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Biomedical subjects

T A Doran

Publications and source records attributed to T A Doran.

At least 19 recordsLinked to original sources

Double-blind comparison of carbetocin versus oxytocin in prevention of uterine atony after cesarean section.

OBJECTIVE: The goal of this study was to compare carbetocin, a long-acting oxytocin analog, with oxytocin in the prevention of uterine atony after cesarean section. STUDY DESIGN: We enrolled 694 patients undergoing elective cesarean section in a Canadian multicenter, double-blind, randomized clinical trial. We compared the effect of a single 100 microg dose of carbetocin with that of a standard 8-hour infusion of oxytocin. The primary outcome was the proportion of patients requiring additional oxytocic intervention for uterine atony. A variable sample size, sequential design was used. RESULTS: The overall oxytocic intervention rate was 7.4%. The odds of treatment failure requiring oxytocic intervention was 2.03 (95% confidence interval 1.1 to 2.8) times higher in the oxytocin group compared with the carbetocin group, respectively, 32 of 318 (10.1%) versus 15 of 317 (4.7%), P <.05. CONCLUSIONS: Carbetocin, a new drug for the prevention of uterine atony, appears to be more effective than a continuous infusion of oxytocin and has a similar safety profile.

Adult↗

Expression of the somatostatin receptor subtype-2 gene predicts response of human pancreatic cancer to octreotide.

BACKGROUND: Somatostatin inhibits proliferation of many solid tumors. The current study examines whether inhibition of the growth of pancreatic cancer by the somatostatin analog, octreotide, requires tumor expression of somatostatin receptors. METHODS: We studied five human pancreatic cancer cell lines, Capan-1, Capan-2, CAV, MIA PaCa-2, and Panc-1. Solid tumors were established in nude mice (n = 20/cell line) by flank injection of tumor cells. Subcutaneous octreotide (500 micrograms/kg/day) was administered by osmotic pumps to 10 of the animals in each group, and the other 10 received control infusions of saline solution. On day 36, the tumors were excised and weighed. Plasma levels of the putative trophic peptides cholecystokinin, epidermal growth factor (EGF), insulin-like growth factor-1 (IGF-1), and insulin were assessed by radioimmunoassay. Each of the five cell lines was assayed for the presence of cell surface somatostatin receptors by using whole cell competitive binding assays with 125I-somatostatin. Expression of the somatostatin receptor subtype-2 (SSR2) gene was determined with reverse transcriptase-polymerase chain reactions. Southern blot hybridization was used to assess the presence of the SSR2 gene. RESULTS: Octreotide inhibited tumor growth in the MIA PaCa-2 group (512 +/- 75 mg control versus 285 +/- 71 mg treated; p < 0.05) but had no significant effect on tumor weight in the other four cell lines. Plasma levels of cholecystokinin, epidermal growth factor, insulin-like growth factor-1, and insulin were not altered by chronic octreotide infusion. Cell surface somatostatin receptors and SSR2 gene expression were detected only in the MIA PaCa-2 tumors. The gene for the SSR2 receptor was found in all five tumor lines. CONCLUSIONS: Octreotide-mediated inhibition of pancreatic cancer growth is dependent on expression of somatostatin receptors. The expression of somatostatin receptors should be considered in the design and interpretation of clinical trials with somatostatin analogs for treatment of pancreatic cancer.

Adenocarcinoma↗

Chorionic villus sampling as the primary diagnostic tool in prenatal diagnosis. Should it replace genetic amniocentesis?

Recent studies in Canada and the United States have shown that chorionic villus sampling (CVS) is both safe and accurate, with a fetal loss rate likely slightly higher than that of amniocentesis but still at an acceptable level (1%). Although CVS may become the dominant prenatal diagnosis procedure, it is unlikely that it will completely replace amniocentesis. The two procedures are essentially complementary in the provision of prenatal diagnosis in the first and second trimesters.

Amniocentesis↗

Weights of fetuses with autosomal trisomies at termination of pregnancy: an investigation of the etiologic factors of low serum alpha-fetoprotein values.

In order to determine whether the low values of maternal serum alpha-fetoprotein observed with autosomal trisomies are associated with smaller fetal weights, 50 fetuses with Down syndrome (trisomy 21), 10 with trisomy 18, and 65 normal control fetuses, all aborted in the second trimester of pregnancy, were compared. The mean multiple of the median maternal serum alpha-fetoprotein was found to be 0.79 +/- 0.61 for fetuses with Down syndrome and 0.50 +/- 0.26 for those with trisomy 18, both results being significantly lower than results from the control fetuses (0.97 +/- 0.86). No significant difference in the weight distribution between fetuses with Down syndrome and control fetuses, corrected for gestational age, was found. By contrast, fetuses with trisomy 18 had a significantly lower weight distribution compared with that of the control fetuses (p less than 0.001). A linear relationship was found in normal fetuses between maternal serum alpha-fetoprotein values and fetal weight at a given gestational age. Fetal weight does not seem to account for the lower maternal serum alpha-fetoprotein levels seen in fetuses with Down syndrome but may partially account for the lower levels seen in fetuses with trisomy 18.

Abortion, Induced↗

Transabdominal chorionic villus sampling in the second trimester.

Transabdominal chorionic villus sampling under ultrasound guidance was carried out in 19 patients in the second trimester. We found that needle size combination 17/19 provided the best results with consistently adequate samples of tissue. Transabdominal chorionic villus sampling is a potentially useful technique for providing relatively rapid prenatal genetic diagnosis in patients at high risk in the second trimester.

Biopsy↗

Maternal serum alpha-fetoprotein screening: report of a Canadian pilot project.

A pilot project of maternal serum alpha-fetoprotein (MSAFP) screening was carried out in Ontario from 1982 to 1985 to examine the feasibility and acceptability of screening a prenatal population for open fetal neural tube defects. A total of 8140 patients at low genetic risk were screened. Patient acceptance was excellent. Blood samples were taken at 16 to 18 weeks' gestation. If the MSAFP level was elevated, the assay was repeated and an ultrasound examination performed. Amniocentesis was offered to 67 women with unexplained persistently elevated levels. The outcome of pregnancy was known in 7473 patients (91.8%). Seven of nine known open fetal neural tube defects were detected. All were confirmed, and no unaffected fetuses were aborted on the basis of the screening results. The rates of perinatal death (6.7%), intrauterine growth retardation (11.7%) and prematurity (23.3%) were significantly higher among the patients with unexplained elevated MSAFP levels than among those with normal levels (p less than 0.001). Of 20 patients with unexplained low levels, 10 subsequently had spontaneous abortions and 10 gave birth to term appropriate-for-gestational-age infants. Seven of nine patients who gave birth to infants with autosomal trisomy had MSAFP values below the median. The findings indicate that MSAFP screening is feasible, accurate and acceptable in a low-risk area.

Abortion, Spontaneous↗

Maternal serum alpha-fetoprotein and fetal autosomal trisomies.

Maternal serum alpha-fetoprotein values in 61 patients with fetal autosomal trisomies diagnosed at 6581 genetic amniocenteses were significantly lower than those in an equal number of matched control subjects. The genetic risk of fetal autosomal trisomies for women less than age 35 offered amniocentesis with maternal serum alpha-fetoprotein values less than 0.5 multiples of the median is in the same range as that currently accepted for advanced maternal age. Maternal serum alpha-fetoprotein screening for autosomal trisomies (mainly Down syndrome) is feasible.

Adult↗

Infant outcome following mid-trimester amniocentesis: development and physical status at age six months.

Ninety-one infants whose mothers had had amniocentesis, because age increased their risk for a fetal chromosome abnormality, were compared with 53 infants whose mothers chose not to have the test. Mental and motor development and temperament were studied to assess potential influence of amniocentesis on the brain. Physical growth was assessed and the infants were examined for orthopaedic abnormalities and needle injury. The results indicated that amniocentesis does not appear to influence infant mental and motor development, temperament, physical growth or the risk of orthopaedic abnormalities. However, amniocentesis is not entirely free of risk because several of the infants had needle marks. Reassessment of the cohort at age 4 and 7 years and will provide information on the potential longer term consequences of mid-trimester amniocentesis.

Adult↗

Midtrimester amniocentesis: obstetric outcome and neonatal neurobehavioral status.

The possible effects of midtrimester genetic amniocentesis on neurobehavioral status were studied in newborn infants of women who had had the procedure (N = 100) and in newborn infants of women who had declined the test (N = 56). Brazelton's Neonatal Behavioral Assessment Scale was administered to newborn infants born at term and did not reveal consequences of amniocentesis on neonatal orientation, range of state, motor ability, autonomic regulation, regulation of state, response decrement, or reflexes. Information on obstetric complications also was obtained. The findings raised questions regarding the temporal relationship between amniocentesis and fetal loss and focused attention on preterm birth as a potential risk that warrants further investigation. This study provides the foundation for our prospective longitudinal follow-up in which the cohort will be reassessed later in infancy and in childhood.

Adult↗

Genetic amniocentesis in seventy twin pregnancies.

Genetic amniocenteses were performed in 70 twin pregnancies over an 11-year period. Both sacs were successfully sampled in 49 of 62 patients (79%). The success rate was decreased (68%) with two placentas (anterior and posterior) and was improved with gestational age greater than or equal to 17 weeks (88%) and with ultrasound visualization of the septum (86%). Of three spontaneous abortions, two were attributed to amniocentesis (chorioamnionitis). When twin pregnancy is diagnosed in a patient with an indication for genetic amniocentesis, a careful reevaluation and discussion of risk factors with the couple are recommended.

Adult↗

A clinical approach to the use of predictive values in the prenatal diagnosis of neural tube defects.

The rationale of calculating predictive values to interpret the amniotic fluid alpha-fetoprotein (AFP) test has been examined and applied to amniotic fluid AFP testing from one Canadian center. Such predictive value ccalculations may be misleading if they fail to make use of the actual magnitude of the test result or the results of other investigations. The alculation of predictive values has thus been extended to take into account magnitude of the test results, the clinical history, and the results of other investigations. The interpretation of an abnormal amniotic fluid AFP test that is followed by a normal result of a careful ultrasound scan of the fetal back is that there is a 54.5% chance that the fetus has spina bifida if there is a previous history of spina bifida. There is a 12.5% chance if there is a negative family history. These calculations lead to informed genetic counseling and rational decision making with regard to the continuation of the pregnancy.

Amniocentesis↗

The effect of maternal steroid administration on fetal platelet count in immunologic thrombocytopenic purpura. Management of pregnancy and mode of delivery.

Eight pregnancies complicated by immunologic thrombocytopenic purpura are described and the literature is reviewed. We conclude that, while steroid treatment favorably influenced fetal platelet counts in our cases, overall experience with this disease indicates that such protection is incomplete in some cases and unnecessary in others. Antiplatelet antibody levels show promise as excellent indicators of fetal thrombocytopenia, and elevated levels may be an indication for steroid therapy for the improvement of fetal well-being in some cases.

Adrenal Cortex Hormones↗

Alpha-fetoprotein and ultrasound scanning in the prenatal diagnosis of Turner's syndrome.

Based on data from 5 cases of fetal cystic hygroma (4 cases of Turner's Syndrome and one case of Trisomy 18) and one case of Down's Syndrome with severe subcutaneous oedema, it is concluded that amniotic fluid alpha-fetoprotein (AFP) is normal or only slightly elevated in such cases whereas AFP in fluid from the cystic structures is very high. Reported high values of 'amniotic fluid' AFP are therefore likely to have been obtained from fluids accidentally drawn from the cystic structures. Fluids from the two sources cannot be distinguished from each other visually. In support of this theory is that the maternal serum AFP was found to be normal in all cases where investigated. In the diagnosis of cystic hygromata detailed ultrasound scanning will reveal the correct diagnosis.

Adult↗

Management of postoperative vaginal hemorrhage.

The authors' experience in the management of postoperative vaginal hemorrhage from 1975 to 1980 was reviewed. Recently, success has been achieved using angiographic arterial embolization with the Gianturco minicoil. The results of embolization are compared with those achieved through other more conventional methods. The authors have found angiographic embolization to be safe, simple, and effective, and they recommend that the procedure be performed before laparotomy for intractable postoperative vaginal bleeding.

Adult↗

Studies of an alpha-fetoprotein assay using dry blood-spot samples to be used for the detection of fetal neural tube defects.

We modified the Pharmacia serum alpha-fetoprotein (AFP) kit to enable its use with dry blood-spots on filter paper. Reference values were established for blood from 253 women in the 16th to 18th weeks of gestation. The result by the present technique in a woman with a confirmed anencephalic fetus was elevated, and in agreement with the results of AFP assays in serum and amniotic fluid. Blood AFP was stable on dried filter paper sent by mail.

Female↗

Ultrasound and amniotic fluid alpha-fetoprotein in the prenatal diagnosis of spina bifida.

Amniotic fluid alpha-fetoprotein (AFP) assays and detailed ultrasound examinations were performed in 376 prenatal patients at risk for a neural tube defect (high-risk group). In addition, 2436 patients who underwent amniocentesis for other indications underwent preamniocentesis ultrasound screening and amniotic fluid AFP assays (low-risk group). There were 10 neural tube defects in the high-risk group (7 open and 3 closed) and 3 in the low-risk group (all open). Two of the 3 closed defects were detected prenatally. The predictive value of an elevated AFP level for an abnormal fetus was much higher in the high-risk (6 of 6, 100%) than in the low-risk group (1 of 6, 17%). When both ultrasound and AFP assay results were normal, the chance of a normal outcome was very high in both the high- and low-risk groups (99.7 and 100%, respectively). It was of particular interest that in the low-risk group, the likelihood of an abnormal outcome in women with elevated AFP and a normal ultrasonogram was low (0 of 5).

Amniocentesis↗