A deleted B chromosome in a mosaic mother and her cri du chat progeny.
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Biomedical subjects
Publications and source records attributed to J Philip.
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Meiotic chromosomes of six mice injected with high doses of lysergic acid diethylamide (LSD-25) and of six controls were studied. Several breaks, gaps, and unidentifiable fragments were found in the treated but, with a few exceptions, not in the control animals. Secondary constrictions were more numerous in the treated than in the untreated mice. Possible consequences are discussed.
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Forty-seven twin pregnancies among 3676 patients who had a genetic amniocentesis between 1973 and 1979, are reported. The detection rate of twins at the time of amniocentesis was 62 per cent. Five (17 per cent) of the 29 women with detected twin pregnancy aborted spontaneously, these are compared with 1 (6 per cent) of 18 women with undetected twin pregnancies and with 3 (3 per cent) of 93 singleton pregnancies, selected as controls as they had amniocentesis performed immediately before and after each of the twin mothers. Two of 9 (22 per cent) twin pregnancies, who had at least two punctures in at least one sac aborted, while 3 of 20 twin pregnancies with one puncture in each sac aborted (15 per cent). One of 18 (6 per cent) twin pregnancies, where only one sac was punctured, because the twin pregnancies were undetected, aborted. Amniocentesis of both sacs in twin pregnancies seems associated with an increased risk of spontaneous abortion. The indications for amniocentesis in twin pregnancies should be critically evaluated.
A new culture vessel for amniotic fluid culture is presented (flaskette). It consists of a microscope slide, on top of which a culture chamber is mounted. Amniotic fluid cell cultures using in situ technique in the flaskette were compared to subcultured samples in ordinary (Falcon) tissue culture bottles. Working time was reduced by using this new culture vessel because of a very simple harvest procedure, allowing simultaneous harvest of 15 samples. The interval between amniocentesis and harvest was shorter for the in situ technique than for the subcultivation technique. The frequency of aneuploidy in individual metaphases was higher with the subcultivation technique, while there was no difference in the frequency of structural anomalies.
Citrullinaemia was presumed to be excluded in a fetus at risk by the direct assay of argininosuccinate synthetase in chorionic villi. The diagnosis was confirmed after amniocentesis by normal argininosuccinate synthetase activity in the cultured amniotic fluid cells and by a normal citrulline concentration in the amniotic fluid. The prediction of a normal fetus was confirmed at term by the birth of a non-citrullinaemic boy.
OBJECTIVE: To investigate the feasibility of various molecular forms of hemoglobin as markers for fetal nucleated red blood cells (NRBCs). METHODS: The presence of epsilon and gamma globin positive NRBCs was investigated in pure fetal blood and in blood from pregnant women before and after chorion biopsy. Maternal samples were enriched for NRBCs by various conventional methods, including limited enrichment by only positive CD71 selection or single density gradient. We searched for fetal cells on slides by automated scanning. Fetal cells were defined by (1) the presence of epsilon or gamma globin and (2) simultaneously by the presence of a Y chromosome signal. RESULTS: 18 of 25 gamma globin positive cells identified in blood samples after chorion biopsy were chromosome Y signal positive, and 1 cell had two X chromosome signals. 263 of 339 epsilon globin positive cells identified in blood samples after chorion biopsy were hybridized with X and Y chromosome probes. None had two X signals, and 249 were Y positive. In blood samples before chorion biopsy, only 1 epsilon globin positive fetal NRBC and no epsilon globin positive maternal NRBCs were found. CONCLUSIONS: Epsilon globin may be specific for fetal NRBCs. Only 1 epsilon globin positive fetal cell was identified in 1 of 12 blood samples before chorion biopsy, representing a total of 182 ml of maternal blood. This suggests that most fetal cells found in maternal blood by fluorescence in situ hybridization methods may not be NRBCs.
We assessed the effect of maternal cell contamination on the sensitivity of prenatal diagnosis by fluorescence in situ hybridization (FISH) on overnight attached mesenchymal chorionic villus cells. Double targets FISHs with X and Y chromosome-specific probes were performed on parallel samples from the same pregnancies: (1) samples of assumed fetal tissue retained during dissection, and (2) samples of suspected maternal tissue discarded during dissection. In the karyotypically male samples the tissue retained during dissection contained 0-3% nuclei with two X-specific signals each. In the tissue discarded from the karyotypically male samples 0-50% of the nuclei had two X-specific signals each. We conclude that given thorough dissection of chorionic villi, the sensitivity of prenatal diagnosis of aneuploidies by FISH on overnight attached samples of this tissue is not critically affected by maternal cell contamination.
BACKGROUND: Therapeutic benefits of nonsteroidal anti-inflammatory drugs (NSAIDs) are offset by their gastrointestinal side effects. We evaluated whether oral ketotifen, which prevents experimental NSAID-induced gastric mucosal injury, is superior to placebo in preventing NSAID-induced gastropathy. DESIGN: Prospective, randomized, double-blind, placebo-controlled clinical trial. SETTING: Rheumatology clinic in a tertiary care hospital. PARTICIPANTS: A majority of the 53 subjects had rheumatoid arthritis (n = 36) or osteoarthritis (12). Those with comorbidity, gastrointestinal (GI) symptoms or abnormal endoscopic findings at entry were excluded. Persons on steroids or NSAIDs in the previous month were also excluded. The subjects were started on indomethacin 25 mg thrice daily. INTERVENTION: Subjects were randomly allocated to receive 2 mg ketotifen or placebo tablets. Compliance was measured by tablet count. OUTCOME MEASURE: At the end of every week a questionnaire was administered to elicit GI symptoms or adverse effects. Every patient underwent endoscopy after four weeks. RESULTS: Of 53 patients recruited (27 drug, 26 placebo), three (2 drug, 1 placebo) dropped out. The age, sex, NSAID use and clinical conditions were similar in the two groups. Eight in the drug group and 16 in the placebo group developed GI symptoms and/or endoscopic lesions (relative risk 0.51, 95% CI 0.27-0.95). The difference was significant on intention-to-treat analysis. CONCLUSIONS: Ketotifen significantly reduced the risk of GI side effects in patients on indomethacin.