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Biomedical subjects

D L Hay

Publications and source records attributed to D L Hay.

At least 37 records · Page 2Linked to original sources

A comparative scanning electron microscopic study on degradation of absorbable ligating clips in vivo and in vitro.

Using scanning electron microscopy, the degradation characteristics of two absorbable ligating clips, Absolok (polydioxanone) and Lactomer (poly-L-lactide-co-30%-glycolide) have been studied under in vivo and in vitro conditions. The rate of Absolok clip degradation was significantly greater than that of Lactomer clip degradation both in vitro and in vivo. The rate of degradation of Lactomer clips significantly increased and they showed a greater change in proportion of breakdown in vivo than in vitro compared to Absolok clips. The Absolok clip breakdown began with the formation of surface undulations which later developed into fissures. The undulations appeared on the clip surface as early as 7 days and by 2 weeks developed into fissures. The initial appearance of the fissures was at the edge of the clips particularly at the mating surface. The thickness of layers forming the fissures gradually decreased and by 15 weeks the layers appeared as very thin sheets of materials. The high energy areas (locking and molding points) were more resistant to breakdown and the remains of the clips were still present 25 weeks after initiation of the experiments. The Lactomer clips showed very little sign of degradation in vitro even after 10 weeks of incubation. However, in the in vivo experiments undulations formed on the clip surface as early as 2 weeks postimplantation. These clips also showed fissures similar to those observed on Absolok clips.

Animals↗

Locking mechanism strength of absorbable ligating devices.

The locking mechanism strengths of the absorbable Absolok and Lactomer ligating clips and the absorbable Lactomer staple have been determined following implantation in an animal model. Three sizes of each type of clip and the single size of staple were enclosed in open mesh nylon pouches and implanted subcutaneously in rabbits for periods of 4, 7, 14, 21, and 28 days before tensile testing of the lock mechanisms. No change in the lock mechanism strength was detected for the Absolok clips before 21 days. The Lactomer clips and staples, however, showed significant decrease in lock mechanism strength within 7 days of implantation, this loss increasing with longer implantation times. A proportion of all the devices were found to have dissolved to an extent that precluded testing at 21 and 28 days. The findings indicate that the lock mechanisms of absorbable ligating clips differ significantly in their short-term (30 days) durability.

Animals↗

Midcycle changes of 17-OH-progesterone levels in women superovulated with clomiphene citrate and human menopausal gonadotropin for in vitro fertilization.

The dynamics of 17-alpha-hydroxy-progesterone (17-OHP) production during the onset of the luteinizing hormone (LH) surge were evaluated at 8-hour intervals and correlated with plasma estradiol (E2), LH, and progesterone (P) in 22 women superovulated for in vitro fertilization. Plasma 17-OHP levels rose 8 to 16 hours before the earliest rise in LH and P in 18% of patients, but had risen significantly in 82% of patients by the onset of the LH surge. In the late follicular phase, 17-OHP levels correlated significantly with E2 and LH levels, and the number of follicles greater than 10 mm. Because rising 17-OHP levels preceded the LH surge in only a few patients, it has no clinical value as a marker for human chorionic gonadotropin administration for timed oocyte recovery. Plasma 17-OHP levels, however, may complement LH levels better than P levels in determining the most appropriate stage for surge-timed oocyte retrieval.

17-alpha-Hydroxyprogesterone↗

Placental histology and the production of human choriogonadotrophin and its subunits in pregnancy.

The relation between placental histology and the levels of human chorionic gonadotrophin (hCG) and its alpha-hCG and beta-hCG subunits was studied using monoclonal antibodies in immunohistochemical and immunoassay procedures. Between 4 and 9 weeks gestation an increasing ratio of cytotrophoblasts to syncytiotrophoblasts in placental villi corresponded to rising hCG levels, with beta hCG levels declining from 4% to less than 1% of hCG levels. After 8-10 weeks gestation, declining numbers of cytotrophoblasts in villi and the formation of the definitive placenta coincided with falling hCG, rising alpha hCG and insignificant beta hCG levels. Between 18 and 35 weeks, a secondary twofold rise in hCG levels coincided with a similar increase in average placental mass. It is proposed that hCG synthesis in syncytiotrophoblasts depends on the rate of differentiation of cytotrophoblasts into syncytiotrophoblasts.

Cell Differentiation↗

Histological origins of discordant chorionic gonadotropin secretion in malignancy.

Serum hCG, alpha hCG, and beta hCG levels were measured using monoclonal antibodies in women with trophoblastic disease (n = 138) and germ cell neoplasia (n = 123). Elevated serum beta hCG levels were present initially in the majority of the trophoblastic disease patients. By 12 weeks postevacuation raised serum beta hCG levels were detected in 42% of patients with malignant disease compared to 12% of patients with benign disease. No significant relationship was found between the initial alpha hCG levels and malignancy or resistance to chemotherapy. Increased serum free subunit levels did not distinguish between choriocarcinoma or benign hydatidiform moles, but increasing beta hCG to hCG ratios identified patients with high risk disease requiring multiagent chemotherapy. In nongestational malignancy, increased subunit levels occurred in fewer patients and to a lesser extent. Higher beta hCG and alpha hCG levels coincided with a histology of proliferating intermediate and cytotrophoblast cells, respectively, while high hCG levels occurred in association with syncytial proliferation. A histological mechanism for hCG synthesis is proposed, whereby mRNA for hCG subunits in syncytium depends on supplies of presynthesized mRNA introduced by fusion from differentiating cytotrophoblasts. Abnormalities in the extent and rate of differentiation would result in imbalanced subunit secretion.

Choriocarcinoma↗

Chorionic gonadotropin secretion by human embryos in vitro.

Embryos (n = 38) from an in vitro fertilization (IVF) program, unsuitable for transfer or cryopreservation, were maintained in culture for 14 days. The time course of hCG secretion into culture fluid was compared to observed embryo development. The earliest significant hCG rise was detected at day 7 post insemination for a partially hatched blastocyst, with hCG levels increasing 50-fold following blastocyst attachment to the surface of the culture vessel. Secretion of hCG was amplified by the addition of serum. There was no significant free alpha hCG or beta hCG secretion between days 6-12. We conclude that hCG production depends on the pathway of cytotrophoblast differentiation and commences with the appearance of the G1 phase in embryonic cells at the late blastocyst stage.

Chorionic Gonadotropin↗

Effects of bacterial infection on absorbable vascular ligating clips.

Electron microscopic observations of two implanted absorbable clips, Absolok and Lactomer, infected with Escherichia coli and Streptococcus faecalis, were carried out. An overgrowth of bacteria was observed over the entire surface of the clips. The mating surfaces of the Lactomer clips and the locking mechanisms of both types of clip were more heavily infected--that is, provided better support for bacterial growth--than other areas of the clips in the initial postimplantation period. However, with longer periods (up to seven days), the initial bacterial deposits developed into a thick, plaquelike layer. This layer appeared to restrict access to the surfaces such that the infected clips degraded at a much slower rate than did the noninfected clips, particularly Lactomer clips, on which little morphologic change was detectable seven days after implantation.

Animals↗

Tissue reactions to absorbable ligating clips.

Scanning electron microscopy was used in a comparative ultrastructural study of biodegradable ligating clips, the Absolok (polydioxanone) and the Lactomer (copolymer of glycolic and lactic acids), implanted subcutaneously in rabbits. The inflammatory response and tissue reactions to the implanted clips and their effects on clip breakdown were studied. By the first week after implantation, numerous inflammatory cells adhered to the clip surfaces, with occasional fibroblasts present. By two weeks after implantation there was a reduction in the number of inflammatory cells, but the number of fibroblasts gradually increased, resulting in encapsulation of the clips. The thickness of the fibrous tissue capsule, formed by a variety of collagen fibers, gradually increased 5-25 weeks after implantation. Residues from the Lactomer clips were still present within the encapsulating tissue at 25 weeks. In contrast, clips enclosed in nylon pouches were totally degraded, and no residues were detectable at 25 weeks. Tissue reactions similar to those observed for nonpouched implanted clips were seen over the entire external surface of the pouches.

Animals↗

The use of nylon pouches to prevent cellular attachment to implanted materials.

A nylon pouch system has been developed to permit the in vivo exposure of implantable materials to tissue fluids without complications arising from cellular attachment or from the bacterial attack. SEM observations have indicated that the pouches were effective in reducing the ingress of bacteria as well as reducing, and in some cases eliminating, cell infiltration through their mesh structure. Over a 7 d implantation period, the exterior surfaces of the nylon pouches were heavily infested with microorganisms but there was minimal growth of bacteria within the pouches. Non-infected pouches that were implanted for up to 25 wk showed heavy deposits of cellular matter on the external surfaces of the pouches and minimal deposits within the pouches.

Absorption↗

Evaluating human choriogonadotropin heterogeneity in nongestational malignancy with monoclonal immunoassays.

The ectopic production of human choriogonadotropin (hCG) and its free alpha- and beta-subunits was evaluated in 195 patients with nongestational malignancy. Dimer hCG was the predominant species secreted. Significant levels of free beta-hCG were detected in 11% of patients, and represented 1.6-12% of immunoreactive hCG. In these patients the ratio of free beta-subunit to hCG remained constant during their follow-up period. Significant levels of free alpha-hCG occurred in 1.5% of patients, but were secreted independently of free beta-hCG. These findings indicate that immunoassays specific for dimer hCG would not be significantly disadvantaged in monitoring malignancy, and that free beta-hCG subunit levels have limited application as a tumor marker.

Antibodies, Monoclonal↗

Ectopic pregnancy--potentials for diagnosis using ultrasound and urine and serum pregnancy tests.

The ultrasound findings from 260 patients with a clinical suspicion of ectopic pregnancy have been analysed and correlated with the results of urine pregnancy tests and tests of serum LH and/or HCG levels. Most importantly in a practical clinical context, it was found that a negative serum test virtually excludes an ectopic pregnancy, and an empty uterus with an adnexal mass and/or the presence of free fluid together with a positive urine test gives a very high probability of an ectopic pregnancy. The absolute diagnosis of an ectopic pregnancy by the demonstration of a living fetus outside the uterus is an uncommon finding (8%). Conversely, an empty uterus alone on ultrasound examination in the absence of other ultrasound findings in those patients with a positive serum test is not a reliable guide to the presence of an ectopic pregnancy unless there is an irrefutable conception date at least 5 weeks previously. It is recommended that pathology laboratories and ultrasound departments establish absolute levels of HCG above which an intrauterine pregnancy should always be visible within the uterus. Given appropriate attention to the clinical condition of the patient, the combined use of diagnostic ultrasound, simple urine pregnancy tests and serum assays of beta HCG levels goes a long way to discriminating between those patients with and those without an ectopic pregnancy.

Chorionic Gonadotropin↗

Automation and limitation of 17 beta oestradiol dehydrogenase in monitoring ovarian function.

An automated enzymatic assay which measures combined concentrations of urinary oestrone and oestradiol within 15 minutes of hydrolysis has been developed using placental 17 beta oestradiol dehydrogenase. This assay is comparable to radioimmunoassay in its precision and sensitivity and is quicker, more convenient, and more economical. The 17 beta oestradiol dehydrogenase assay was used to monitor ovarian response in infertile women being treated through stimulated ovarian cycles or in vitro fertilisation programmes. Because the assay did not respond to oestriol it was less reliable than total urinary oestrogens in monitoring ovarian responses, particularly during treatment with drugs which enhanced oestriol excretion. In natural ovulatory cycles rising 17 beta oestradiol dehydrogenase values preceded peak luteotropin concentrations by up to 18 hours and improved detection of ovulation. The 17 beta oestradiol dehydrogenase assay processes large numbers of urine samples quickly and economically and enables accurate monitoring of oocyte maturity and ovulation.

17-Hydroxysteroid Dehydrogenases↗

Discordant and variable production of human chorionic gonadotropin and its free alpha- and beta-subunits in early pregnancy.

Monoclonal antibodies specific to dimer hCG (alpha beta), free beta-subunit (beta hCG), free alpha-subunit (alpha hCG), and total beta hCG (dimer + free beta hCG) were used to monitor discordant production of hCG and its subunits during the early stages of embryo implantation. Sera collected 3 to 22 days postovum retrieval were assayed from patients participating in an in vitro fertilization program. In the majority of patients with ongoing pregnancies (n = 16), rising levels using the dimer hCG assay were first detected at an average time of 9.2 days post retrieval compared to 8.3 days for the total beta hCG assay and 6.5 days for the free beta hCG assays. Between days 5 to 9 after retrieval, the rises in the total beta hCG assay were due to predominantly free beta hCG subunit production. The proportion of total beta hCG levels due to free beta hCG subunits declined progressively from day 9 to less than 5% by day 22. Free alpha hCG levels remained low with rising levels first detected from day 18. A second group of patients (n = 12) had delayed, slowly rising levels in the total beta hCG assay which were first detected at an average of 12.4 days and associated with mainly biochemical pregnancies (n = 10). In these patients, rising total beta hCG levels were due to predominantly free beta hCG production. The subsequent loss of their pregnancy may be due to poor luteal support associated with delayed rises in dimer hCG levels. In nonconceptual cycles (n = 47) no significant rises were detected in dimer or free hCG subunits. Although the major form of hCG in circulation is dimer hCG, the origin of free beta hCG production in the early stages of implantation may be due to poorly differentiated trophoblastic tissue. Thus falling levels of free beta hCG subunits associated with increasing dimer hCG production may reflect increasing alpha hCG production by the proliferating layer of cytotrophoblastic cells.

Adult↗

Monitoring early production of chorionic gonadotrophin (HCG) following in vitro fertilization and embryo transfer.

A rapid, sensitive assay was developed for monitoring HCG production and applied to serum and urine collection between days 4 and 20 after OPU in 55 patients treated by ovarian hyperstimulation and IVF. Eleven ongoing pregnancies, 2 ectopic pregnancies and 1 clinical abortion resulted. The earliest detection of a rise in HCG was on day 7 after OPU. The HCG values showed that trophoblastic tissue functioned transiently in another 11 patients and probably in another 5. Thus evidence for functioning trophoblastic tissue was obtained in a total of 30 patients (55%). These findings are important for the further improvement of IVF. No antibodies to administered HCG were detected.

Antibodies↗

Oncofetal antigens in ovarian cyst fluids.

The levels of five oncofetal antigens were measured in ovarian cyst fluids. Significantly raised levels of carcinoembryonic antigen (CEA), human chorionic gonadotropin, beta 2-microglobulin, and alpha-fetoprotein were found in ovarian cyst samples. Human placental lactogen was not detectable in any samples. Mucinous cyst fluids demonstrated higher levels of CEA than serous fluids in both malignant and benign conditions. We could not distinguish between malignant and benign conditions with any of the markers. Except for CEA, there is no difference in values between mucinous and serous cystadenocarcinomas.

Antigens, Neoplasm↗

Rapid acetylcholinesterase screening test for neural tube defect.

A 5-min optimized automated assay for measuring acetylcholinesterase (AChE) and total cholinesterase (ChE) in amniotic fluids is described in which a centrifugal analyzer is used. Total ChE was measured by using acetylthiocholine iodide and monitoring the color developed after 5,5'-dithiobis(2-nitrobenzoic acid) is added. We evaluated four direct and indirect procedures for measuring AChE in which thiocholine is generated. These methods involve either the specific enzyme inhibitors ethopropazine and BW284C51 or the specific substrates S-butyrylthiocholine and acetyl-beta-methylthiocholine. We found the last method distinguishes normal pregnancies most efficiently from those with neural tube defect. Filtering samples through 0.22-micron membrane filters before analysis decreased the incidence of false positives. Significantly increased AChE concentrations were noted in all abnormal pregnancies (n = 45) and in 4.8% of normal pregnancies (n = 310). The rapid AChE assay involving acetyl-beta-methylthiocholine, when applied alongside a rapid alpha-fetoprotein assay, increases the efficiency of screening programs for pregnancies with neural tube defect to 99.4%. It also identifies samples with negative results for alpha-fetoprotein that require further examination by the sensitive gel-electrophoretic test for AChE.

Acetylcholinesterase↗

Evaluating fetomaternal hemorrhage by alphafetoprotein and Kleihauer following therapeutic abortions.

In a survey of 75 patients at 6-11 weeks gestation, fetomaternal hemorrhage (FMH) was detected by significant rises (greater than 2 S.D.) in maternal alphafetoprotein (AFP) levels in 57% of patients, while increased fetal cells were detected by the Kleihauer test in 24% of patients. With increasing gestation, FMH was detected more readily by both tests; however, in evaluating FMH at less than 10 weeks gestation. AFP was found to be a more sensitive and reliable marker than the Kleihauer test. We suggest that there is a gray zone for the Kleihauer test in early gestation, when erythroblasts containing embryonic hemoglobins are gradually replaced in the fetal circulation by erythrocytes containing fetal hemoglobin.

Abortion, Therapeutic↗

Acupuncture therapy for the treatment of tobacco smoking addiction.

Acupuncture has been reported as an effective treatment for some addictions. The purpose of this study was to evaluate acupuncture treatment effect on the cigarette smoking habit with a motivated population in a controlled clinical setting. From a volunteer research population, sixteen matched pairs were assembled according to age, sex, and severity of smoking habit. Research subjects were randomly assigned to real or sham acupuncture treatment groups. Self-reported cigarette logs were measured pre-treatment and post-treatment. Analysis of variants confirmed homogeneity of group pre-treatment cigarette consumption. Cigarette consumption significantly decreased in both th e real and sham treatment groups. Treatment group, age, sex, or severity of smoking habit were not significant factors in treatment effects for cessation of smoking. Legitimate crossover treatment for sham research group showed a significant decrease (p less than or equal to 0.05) in cigarette consumption; this change was not statistically different from change in cigarette consumption during placebo treatment. A discussion of acupuncture point selection rationale is made as is an analysis of Tehchi sensations and subjective reports of appetite for cigarettes. Acupuncture did not enhance the cessation of cigarette smoking in this study.

Acupuncture Therapy↗