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Biomedical subjects

J A Collins

Publications and source records attributed to J A Collins.

At least 19 recordsLinked to original sources
PubMed1992

Intratumoral and whole-body distributions of C110 anti-carcinoembryonic antigen radioimmunotoxin after intraperitoneal and intravenous injection: a quantitative autoradiographic study.

The intratumoral and whole-body distributions of 90Y-labeled C110 anticarcinoembryonic antigen immunotoxin after i.p. and i.v. injection were compared by quantitative autoradiography. During in vitro incubation of spherical tumor nodules of LS174T human colon cancer (about 5 mm in diameter) in a medium containing C110 radioimmunotoxin (RIT), the direct penetration of the immunotoxin increased with time but was limited to the outer 300 microns of the tumor nodule after 12 h of incubation. In vivo experiments were performed in nude mice bearing LS174T xenografts as i.p. tumor nodules. Injection of C110 RIT i.p. resulted in a ring-like distribution, i.e., high uptake at the tumor periphery and considerably lower uptake at the tumor center (ratio of peripheral to central concentration, 7:1 at 1 day and 2:1 at 5 days). In contrast, i.v. injection provided a much smaller gradient in C110 RIT distribution from peripheral to central regions (ratio of peripheral to central concentration, 3:1 at 1 day and 1:1 at 5 days). Estimates of total tumor uptake of C110 RIT by quantitative autoradiography demonstrated almost equivalent tumor uptake after either i.p. or i.v. injection, while i.v. injection was associated with increased C110 RIT uptake in various normal organs, especially in the liver, as compared to i.p. injection. The results in this study suggest that (a) i.v. injection may produce more homogeneous distribution of C110 RIT in i.p. tumor nodules of LS174T but may also result in increased liver toxicity, and (b) i.p. injection may decrease C110 RIT exposure of normal tissues, which can reduce systemic toxicity, but may also produce more restricted intratumoral distribution of C110 RIT. In addition, current methods using a nude mouse model of i.p. tumor nodules and quantitative autoradiography allow us to assess intratumoral and whole-body distributions of radiolabeled immunoconjugates from various administration routes.

Animals↗
PubMed1992

A comparison of ovulation suppression and ovulation stimulation in the treatment of endometriosis-associated infertility.

This study compares ovulation stimulation or suppression with the pregnancy rate among infertile couples with endometriosis. The design is a nonrandomized, prospective, multicentered cohort analytic study. Two hundred and ninety-seven couples with laparoscopy-proven endometriosis were analyzed: 68 received no therapy, 42 received clomiphene and 74 received danazol. Forty patients (22%) conceived and pregnancy rates were similar in each treatment group. The relative likelihood of pregnancy associated with clomiphene was 2.9 (95% confidence limits 1.2-7.1); the relative likelihood of pregnancy with danazol was 1.02 (95% confidence limits 0.5-2.3). This study suggests that pregnancy rates during clomiphene treatment could be superior to expectant therapy, while pregnancy rate after danazol is similar to no treatment.

Adult↗
PubMed1992

Unexplained infertility: a review of diagnosis, prognosis, treatment efficacy and management.

The dilemma of unexplained infertility posed by Southam in 1960 remains today: despite advances in the diagnostic assessment of infertility, many couples still have no explanation for their infertility. Even the most sophisticated evaluation of semen, ovulation and genital tract competence cannot reveal all of the possible defects in the complex process leading to conception. Because it arises from these shortcomings in our knowledge of fertilization and from our inability to utilize all of the current knowledge, unexplained infertility is a challenge for both biological and clinical research. This paper attempts to summarize some clinical issues in the management of unexplained infertility: the prevalence of the disorder, problems in the definition and possible explanations for the existence of this diagnostic category. It reviews outcome-based clinical publications as a guide to decision-making on what diagnostic tests to use, provides a summary of the untreated prognosis and evaluates study results that may serve as a basis for treatment decisions in this puzzling diagnostic category of infertility.

Age Factors↗
PubMed1992

The routine use of gonadotropin-releasing hormone agonists prior to in vitro fertilization and gamete intrafallopian transfer: a meta-analysis of randomized controlled trials.

OBJECTIVE: To assess the efficacy of gonadotropin-releasing hormone agonists (GnRH-a) used in ovulation induction for in vitro fertilization and embryo transfer (IVF-ET) and gamete intrafallopian transfer (GIFT). DESIGN: Meta-analysis of 10 trials comparing treatment cycle outcomes after GnRH-a (n = 914) with other ovulation induction protocols (n = 722) and 7 trials comparing outcomes after short flare-up (n = 368) with longer suppression (n = 476) GnRH-a protocols. MAIN OUTCOME MEASURES: The outcome of primary interest was clinical pregnancy rate (PR) per treatment cycle commenced. Data describing the amount of gonadotropin used, cycle cancellation rate, clinical pregnancy per ET, and multiple pregnancy and abortion rates were also analyzed. RESULTS: Clinical PR per cycle commenced was significantly improved after GnRH-a use for IVF (common odds ratio [OR] 1.80, 95% confidence interval [CI] 1.33 to 2.44) and GIFT (common OR 2.37, 95% CI 1.24 to 4.51). Clinical PR per embryo transfer was also significantly improved with GnRH-a use (common OR 1.40, 95% CI 1.01 to 1.95). Cycle cancellation was decreased (common OR 0.33, 95% CI 0.25 to 0.44), whereas spontaneous abortion rate was similar with and without GnRH-a use. Cycle cancellation and PRs after short flare-up and longer suppression protocols were similar between groups. CONCLUSIONS: This meta-analysis supports the routine use of GnRH-a for IVF and GIFT. Further research is needed, however, to assess the potential for increased rates of multiple pregnancy and ovarian hyperstimulation syndrome, which may be associated with this treatment.

Abortion, Spontaneous↗
PubMed1992

Prognostic factors in assessment and management of male infertility.

Evaluation of 304 infertile couples with at least one abnormal semen analysis (sperm density < 20 x 10(6)/ml and/or motility < 50%) and no apparent female factors was performed in a multicentre prospective cohort study. In 73 cases therapeutic donor insemination was performed (TDI group) with a resulting pregnancy rate of 48%. The remaining 231 couples (non-TDI group) had an overall pregnancy rate of 25%. The TDI group had a shorter duration of infertility. The ages of both partners were comparable in TDI and non-TDI groups. In the non-TDI group, univariate analysis resulted in identification of six clinical variables associated with a change in pregnancy rates. The strongest association was noted for length of infertility. There was a weaker association for semen volume, concentration of leukocytes in semen, history of pregnancy in the female partner and laparoscopy. Multiple variable analysis of data from the non-TDI group revealed that independent predictors of pregnancy were 'duration of infertility' and 'history of pregnancy in the female partner'. The multiple variable modelling suggested that (i) an increase in the length of infertility by 1 month prolongs the time to pregnancy by an additional 1.6% (95% confidence interval: 1.5-1.7%); and (ii) a history of past pregnancy in the female partner reduces the time of pregnancy by 51% (95% confidence interval: 47-56%).

Female↗
PubMed1992

Thromboembolism following multiple trauma.

The true incidence of thromboembolic complications following multiple trauma is unknown, and no method of prophylaxis has been shown to be both safe and effective in managing seriously injured patients. In this prospective study, 113 trauma patients were assigned on admission to receive either low-dose heparin (LDH), (5,000 U subcutaneously every 12 hours) or to wear sequential compression devices (SCDs) as prophylaxis against the development of deep venous thrombosis (DVT). Both groups of patients were serially studied with duplex venous ultrasound imaging to detect thrombus in the veins of the thigh. Ventilation-perfusion lung scans and pulmonary angiograms were performed when pulmonary embolism (PE) was suspected clinically. There were 12 patients who had thromboembolic complications, including 9 of 76 in the SCD group (12%) and 3 of 37 in the LDH group (8%). Five patients had DVT only, four had PE without detectable DVT, and three had both DVT and PE. None of the patients with PE died, and there were no major complications associated with either method of prophylaxis. Compared with the patients who did not develop DVT/PE, those with thromboembolic complications were older (49 +/- 23 vs. 36 +/- 17 years, p less than 0.02), spent more hospital days immobilized (24 +/- 15 vs. 10 +/- 13 days, p less than 0.001), received more transfusions (11 +/- 12 vs. 3 +/- 5 U, p less than 0.001) and had clotting abnormalities on admission, as demonstrated by prolonged PTT values (39 +/- 28 vs. 26 +/- 5 seconds, p less than 0.001). It appears that there is an identifiable subgroup of injured patients at highest risk for PE who warrant both prophylaxis and close surveillance for DVT.

Adolescent↗
PubMed1991

Preclinical assessments of 90Y-labeled C110 anti-carcinoembryonic antigen immunotoxin: a therapeutic immunoconjugate for human colon cancer.

We have synthesized 90Y-labeled immunotoxin (IT) containing ricin A chain and C110 anti-carcinoembryonic antigen monoclonal antibody (MAb) to produce a therapeutic immunoconjugate for human colon cancer. The C110 IT was labeled with 90Y via a benzylisothiocyanate derivative of diethylenetriaminepentaacetic acid. The efficiency of 90Y labeling was consistently 90 to 98%, with a specific activity of about 1 microCi/microgram. In in vitro stability studies, more than 80% of 90Y remained bound to the C110 IT for up to 5 days after incubation. The percentage of binding of 90Y-labeled C110 IT to carcinoembryonic antigen-coated microbeads was 86%, indicating good retention of the initial immunoreactivity of the C110 MAb. In in vitro protein synthesis inhibition assays, 90Y-labeled C110 IT was approximately 3.7-fold more toxic to the LS174T human colon carcinoma cell line than unmodified C110 IT and 1380-fold more toxic than 90Y-labeled C110 MAb. Biodistribution studies of 90Y-labeled C110 IT in LS174T tumor-bearing mice showed that, at 24 h following i.p. injection, high accumulation of radioactivity was seen in the i.p. tumor and liver and, thereafter, high accumulation in these tissues remained almost unchanged until up to 168 h, with percentage of injected dose/g ranging from 15 to 18% in the tumor and 10 to 15% in the liver. The radioactivity in the spleen and bone gradually increased with time and reached their highest levels (approximately 8% of injected dose/g) at 168 h. Estimation of absorbed radiation doses to the tissues showed that i.p. tumor would have received an approximately 1.5 to 7 times higher radiation dose than normal organs. In in vivo therapeutic trials, 90Y-labeled C110 IT provided survival prolongation of LS174T tumor-bearing mice superior to that with either unmodified C110 IT or 90Y-labeled C110 MAb (4 less than 0.01; Mann-Whitney U test). These results indicate that 90Y-labeled C110 anti-carcinoembryonic antigen IT may be a potent therapeutic immunoconjugate for human colon cancer and that it may have direct relevance for i.p. treatment of peritoneal carcinomatosis from colon cancers.

Animals↗
PubMed1991

Use of prescription drugs in the first trimester and congenital malformations.

A prospective survey of prenatal use of prescription drugs in Tasmania yielded detailed information on drug exposure, delivery and outcome for 56,037 births from 1982 to 1989. First trimester drug use was reported by 30.9% of women, and 17.9% used only supplements of vitamins and/or minerals; 40% used alcohol during the first trimester, and 28.8% smoked cigarettes. There were 1,035 (1.85%) congenital malformations, of which 885 (85.5%) were major. The malformation rate was not significantly different in the following exposure categories: supplements only (1.62%); other pharmaceuticals (1.92%); smokers (1.88%); alcohol users (1.89%); and maternal age 35 or more years (1.95%). Adjusting for alcohol use, smoking, maternal age and diabetes mellitus, significant associations [expressed as adjusted odds ratio and 95% confidence intervals (CI)] were found between aspirin and hypospadias (3.5, 95% CI 1.4 to 8.8); dicyclomine and phocomelia (4.4, 95% CI 1.0 to 19.5); and between oral contraceptive use and pes cavus (9.7, 95% CI 2.3 to 40.4). Although significant, these associations were based on very few cases and no direct supporting evidence could be found from other data sources.

Abnormalities, Drug-Induced↗
PubMed1991

Initial clinical study of indium-111-labeled clone 110 anticarcinoembryonic antigen antibody in patients with colorectal cancer.

A murine monoclonal antibody directed against carcinoembryonic antigen (CEA) was labeled with indium-111 (111In) by means of a benzylisothiocyanate derivative of diethylenetriamine penta-acetic acid (DTPA) and used for clinical radioimmunodetection studies. Twenty-one patients having a history of surgically resected colorectal cancer and rising serum CEA levels suggestive of tumor recurrence were studied. Patients were infused over 20 minutes with 5, 10, or 20 mg of the monoclonal antibody labeled with 5 mCi of 111In. The mean radiochemical purity was greater than 96%. No toxicity was seen. The stability of the radiolabel on antibody in patient serum was demonstrated by high-performance liquid chromatography (HPLC), sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) with autoradiography, and immunoprecipitation for up to 96 hours after infusion. Tumor sites were identified in 20 of 21 patients. Sites of antibody accumulation in 20 patients were confirmed as tumor either by resection at laparotomy (16 patients) or fine-needle biopsy (four patients). Nine patients who had the identified lesion resected or irradiated showed return of the serum CEA antigen level to normal or near normal values. In the absence of high levels of circulating CEA (greater than 500 ng/mL), the disappearance of radioactivity from patient serum demonstrated first order elimination kinetics, with a mean half-life of 38 hours. The serum half-life was not affected by the dose of antibody administered or by serum CEA titers below 500 ng/mL. Despite a mean liver uptake of 18% injected dose (ID) 24 hours after administration, hepatic metastases were easily visualized as areas of increased uptake of radioactivity. Radioimmunodetection of recurrent colorectal cancer, not detected by computed tomographic (CT) scans, appears achievable with this agent. This may allow successful clinical intervention in selected patients.

Adult↗
PubMed1991

Performance and fecal flora of calves fed a Bacillus subtilis concentrate.

Eighty-four Holstein calves were assigned at 2 d of age to one of three treatments: 1) control with no additives; 2) 10 g of a mixed microbial concentrate containing Lactobacillus acidophilus, Lactobacillus lactis, and Bacillus subtilis; or 3) 10 g of a B. subtilis concentrate. The microbial concentrates were mixed with milk replacer during the a.m. feeding. The milk replacer was offered twice daily at 5% BW per feeding; the reconstituted replacer contained 12.5% DM. Volume of replacer fed was based on initial weight of calf and held constant until weaning. Water and starter ration were offered for ad libitum intake throughout the trial. Calves were weaned abruptly at 30 d of age and received only water and starter from d 31 to 44. General health and performance of all calves were good. Although differences in weight gain and feed efficiency were not significant, the B. subtilis concentrate tended to have a positive effect on feed efficiency during wk 1 to 4 and on immediate postweaning gain. A higher fecal bacilli count at 6 wk in calves fed the microbial concentrates may be related to their tendency for improved gain during d 31 to 44, the immediate postweaning period.

Animals↗
PubMed1990

Treatment-dependent and treatment-independent pregnancy among women with periadnexal adhesions.

In an attempt to evaluate the efficacy of salpingoovariolysis we studied 147 women who were found to have periadnexal adhesions on laparoscopic examination. Among these women, 69 were treated by laparotomy and salpingoovariolysis and 78 were not treated. There was no significant difference between the degree of adhesions in the treated group and in the nontreated group. With the use of life table analysis, the cumulative pregnancy rate at 12 and 24 months follow-up was 32% and 45% in the treated group and 11% and 16% in the nontreated group, respectively (p less than 10(-6)). We suggest that although pregnancy might occur in infertile women who have periadnexal adhesions, treatment with salpingoovariolysis is associated with a higher pregnancy rate.

Adnexal Diseases↗
PubMed1990

The value of semen analysis and sperm function assays in predicting pregnancy among infertile couples.

Over a 2-year period, 227 couples were evaluated by an extended assessment of the male partner's ejaculate. This extended assessment comprised sperm penetration of denuded hamster oocytes, ability of sperm to penetrate synthetic mucus, and the adenosine triphosphate (ATP) content of whole semen. In proportional hazards analysis adjusting for the contribution of clinical and other seminal variables, the sperm penetration assay (SPA) test was a predictor of pregnancy in the subgroup with normal conventional seminal variables (greater than 40 million motile sperm per ejaculate). When the SPA result was 20% or more the probability of pregnancy was 3.7 times higher; the performance of the SPA as a diagnostic test was better in the couples with treated tubal disease than in other diagnostic categories.

Acrylamides↗
PubMed1989

Unexplained infertility: evaluation of treatment with clomiphene citrate and human chorionic gonadotropin.

A double-blind, randomized, prospective therapeutic trial was conducted in 148 couples with unexplained infertility. Treatment consisted of 4 consecutive months of placebo or clomiphene citrate (CC) (100 mg) by mouth on cycle days 5 to 9, and placebo or human chorionic gonadotropin (hCG) (5,000 IU) intramuscularly on cycle days 19, 22, 25, and 28. There were 14 pregnancies during the trial and 39 pregnancies during observation before and after the trial. Placebo treatment resulted in no pregnancies over 4 months. Clomiphene citrate was significantly better than placebo (P less than 0.04), with a pregnancy rate of 19% over the course of 4 months. The pregnancy rate with hCG either alone (11%) or in combination with CC (7.6%), was not significantly better than placebo. Treatment-independent pregnancies, defined as those before treatment (but after enrollment), or more than 1 month after therapy, occurred in 16% of the couples, with a mean time to conception of 8.8 months. As part of their follow-up, 39 of the study couples subsequently underwent in vitro fertilization (IVF), and 43% were found to have a previously unrecognized male factor or fertilization defect. A pregnancy rate of 16% was achieved after a mean of 1.1 cycles in these 39 couples. The authors conclude that CC is useful in treating unexplained infertility and is a reasonable initial therapy. For couples who fail to conceive, IVF may be diagnostic as well as therapeutic.

Adult↗
PubMed1989

Age of the female partner is a prognostic factor in prolonged unexplained infertility: a multicenter study.

Among 2,106 couples registered in 12 Canadian infertility clinics, 470 (22.3%) were classed as unexplained infertility after a uniform evaluation of the male ejaculate, ovulation, and tubal patency. The unexplained group included more older female partners; 44% were over 30 years of age at registration in the participating clinics, compared with 36% in other infertility diagnostic groups. The mean duration of infertility was 40.1 months, and the cumulative pregnancy rate was 36.6 +/- 2.9% at 2 years after registration. When the variables were examined with the use of proportional hazards analysis, each additional month of duration of infertility reduced the expected prognosis by 2%, and a history of pregnancy in the partnership improved the prognosis by 80%. Among couples with 3 years or more duration of infertility (cumulative pregnancy rate, 27.5 +/- 3.9%), an additional year in the age of the female partner when conception was first attempted (mean, 26.8 years) reduces the prognosis by 9%.

Adult↗