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Biomedical subjects

D Quick

Publications and source records attributed to D Quick.

7 recordsLinked to original sources

Light-chain paraproteins with lupus anticoagulant activity.

A patient with newly diagnosed multiple myeloma manifested by urine kappa light-chain excretion and a small monoclonal spike (0.4 g/dl), presented with lower extremity deep venous thrombosis. A preheparin plasma-activated partial thromboplastin time (aPTT) was prolonged at 68 sec (normal control 26-42 sec). Additional studies confirmed the presence of lupus anticoagulant activity in the serum: the modified Russell Viper Venom Time (MRVVT) was 73 sec (normal control 24-42 sec) and with a 50:50 mix of the patient's plasma and pooled normal plasma, the MRVVT remained prolonged. Kappa light chains (LC) were isolated from the patient's urine and their purity confirmed by electrophoresis and immunofixation using specific immunoglobulin antisera. The patient's LC mixed with pooled normal plasma demonstrated LA activity by in vitro clotting tests (plasma-activated partial thromboplastin time 62 sec, with normal control of 45 sec), MRVVT of 44 sec with normal control of 35 sec. Purified urinary kappa light chains from a control patient with multiple myeloma and normal clotting studies, failed to prolong either the plasma-activated partial thromboplastin time or the MRVVT. We hypothesize that kappa LC in our patient demonstrated LA activity, which was unique to these LCs. Paraproteins with LA activity, to date, have included only intact immunoglobulins (Ig). While intact Ig paraproteins have been reported to possess LA activity, this is the first report to our knowledge of light-chain paraproteins possessing similar activity and resulting in clinically evident thrombosis. Light chain paraproteins could serve as useful models for further study of the mechanisms of activity of acquired LA inhibitors.

Aged↗

Placental transfer of fentanyl in early human pregnancy and its detection in fetal brain.

We have investigated the transfer of fentanyl across the early human placenta in 38 women (8-14 weeks' gestation) undergoing termination of pregnancy. After administration of a bolus dose of fentanyl 2 micrograms kg-1 at induction of anaesthesia, maternal blood n = 38), placenta (n = 38), amniotic fluid (n = 38) and fetal brain (n = 7) samples were collected and assayed for fentanyl by radioimmunoassay. Fentanyl was detected in all placental and fetal brain samples but not in amniotic fluid. There was a rapid decrease in fentanyl concentrations in maternal serum after the bolus but placental concentrations had not started to decline 30 min later. There was no difference in placental drug concentrations at different gestational ages. These data suggest that there is rapid transfer of fentanyl to the fetus in early pregnancy and that the drug remains in fetal tissue for some time after the initial dose is given to the mother.

Abortion, Therapeutic↗

In-vivo measurement of intrauterine gases and acid-base values early in human pregnancy.

A new multiparameter sensor that combines electrochemical and fibre-optic technology was used for continuous in-vivo investigation of pH, carbon dioxide partial pressure (PCO(2)), oxygen partial pressure (PO(2)), bicarbonate concentration (HCO(3)(-)), base excess, and oxygen saturation (O(2)Sat) early in human pregnancy. The sensor was inserted into the amniotic cavity and the placental bed of 16 pregnancies at 10-15 weeks gestation, before termination under general anaesthesia. Amniotic fluid and retroplacental blood from the same site were also aspirated and analysed by means of cartridges and a portable blood gas analyser. Eleven series of measurements were obtained. The variation in measurements over the 5 min of monitoring was </=10% for all parameters. The sensor was damaged during insertion into the amniotic cavity in one case and in the placental bed in four cases. Measurements of PO(2) in both the amniotic cavity and the placental bed and of pH in the placental bed were higher using the cartridges than in vivo. The results indicated that in-vivo monitoring of fetoplacental gas and acid-base with a sensor is stable and accurate. Such technology will be helpful in improving our understanding of the fetoplacental metabolism in normal and complicated pregnancies.

Acid-Base Equilibrium↗

Acute mitral valve regurgitation created in sheep using echocardiographic guidance.

BACKGROUND AND AIM OF STUDY: This study was designed to determine: (i) Whether acute mitral valve regurgitation (MVR) due to chordal rupture can be reproducibly created under echocardiographic guidance; (ii) what degree of MVR can be created; (iii) what degree of acute regurgitation is survivable; and (iv) whether acute MVR due to chordal rupture progresses over time. METHODS: In a pilot group of six juvenile farm-bred sheep, selected chordae tendineae were ruptured using either a biopsy needle or endoscopic scissors under echocardiographic guidance, without need for cardiopulmonary bypass. Sheep were sacrificed acutely (n = 2), and at six weeks (n = 2) or eight weeks (n = 2). When the technique was optimized, five sheep entered a study group in which chords were ruptured using endoscopic scissors; the sheep were sacrificed 16 weeks after surgery. RESULTS: In the pilot study, acute MVR (grade 2-4+) was produced in all sheep, normal ventricular wall motion was maintained, with minimal progression of regurgitation over time. In one pilot sheep which did not survive, grade 4+ MVR was created acutely. Use of endoscopic scissors was preferable to the biopsy needle. In the study group, acute MVR (grade 2-4+) was produced in all five sheep, and was still present at 16 weeks, with progression in only one animal. CONCLUSIONS: This pilot study demonstrated that controlled degrees of survivable acute MVR due to chordal rupture can be created under echocardiographic guidance, with minimal progression of MVR over time. This animal model can be applied to investigate the pathogenesis of clinical MVR, and to suggest appropriate medical or surgical intervention.

Acute Disease↗

Cloning and sequence analysis of the human acidic fibroblast growth factor gene and its preservation in leukemia patients.

Acidic fibroblast growth factor (aFGF), also known as heparin-binding growth factor 1, is a mitogen for a variety of mesoderm- and neuroectoderm-derived cells. Several different aFGF mRNA species resulting from alternative splicing have been reported. These results suggest that the gene structure and regulatory mechanism for gene expression of aFGF are complex. As a first step toward understanding aFGF gene structure, we have isolated nine overlapping genomic DNA clones spanning 54 kbp and determined the complete DNA sequences of all three coding exons. Comparison of the nucleotide sequences between the human and bovine DNA showed that the sequence similarity extended 2400 bp downstream from the coding region. Cloning of the aFGF gene allowed us to characterize this locus in acute nonlymphocytic leukemia (ANLL) patients. A fraction of ANLL patients (10-20%) have a deletion in the long arm of chromosome 5, whose distal breakpoint overlaps the aFGF locus. Therefore, a prospective cohort of eight ANLL patients was screened using three different repetitive sequence-free probes derived from the aFGF locus. Using beta-globin gene as a normalization probe for hybridizing band intensities, we conclude that there is no allelic loss or gross rearrangement within the 40 kbp stretch of the aFGF gene locus in ANLL patients with or without 5q- deletion. Consistent with this observation, the aFGF mRNA was not detected in the mononuclear cells derived from either an ANLL patient or a normal individual as judged by the reverse transcription and polymerase chain reaction. We also identified a DNA fragment, 10.7 kbp upstream from the first coding exon of human aFGF, whose sequence is conserved in both the primate and rodent genomes. Further characterization of this fragment is likely to provide insight into the significance of this high degree of conservation.

Amino Acid Sequence↗