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Biomedical subjects

J F O'Connor

Publications and source records attributed to J F O'Connor.

At least 19 recordsLinked to original sources

Choriocarcinoma-like human chorionic gonadotrophin (HCG) and HCG bioactivity during the first trimester of pregnancy.

The objective of this study was to evaluate the distribution of choriocarcinoma-like human chorionic gonadotrophin (HCG) isoforms during first trimester pregnancy and their relationship with in-vitro HCG bioactivity. This was done by means of a retrospective analysis of patients' sera with first trimester normal intrauterine and abnormal (ectopic) pregnancies. Serum samples were obtained from 38 women with an amenorrhoea of <10 weeks. From these, 19 had a normal intrauterine pregnancy (IUP) and 19 an ectopic pregnancy (EP). Total immunoreactive HCG (HCGi), free beta-HCGi and oestradiol were measured by enzyme immunoassays and bioactive HCG by the mouse Leydig cell bioassay. The alterations in HCG isoform content were measured by the combination of two immunometric assays, B152 for choriocarcinoma-like HCG and B109 for intact HCG detection and expressed as the B152/B109 ratio. Choriocarcinoma-like HCG isoforms ratio measured by B152 and B109 assays was significantly higher in the low subgroups of free beta-HCGi and gestational age (P = 0.0111 and 0.0036 respectively). Whereas bioactive to immunoreactive HCG ratios (b/i ratio) were significantly higher when free beta-HCGi concentrations were low (P = 0.0010), no correlation was found between the variation of bioactivity (b/i ratio) and the proportion of choriocarcinoma-like HCG isoforms (B159/B108). It is concluded that in first trimester pregnancies (i) the modulation of HCG in-vitro bioactivity is not related to the variation of choriocarcinoma-like HCG isoforms secretion and (ii) the amount of choriocarcinoma-like HCG isoforms secreted by the early trophoblast is predominant and may be the result of an early developmental regulation of glycosylation enzyme.

Amenorrhea↗

The cost-effectiveness of strategies to assess gastroesophageal reflux as an exacerbating factor in asthma.

OBJECTIVES: We sought to evaluate the cost-effectiveness of diagnostic strategies to determine whether or not acid reflux exacerbates asthma, and to identify which asthma response probabilities are most important in a cost-effective workup of this problem. METHODS: We performed a cost-effectiveness analysis, comparing 11 diagnostic strategies to assess the role that acid reflux plays in asthma. Probabilities and costs were derived from the published literature. Average and incremental costs, effectiveness, and cost-effectiveness were calculated for each strategy. Sensitivity analyses were performed. RESULTS: The most cost-effective diagnostic approach is to begin with omeprazole 20 mg/day for 3 months, followed by 24-h pH testing on drug in nonresponders. If 24-h pH testing is positive, increase the omeprazole dose every 3 months until the patient responds or a maximum of 60 mg/day is given. This strategy costs $730 per case correctly diagnosed. When the cost of pH testing exceeds $586 or the cost of omeprazole 20 mg/day is <$53 per month, omeprazole 20 mg/day for 3 months followed by 60 mg/day for the same duration in nonresponders becomes more cost-effective. CONCLUSIONS: Empiric acid reflux suppression, followed by pH testing in nonresponders, is the most cost-effective means of determining whether GERD is aggravating a patient's asthma.

Asthma↗

Early pregnancy human chorionic gonadotropin (hCG) isoforms measured by an immunometric assay for choriocarcinoma-like hCG.

Human chorionic gonadotropin (hCG) exhibits molecular heterogeneity in both its protein and carbohydrate moieties. This communication describes changes in hCG isoforms detected directly in clinical samples. These isoforms, quantified in blood or urine specimens, show a progression of change throughout normal pregnancy. Early pregnancy produces a type of hCG that resembles, in terms of immunoreactivity, a major form of hCG excreted in choriocarcinoma. The isoforms predominate for the first 5-6 weeks of gestation and then diminish, being replaced with the hCG isoforms which predominate throughout the remainder of pregnancy. The alteration in hCG isoform content occurs in both blood and urine. The progression of isoforms is best delineated by calculating the change in the ratio of the two forms, as many hCG assays either do not detect or fail to discriminate among these isoforms. An analogous pattern of hCG isoforms was observed in patients with in vitro fertilization pregnancies. hCG isolated from the pituitary displayed binding characteristics similar to those of the hCG derived from normal pregnancy urine. The early pregnancy hCG isoforms appear to have a differential expression in normal pregnancy as opposed to pregnancies which will not carry to term, suggesting that a determination of the relative balance of hCG isoforms may have diagnostic application in predicting pregnancy outcome.

Biomarkers↗

Evaluation of nicked human chorionic gonadotropin content in clinical specimens by a specific immunometric assay.

We report the development and characterization of an IRMA for the direct measurement of nicked human chorionic gonadotropin (hCGn) in blood and urine. hCGn derived from a reference preparation of hCG used as an immunogen elicits monoclonal antibodies (mAbs) with enhanced recognition of human luteinizing hormone epitopes. The most specific assay for pregnancy hCGn is an IRMA composed of one mAb to choriocarcinoma-derived hCGn (C5) and a second mAb developed from immunization with normal-pregnancy hCGn. This assay was used to evaluate hCGn profiles in normal, in vitro fertilization, Down syndrome, and ectopic pregnancies. In all pregnancies, hCGn was usually present in much lower concentrations than the non-nicked hCG isoform. Our results suggest that some form of physical separation from the overwhelming quantities of non-nicked hCG present in clinical specimens will be required before accurate immunochemical estimations of hCGn can be made.

Abortion, Spontaneous↗

Differential urinary gonadotrophin profiles in early pregnancy and early pregnancy loss.

Early pregnancy loss (EPL), detected by patterns of human chorionic gonadotrophin (hCG) in urine, is the biomarker employed in investigations of the impact of personal, workplace or environmental reproductive toxins on human fertility. An issue central to these studies is what, in terms of urinary hCG expression, constitutes an EPL. This report describes the urinary molecular forms of hCG expressed in menstrual cycles in which a normal pregnancy was conceived, or an EPL occurred, or no apparent conception occurred. Qualitative and significant quantitative differences in the expression of hCG-associated analytes were found between normal pregnancy cycles and EPL cycles. Discriminant analysis calculation based on mole fractions of the different hCG-associated molecules afforded 91 per cent and 80 per cent correct classification of clinical pregnancy cycles and EPL cycles, respectively. Although hCG-associated molecules unique to either EPL or normal pregnancy were not found, what is thought to be an early form of hCG is expressed both at a high frequency and at a significantly higher concentration in early normal pregnancy when compared with EPL. The relative absence of this molecule very early in pregnancy may signal a pregnancy loss.

Abortion, Spontaneous↗

Fluoroscopic examination in the neonatal intensive care unit using an inverted C-arm.

Fluoroscopic studies can be performed in the Neonatal Intensive Care Unit (NICU) using a portable C-arm. The C-arm is inverted so that the infant lays directly on the image intensifier. In all our cases, the images obtained were of good enough quality to allow for prompt diagnosis and management of the patient's condition. Furthermore, measured entrance doses were lower using the inverted C-arm than they were using conventional fluoroscopy.

Fluoroscopy↗

Measuring human chorionic gonadotropin in the absence of implantation with use of highly sensitive urinary assays for intact beta-core and free beta epitopes.

OBJECTIVE: To determine if human chorionic gonadotropin (hCG) can be absorbed from the uterine cavity in the absence of an embryo. DESIGN: Prospective study. SETTING: University-based assisted reproduction program. PATIENT(S): Eight functionally agonadal patients (age range, 33-46 years) who were taking hormone replacement therapy so that they could receive donated oocytes. INTERVENTION(S): Intrauterine instillation of 50 microL of hCG (10,000 IU) during a mock cycle before an attempt at oocyte donation. MAIN OUTCOME MEASURE(S): Spot urine measurements of different hCG epitopes (intact beta, beta-core, and free beta) at timed intervals (12, 20, 44, and 68 hours after instillation). RESULT(S): All hCG epitopes were detected in the urine at the first sampling interval, and levels decreased in subsequent sampling intervals. Measurement of the serum hCG level confirmed that systemic absorption had occurred and that the urine measurements were not a result of specimen contamination through the cervix. CONCLUSION(S): hCG may be systemically absorbed into the blood through the uterine cavity, even in the absence of implantation, and its metabolites may be measured with use of highly sensitive urinary assays.

Adult↗

Detecting pre-ovulatory luteinizing hormone surges in urine.

The study objectives were to determine (i) if pre-ovulatory luteinizing hormone (LH) surges, undetected in urine by two immunoradiometric assays (IRMA), were detectable by an ultrasensitive immunofluorometric assay (IFMA) and (ii) the influence of creatinine adjustment on the detection and timing of the urinary LH surges. Daily urine specimens were contributed by healthy 25-36 year old volunteers during 14 ovulatory menstrual cycles for an epidemiological study conducted in 1983-1985. Specimens were selected as having been previously assayed by two IRMA without consistently detecting LH surges. These urine specimens were remeasured using an IFMA and adjusted for creatinine concentration. IFMA measurements revealed unambiguous LH surges in all cycles. Adjusting IRMA urinary LH values for creatinine concentrations revealed previously undetected LH surges in four of eight cycles. Creatinine adjustment also altered the timing of IRMA and IFMA LH surges by 1-5 days. These results demonstrate an IFMA that detects pre-ovulatory LH surges in unpreserved, frozen urine from cycles where such surges were previously undetectable. Further, creatinine adjustment can markedly affect detection and timing of the onset and peak of the urinary LH surge. While our analysis suggests that this adjustment improves the validity of the LH measure, this requires further investigation.

Adult↗

The expression of the urinary forms of human luteinizing hormone beta fragment in various populations as assessed by a specific immunoradiometric assay.

Human gonadotrophins undergo metabolic transformations which result in the presence of several smaller, structurally and immunologically related forms of gonadotrophins in the urine. For luteinizing hormone (LH), a beta core fragment (LHbeta cf) has been isolated from the pituitary and characterized. The corresponding urinary fragment is inferred from mass spectral and immunochemical analysis of chromatographically separated urinary forms. Physicochemical characteristics, primarily mass spectral and chromatographic, indicate that the pituitary and urinary forms of LHbeta cf have a different structure, probably in the carbohydrate moieties. This communication characterizes the expression of LHbeta cf in the urine of both reproductive and post-reproductive age women and in men, employing assays highly specific for the pituitary form of the fragment. It was found that LHbeta cf is the predominant LH associated molecular form in the urine during peri-ovulatory period, peaking 1-3 days later than intact LH and reaching a concentration of approximately 600 fmol/mg creatinine, 7-fold higher than either LH or LH free beta subunit. Corresponding concentrations of human chorionic gonadotrophin (HCG) beta cf were <1% that of LHbeta cf. LHbeta cf cross-reaction with some LH or LHbeta monoclonal antibodies may well interfere with the accurate estimation of the day of the LH surge when urinary tests are utilized.

Adolescent↗

Alcoholic liver disease: proposed recommendations for the American College of Gastroenterology.

OBJECTIVE: The objective of this work was to develop practice guidelines for the management of alcoholic liver disease. METHOD: A computerized search using the Medline Data Base from 1966-July 1997 was performed with the search headings; alcohol, alcoholic hepatitis, alcoholic liver disease, liver transplant, diagnosis, epidemiology, human, and English only. All randomized controlled trials, case-control studies, and meta-analyses were read in depth. A manual search was also done using references from each retrieved report, review articles, editorials, postgraduate course syllabi, and textbooks. In the subsequent review, evidence was evaluated using a hierarchical scale with randomized, controlled trials given the most importance. Abstracts presented at national meetings were included only when unique data were obtained from those studies.

Humans↗

Characterization of human chorionic gonadotropin peptide variants with a radio-receptor assay using recombinant human luteinizing hormone/chorionic gonadotropin receptors.

There are potential interactions between various human chorionic gonadotropin (hCG) isoforms at the level of luteinizing hormone/chorionic gonadotropin (LH/CG) receptor. The objective of this study was to characterize the receptor-binding activities of the primary peptide variants of hCG including intact hCG, free beta subunit, beta-core fragment and nicked hCG, and to test the effects of these hCG variants on the binding of intact hCG. A radio-receptor assay based on cell membranes expressing recombinant human LH/CG receptors was validated and used in this study to avoid species differences in the receptor-binding specificity. The results showed that none of the hCG variants that we studied had sufficient binding affinity to compete with binding of intact hCG, nor were they able to antagonize the binding of intact hCG. These results suggest that hCG variants with either abbreviated polypeptide structures or incomplete peptide linkage are products or metabolites which do not have the tropic biological activity of the whole hormone, the intact heterodimeric hCG.

Cells, Cultured↗

Characterization of human chorionic gonadotropin in normal and abnormal pregnancies.

In this study circulating human chorionic gonadotropin (hCG) levels in the peri-implantation period of natural cycles of normal women were characterized. The hypothesis that the bioactivity of hCG in abnormal pregnancies is different from that in normal pregnancies was tested daily through serum hCG measurements in two immunoenzymometric assays, a radioreceptor assay and a human luteinizing hormone/human chorionic gonadotropin--cyclic adenosine monophosphate--luciferase bioassay. In normal pregnancies, the levels of immunoreactive and bioactive hCG were higher than in abnormal pregnancies (p < 0.05). In addition, the slopes of the rise in concentration of hCG as measured in all four assays were significantly greater for normal pregnancies than for abnormal pregnancies (p < 0.01). The rate of rise of hCG bioactivity was significantly greater than the rise of immunoreactivity or receptor-binding activity in normal pregnancies, but this difference was not observed in abnormal pregnancies. These results indicate that: (1) A steep rise of bioactive hCG is a consistent feature of the peri-implantation period of normal pregnancies. (2) Abnormal pregnancies had a deficiency in the production of hCG, which was reflected in both the hCG levels and the rate of increase, even in the first week of implantation. (3) Some abnormal pregnancies produced hCG with lower biological activity than the hCG of normal pregnancies.

Abortion, Spontaneous↗

Mallet finger.

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Finger Injuries↗

The rise and fall of a radiologic technique.

As young radiologists read the slightly self-satisfied articles celebrating the centennial of radiology, they may conclude that the course of radiology and all its components has been smoothly upward, without hesitations, false starts, or disappointments. Older radiologists know better. The replacement of a less satisfactory technique with a better one is a gain for both patients and physicians, but the replacement process itself can be distressing. Much of what radiology residents learned in the 1950s and 1960s is no longer of any use. Who now employs pneumoencephalography or intravenous cholangiography? Entire books were once written about these procedures [1, 2]. Who can now credit the reliance once placed on positive-contrast maxillary antrography [3]? Few have even heard of eustachian tubography [4]. Radiologists who tried to make a career using those techniques learned to their sorrow that although anatomy is permanent and diseases change only slowly, techniques are often ephemeral. Total body opacification, a technique once of consuming interest to the present writers [5-7], is an illustration of this.

History, 20th Century↗