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Biomedical subjects

J Chu

Publications and source records attributed to J Chu.

At least 19 recordsLinked to original sources

Coordinated regulation of vascular endothelial cell growth and prostacyclin production by epidermal growth factor: evidence of clonal variations among rat aortic endothelial cells.

Rat aortic endothelial cells were found to exhibit clonal variations in response to EGF stimulation in cell growth and prostacyclin synthesis. EGF-induced growth and prostacyclin synthesis appeared to be regulated in a coordinated manner in that a clone with a higher response to EGF growth stimulation also exhibited a higher response to EGF-stimulated prostacyclin synthesis. This observation implies a possible involvement of prostacyclin synthesis in some of the biological effects of EGF on vascular endothelial cells.

Animals

Physiological basis for an animal model of the renal Fanconi syndrome: use of succinylacetone in the rat.

1. The biochemical basis for the human renal Fanconi syndrome, including glucosuria, phosphaturia and aminoaciduria, remains enigmatic. This is due, in part, to the lack of an appropriate animal model. Since there is an association between the human genetic disease hereditary tyrosinaemia, for which urinary excretion of the compound succinylacetone constitutes a biochemical marker, and a renal Fanconi syndrome, we have examined the relationship between succinylacetone and renal tubular function in the rat. 2. Intraperitoneal injection of succinylacetone for 3 consecutive days into adult male Sprague-Dawley rats resulted in succinylacetone plasma concentration of 3 mmol/l. This concentration was associated with glucosuria, aminoaciduria, polyuria, reduced renal phosphate reabsorption and normal creatinine clearance. In addition, urinary porphobilinogen and total porphyrin excretions were markedly reduced. In animals permitted to recover for 7 days after succinylacetone administration, these renal functional changes remitted partially or completely. Ultrastructural examination of the kidneys after the 3 days of treatment showed no fine structural changes. 3. We conclude that the physiological alterations produced in normal rat renal tubules by succinylacetone provide the basis for the study of the biochemical changes underlying the human renal Fanconi syndrome.

Amino Acids

Haematological effects of inhalation of N-formyl-methionyl-leucyl-phenylalanine in man.

BACKGROUND: N-Formyl-methionyl-leucyl-phenylalanine (FMLP) is a bacterial oligopeptide which stimulates neutrophil chemotaxis, degranulation and superoxide generation. Inhalation of FMLP produces bronchoconstriction in man; in the rabbit this is in part neutrophil dependent. The effects of inhalation of FMLP on peripheral blood leucocytes in normal subjects has been studied. METHODS: This was an open study in non-asthmatic subjects. Change in total peripheral white cell count were studied for 15 minutes after inhalation of 0.4 mumol FMLP in six subjects. Change in total and differential white cell count and spontaneous neutrophil chemiluminescence were then studied five and 30 minutes after inhalation of 0.4 mumol FMLP (n = 7) or diluent (n = 4). Finally, leucocytes from three subjects were labelled ex vivo with technetium-99m labelled sulphur colloid and reinfused. The effect of inhalation of FMLP or diluent on pulmonary neutrophil flux was studied by continuous gamma scanning of a pulmonary window. RESULTS: Leucopenia occurs rapidly after inhalation of FMLP, the nadir of the white cell count (53% of baseline) occurring at four minutes. This was followed by a rebound increase in white cell count evident at 15 minutes (154% of baseline). Five minutes after inhalation of 0.4 mumol FMLP, neutropenia (17% of baseline) and monocytopenia (40% of baseline) were seen followed again by a neutrophilia (213% of baseline at 30 minutes). The eosinophil count was significantly reduced at 30 minutes (24% of baseline). Neutrophil chemiluminescence was elevated (186% of baseline) at the time of the neutropenia. There was no influx of labelled cells to the lung during the period of neutropenia. CONCLUSION: FMLP inhalation activates circulating leucocytes. In vivo production of FMLP in the airway could contribute to bronchial inflammation during bacterial infection.

Administration, Inhalation

[Specific killing of human leukemic T-cells by a monoclonal antibody coupled to the cytotoxin from Chinese cobra].

The immunotoxin (IT) was prepared by conjugating cytotoxin from Chinese Cobra (Naja naja Atra) venom with monoclonal antibody (McAb) Wu71 directed to human T-cells. First, calcium ions were used to suppress the cytolytic reaction while cell antigen was allowed to react with McAb. Then magnesium ions and the chelating agent EGTA were used to abolish the calcium inhibition. With this treatment, the IT showed high cytotoxicity for the leukemic cell line CEM, which was antigen positive (82.4% of the cells were killed at a concentration of 0.5 x 10(-6) mol/L of IT), but very little cytotoxicity for the antigen negative cell line Raji (23.3% cells were killed at the same concentration). Under scanning electron microscopy, it could be seen that the cell membranes of CEM were broken by IT, and the cells had died. The results suggest that the McAb Wu71 plus cytotoxin IT has potential application in leukemia therapy.

Antibodies, Monoclonal

Progestagen supplementation of exogenous oestrogens and risk of endometrial cancer.

The favourable effects of exogenous progestagen on the endometrium are well known, but have not been adequately quantified with respect to endometrial cancer. The benefits of progestagen need to be weighted against its possible untoward effects on the risk of breast cancer and cardiovascular disease. A population-based case-control study of endometrial cancer was undertaken to evaluate the benefits of progestagen use. 158 incident cases were identified between 1985 and 1987 among women aged 40-64 years who were residents of King County, Washington. Detailed interviews were conducted and the responses were compared with those of 182 controls selected by random telephone digit dialling. The risk of endometrial cancer among women who had used unopposed oestrogen for more than 3 years was over five times that of women who had used no hormones (relative risk [RR] 5.7, 95% confidence interval [Cl] 2.5-12.8), whereas those who had also used a progestagen for at least six months of that time had an RR of only 1.6 (95% Cl 0.6-3.9). The RR differed according to days per month that progestagen was used: 2.4 (0.6-9.3) for progestagen use of less than 10 days per month versus 1.1 (0.4-3.6) for use of 10 or more days per month. These results provide additional evidence that the use of progestagen for 10 or more days per cycle can reduce the excess risk of endometrial cancer associated with long-term postmenopausal oestrogen use.

Adult

Tubal sterilization and subsequent ectopic pregnancy. A case-control study.

OBJECTIVE: To assess the relative risk of ectopic pregnancy associated with postpartum or interval tubal sterilization. DESIGN: Case-control study using a comparison group of women of reproductive age at risk of pregnancy. SETTING: Group Health Cooperative of Puget Sound, a health maintenance organization based in Seattle, Wash. organization based in Seattle, Wash. PARTICIPANTS: Cases were 249 enrollees diagnosed as having an ectopic pregnancy between October 1, 1981, and September 30, 1986. Controls were 835 randomly selected enrollees matched to cases on age and county of residence. MEASUREMENTS: Information on interval sterilization history was obtained from interviews, examination of medical records, automated hospitalization files and a previously validated algorithm. A logistic regression model was used to estimate relative risks (RRs) for sterilized women compared with women using other types of or no contraception at the reference date. RESULTS: Controlling for age, county, race, smoking, income, gravidity, and prior use of a Dalkon Shield intrauterine device, the risk of ectopic pregnancy in women who had undergone interval sterilization was 3.7 (95% confidence interval [CI], 1.7 to 8.0) times that of women currently using oral contraception and 2.8 (95% CI, 1.5 to 5.5) times that of women currently using barrier contraceptive methods. Use of interval sterilization was associated with a risk of ectopic pregnancy similar to that of women using intrauterine devices (RR, 0.8; 95% CI, 0.4 to 1.7) and a risk lower than that of women who were not using contraception (RR, 0.2; 95% CI, 0.1 to 0.3). The corresponding RRs associated with postpartum sterilization were lower: 1.2 (95% CI, 0.3 to 3.9), 0.9 (95% CI, 0.3 to 2.8), 0.3 (95% CI, 0.1 to 0.8), and 0.1 (95% CI, 0.0 to 0.2), respectively. CONCLUSION: Tubal sterilization provides some protection against extrauterine as well as intrauterine pregnancy. It is likely that postpartum sterilization can be a safe alternative to all types of temporary contraception in terms of risk of ectopic pregnancy, while some types of interval sterilization may lead to an increased risk, in comparison with use of oral contraceptives or barrier methods.

Adolescent

Dose-volume histograms.

A plot of a cumulative dose-volume frequency distribution, commonly known as a dose-volume histogram (DVH), graphically summarizes the simulated radiation distribution within a volume of interest of a patient which would result from a proposed radiation treatment plan. DVHs show promise as tools for comparing rival treatment plans for a specific patient by clearly presenting the uniformity of dose in the target volume and any hot spots in adjacent normal organs or tissues. However, because of the loss of positional information in the volume(s) under consideration, it should not be the sole criterion for plan evaluation. DVHs can also be used as input data to estimate tumor control probability (TCP) and normal tissue complication probability (NTCP). The sensitivity of TCP and NTCP calculations to small changes in the DVH shape points to the need for an accurate method for computing DVHs. We present a discussion of the methodology for generating and plotting the DVHs, some caveats, limitations on their use and the general experience of four hospitals using DVHs.

Humans

Three-dimensional treatment planning for para-aortic node irradiation in patients with cervical cancer.

Three-dimensional treatment planning has been used by four cooperating centers to prepare and analyze multiple treatment plans on two cervix cancer patients. One patient had biopsy-proven and CT-demonstrable metastasis to the para-aortic nodes, while the other was at high risk for metastatic involvement of para-aortic nodes. Volume dose distributions were analyzed, and an attempt was made to define the role of 3-D treatment planning to the para-aortic region, where moderate to high doses (50-66 Gy) are required to sterilize microscopic and gross metastasis. Plans were prepared using the 3-D capabilities for tailoring fields to the target volumes, but using standard field arrangements (3-D standard), and with full utilization of the 3-D capabilities (3-D unconstrained). In some but not all 3-D unconstrained plans, higher doses were delivered to the large nodal volume and to the volume containing gross nodal disease than in plans analyzed but not prepared with full 3-D capability (3-D standard). The small bowel was the major dose limiting organ. Its tolerance would have been exceeded in all plans which prescribed 66 Gy to the gross nodal mass, although some reduction in small bowel near-maximum dose was achieved in the 3-D unconstrained plans. All plans were able to limit doses to other normal organs to tolerance levels or less, with significant reductions seen in doses to spinal cord, kidneys, and large bowel in the 3-D unconstrained plans, as compared to the 3-D standard plans. A high probability of small bowel injury was detected in one of four 3-D standard plans prescribed to receive 50 Gy to the large para-aortic nodal volume; the small bowel dose was reduced to an acceptable level in the corresponding 3-D unconstrained plan. An optimum beam energy for treating this site was not identified, with plans using 4, 6, 10, 15, 18, and 25 MV photons all being equally acceptable. Attempts to deliver moderate or high doses (50-66 Gy) to this region should be made only after careful analysis of the plan with techniques similar to those employed in this study.

Aged

Three-dimensional treatment planning considerations for prostate cancer.

Over 300 treatment plans for a total of eight disease sites based on 3-D treatment planning considerations utilizing serial CT delineated target volumes were generated by four institutions as part of an NCI supported contract to both assess the current state-of-the-art capabilities and point directions for future efforts. Two patients with stage C prostate cancer were evaluated with protocol plans which required treatment of the prostate to 70 Gy and the pelvic lymph nodes to 46 Gy. When full 3-D target definition and multiple beam arrangements were employed, all institutions were able to submit plans which scored higher on tumor coverage and had lower normal tissue complication scores compared to traditional plans. The 3-D plans using standard beam arrangements, however, were often rated as highly as the 3-D unconstrained plans due to the multiple beam arrangements already selected to optimize standard plans at most institutions. For this site, heterogeneity corrections, beam energy changes and changes in CT number did not substantially change plan scores.

Aged

Maternal cigarette smoking and the risk of tubal pregnancy.

The association between maternal smoking and the occurrence of tubal pregnancy was evaluated in a population-based case-control study of members of the Group Health Cooperative of Puget Sound, Seattle, Washington. Women hospitalized with tubal pregnancy from October 1981 through September 1986 (n = 274) were compared with reproductive-age women who were at risk of becoming pregnant during the same time period (n = 727). The relative risk of tubal pregnancy associated with ever having smoked cigarettes was 1.3 (95% confidence interval (CI) 1.0-1.8). Compared with women who had never smoked, those who smoked at the time of conception had a 40% increase in the risk of tubal pregnancy (95% CI 1.0-2.0). These results support earlier epidemiologic and nonepidemiologic reports of a greater risk of tubal pregnancy associated with current or recent maternal cigarette smoking.

Case-Control Studies

Study of BOD microbial sensors for waste water treatment control.

A microbial sensor consisting of immobilized yeast or bacterial cells and an oxygen electrode was developed for the estimation of biochemical oxygen demand (BOD). A flow-through system was used, and the response time was within 20 min. A linear relationship was observed between the relative current decrease and the BOD of the sample solution within the range of 1-45 mg/L. The storage lifetime was greater than 1 yr. The reproducibility was quite good, within 6% fsd at a concentration of 20 mg/L BOD. Satisfactory results were attained when the biosensor was applied to the determination of BOD in brewery-plant and glutamate-plant wastewater and in a river.

Biosensing Techniques

Vaginal douching and the risk of tubal pregnancy.

To explore the possible association between vaginal douching and tubal pregnancy, we interviewed 273 women who were diagnosed with tubal pregnancy at Group Health Cooperative between September 31, 1981 and October 1, 1986. Their responses were compared with responses of a random sample of 722 female members of Group Health Cooperative who were assumed to be at risk of becoming pregnant at the time the cases conceived. After adjusting for differences between cases and controls with regard to other measured risk factors, we found a modest increase in risk associated with having douched more than two times per year in the past (RR = 1.3, 95% CI: 0.9-1.8). Among women who had more than one sexual partner during their lifetime, however, the risk for those who had douched more than twice per year was somewhat higher (RR = 1.6, 95% CI: 1.1-2.3). There was an indication that women who had been exposed to Chlamydia trachomatis, as indicated by elevated antibody titers, may further increase their risk for tubal pregnancy by douching (RR = 2.4, 95% CI: 0.8-7.3). The associations found in other studies between douching and pelvic inflammatory disease, and between pelvic inflammatory disease and subsequent tubal pregnancy, argue that a relation between douching and tubal pregnancy might be anticipated. Our results offer further support for this hypothesis.

Adolescent

Genital warts, other sexually transmitted diseases, and vulvar cancer.

To determine whether specific sexually transmitted diseases were associated with an increased risk of vulvar cancer, we conducted a case-control study among residents of three countries in western Washington. We identified, interviewed, and obtained blood samples from women with in situ (n = 180) and invasive (n = 53) vulvar cancer, 18-79 years of age, who were first diagnosed with these diseases during 1980-1988. We compared their responses with those of 466 women from the general population who were identified by means of random digit dialing. On average, women with vulvar cancer reported a greater number of prior sexual partners than did controls. The risk of vulvar cancer was elevated among women who reported a prior history of condyloma (for in situ cancer, RR = 15.8; for invasive disease, RR = 17.3) or gonorrhea (for in situ cancer, RR = 2.2; for invasive disease, RR = 5.0). Women who were seropositive to herpes simplex virus type 2 (HSV-2) were at higher risk for carcinoma in situ than were controls (RR = 2.0). A history of nonspecific vaginitis, trichomoniasis, syphilis, or seropositivity to cytomegalovirus was not related to case-control status. These results indicate that only a subset of sexually transmitted diseases, particularly human papillomavirus, may play a role in the development of vulvar cancers.

Adolescent

Improving follow-up after an abnormal Pap smear: a randomized controlled trial.

Less than 60% of women diagnosed with cervical abnormalities on Pap smears return for proper surveillance and timely treatment. Previous tactics used to motivate these women to return have mainly relied on costly intensive recall efforts. Using a framework based on psychological value expectancy theory, a pamphlet was designed to motivate women with abnormal Pap smears to return for a repeat Pap smear. The effect of this pamphlet was tested in a randomized controlled trial. A total of 161 women with abnormal Pap smears were randomized and received either the pamphlet plus a notification letter or the letter only. The compliance rate was 64.2% in the intervention group and 51.3% in the comparison group (P = 0.10; two-tailed). In addition, subgroups of women who do not practice health-related behaviors were identified as groups where more intensive interventions may be needed. These results have implications for future strategies used to recall women with abnormal Pap smears.

Adult

Compliance behavior in women with abnormal Pap smears. Developing and testing a decision model.

This study investigated the reasons why women choose whether or not to seek treatment after being notified about an abnormal Pap smear in a women's clinic in Seattle. A hierarchic weighted utility model was developed from in-depth open-ended interviews with women who had an abnormal Pap smear and was used to identify beliefs and values related to the decision to seek treatment, i.e., a repeat Pap smear, for an abnormal Pap smear. Interviews with 18 women who had an abnormal Pap smear produced 12 issues pertinent to the behavior in question. These issues were grouped to form the hierarchy, and the decision model was then administered to 44 additional women. The model accurately classified the compliance behavior of 68% of study subjects. Moreover, the model differentiated persons who sought treatment for an abnormal Pap smear along several important dimensions: 1) doctor's opinion; 2) the accuracy or seriousness of the Pap smear result; 3) the importance of early detection; 4) familiarity with the treatment procedure; 5) time hassles (i.e., difficulties) involved in getting further treatment; 6) femininity concerns; 7) fear of cancer; and 8) perceived risk of cancer. These dimensions suggest specific content areas that may be used to develop low-cost compliance intervention strategies for use in clinical settings.

Adult

Use of transrectal ultrasound to evaluate direct tumour spread and lymph node status in patients with rectal cancer.

The accuracy of ultrasound in predicting the extent of local tumour spread through the rectal wall and in identifying involved perirectal lymph nodes was evaluated prospectively in 25 patients with rectal cancer. For each patient, the ultrasonic appearances recorded on videotape were compared with operative findings and/or the histology of the tumour. The extent of direct spread was classified into four curable and two incurable categories and was correctly predicted in 20 of 25 patients (80% accuracy). Lymph node status was correctly predicted in 16 of 20 patients (80% accuracy). These results suggest that pre-operative assessment of patients with rectal cancer using transrectal ultrasound is a useful technique which may assist the surgeon in his choice of operation and in the selection of those patients who may benefit from pre-operative radiotherapy.

False Negative Reactions

The relation of obstetrical volume and nursery level to perinatal mortality.

We investigated the relation of hospital delivery volume and nursery technology level to perinatal outcome in 226,164 White singleton births in Washington State, 1980-83. Level III facilities (neonatal intensive care unit) were defined by the state licensing commission. We defined the Level II (intermediate) and Level I (normal newborn) facilities using published criteria. Infants under 2000 gm born in Level III facilities had half the risk of perinatal death compared to those born in a Level I or II facility. No significant improvement was noted among level or volume groupings for normal birthweight infants. A loglinear regression model of hospital perinatal death rates showed that when birthweight and maternal risk were controlled, obstetrical volume added minimal explanatory power to level of nursery care.

Birth Weight