Biomedical subjects
Publications and source records attributed to S L Tan.
The availability of miniaturized portable infusion devices has enabled the development of another important method of inducing ovulation in women with clomiphene-resistant anovulatory infertility (Labrie et al, 1984; Mason et al, 1984; Armar et al, 1986a). When cases are carefully selected and accurate ultrasound monitoring is used, very impressive conception rates are achieved (Armar et al, 1986a). The treatment is simple, effective and safe.
Pulsed electron paramagnetic resonance spectroscopy has been used to detect Mn(II)-ligand superhyperfine couplings in complexes with creatine kinase and in the Mn(II) metalloprotein concanavalin A. Electron spin-echo envelopes from Mn(II), bound in these complexes, are modulated by superhyperfine interactions between Mn(II) and nearby, weakly coupled nuclear spins. The characteristic frequencies of the modulations were obtained by Fourier transformation of the three-pulse, spin-echo envelopes. In transition-state analogue complexes of creatine kinase (enzyme-MnIIADP-anion-creatine), superhyperfine interactions from the directly coordinated nitrogen of the thiocyanate ligand give envelope modulations. The source of the modulations was confirmed by measurements with the 14N and 15N forms of thiocyanate. On the other hand, the nitrogen of coordinated nitrate, which is two bonds removed from the paramagnetic center, does not produce detectable modulations. In spectra for Mn(II) concanavalin A, envelope modulations are detected due to the nitrogen of the coordinated histidine residue. Complexes prepared in 2H2O give strong signals due to weakly coupled 2H. For Mn(II)-doped single crystals of sodium pyrophosphate, signals are observed in the frequency domain spectra that are due to coupling from 31P. Phosphorus signals from the ADP ligand in complexes with creatine kinase show approximately the same coupling constant but have a much broader line width.
During the deamination of S-2-aminopropanol by the AdoCbl-dependent ethanolamine ammonia-lyase of Clostridia sp., a catalytic intermediate accumulates whose active site contains two paramagnetic species: cob(II)alamin and a free radical derived from the substrate molecule. Spin-echo spectroscopy has revealed that the unpaired electron on the substrate-derived radical is delocalized over a nitrogen atom that from its quadrupole splittings is probably a component of a secondary amide group. Experiments with 15N- and deuterium-labeled propanolamine gave no evidence of an interaction between this unpaired electron and the nitrogen originally attached to the substrate molecule. These results strongly suggest that the substrate-derived radical in this intermediate has already lost its nitrogen, and that this radical is stabilized by delocalization of the unpaired electron onto a nitrogen most likely situated in one of the peptide bonds of the enzyme backbone.
A 29-year-old woman is described who presented with amenorrhea and galactorrhea with a large prolactinoma which regressed on bromocriptine therapy. Treatment with bromocriptine was stopped when pregnancy was diagnosed but 6 weeks later the prolactinoma had regrown with suprasellar extension and lateral invasion of the cavernous sinus. When treatment with bromocriptine was reinstituted symptoms subsided within 24 h and serum prolactin concentrations fell from 54,000 mM/l to 2800 mU/l within 5 days and 500 mU/l 2 days after that. Pregnancy proceeded without complications and she entered spontaneous labor at term and delivered a healthy baby. One year after delivery, on treatment with bromocriptine, her serum prolactin concentration remains within the normal range and the CT scan shows persistence of a small prolactinoma, confined to the pituitary fossa. Bromocriptine should be the primary treatment for prolactinomas regardless of tumor size and may be safely stopped when pregnancy is desired. If pituitary tumor complications occur during pregnancy, reintroduction of treatment with bromocriptine should again be the treatment of choice.
Premature ovarian failure accounts for 10% of cases of secondary amenorrhea, and in most cases its cause remains unknown. One mechanism by which it occurs is autoimmune destruction. A 21-year-old patient is described in whom autoimmune ovarian failure occurred in association with Addison's disease and primary hypothyroidism. Although premature ovarian failure is generally considered irreversible, the patient subsequently resumed spontaneous ovarian follicular activity.
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The effect of breast stimulation on cervical ripening was studied. One hundred patients who had completed 38 weeks' gestation and had uncomplicated antenatal courses were recruited and divided into two groups: treatment and control. In the treatment group, gentle breast stimulation of alternate breasts was performed first for 1.5 hours under monitoring in the hospital and then for three hours daily for three days at home. No uterine hypertonus was detected. It was found that there was a significant change in the Bishop score of 3.96 +/- 1.34 points in the stimulated group as compared with the control group 1.04 +/- 1.03 points. After three days, a cross-over trial was performed with the extreatment group becoming the control and the excontrol group undergoing breast stimulation for the same period of time and under the same conditions. Again, the excontrol group was found to have a better mean cervical score (3.11 +/- 1.42 points) than the extreatment group (0.76 +/- 0.97 points) during breast stimulation. It is stressed that no uterine hypertonus was detected with gentle, unilateral breast stimulation, and there were no maternal or fetal complications as a result of this modality of cervical ripening.
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Using resonance Raman and infrared absorption spectroscopies, we show that there are no energetically significant structural changes at the heme upon the quaternary structure transition in six-coordinate hemoglobins. These observations are at variance with the presently accepted mechanism for cooperativity, which postulates severe strain in the T quaternary structure of liganded hemoglobin. By consideration of the present results, and studies on deoxyhemoglobins and photodissociated hemoglobins, a view of the distribution of the free energy of cooperativity emerges. In five-coordinate deoxyhemoglobins the iron-histidine bond is able to respond to the protein structure, thereby accounting for a wide variation (40 cm(1] in its frequency. In contrast, when a sixth ligand is present and the iron is pulled into plane, the histidine-heme-ligand complex becomes structurally rigid, thereby preventing protein-induced changes at the heme. Instead, in liganded hemoglobin the changes in structure that occur at the subunit interface upon the quaternary structure transition are accommodated away from the heme by relatively weak bonds in the protein.
Nine of 10 adults, previously healthy patients who suffered cardiac arrest during or after anesthesia, recovered nearly complete neurological function when given iv phenytoin, 7 mg/kg. Phenytoin was given only after spontaneous heart beat and systolic blood pressure greater than 100 mm Hg had been restored and the diagnosis of neurological deficit had been established on the basis of unconsciousness, dilated and areflexic pupils as well as rigid and /or decerebrated posture. One patient recovered only partially, and eventually succumbed to other complications.
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Atrioventricular (AV) conduction, ventriculoatrial (VA) conduction, and the mechanism of tachycardia, were studied by programmed electrical stimulation before and after the administration of verapamil, in 10 patients with paroxysmal re-entrant supraventricular tachycardia. In 7 patients the tachycardia circuit was confined to the AV node. In 3 patients an accessory pathway conducting only in the ventriculoatrial direction was used during tachycardia. When administered intravenously during tachycardia, verapamil terminated the arrhythmia in 9 patients. Verapamil lengthened the effective and the functional refractory period of the AV node and the AV nodal transmission time in all patients in whom this could be studied. As a result of these changes, it was not possible to initiate tachycardia in 3 patients. The width of the zone of atrial premature beats able to initiate tachycardia (the tachycardia zone) narrowed in 5 patients, and increased in 2 patients. In 6 of these 7 patients the tachycardia zone shifted to longer premature beat intervals. Verapamil resulted in slowing of the heart rate during tachycardia. Apart from slowing in heart rate during tachycardia and termination of tachycardia after intravenous verapamil, the 3 patients with an accessory pathway showed no beneficial effect of verapamil on the mechanism of initiation of tachycardia. Five patients were restudied after 2 to 3 weeks of oral administration of verapamil. Though less, effects were similar to those obtained after intravenous administration.
The present experiments compared the maturational and developmental competence of immature oocytes derived from stimulated cycles, following culture in a newly designed in-vitro maturation medium (IVM-medium) or in standard tissue culture medium (TCM-199; control). The results indicated that maturation and fertilization rates were comparable when the cumulus-free M-I stage oocytes were matured in the IVM-medium (78.6%) or the control medium (70.8%). However, there was a significant difference in blastocyst development (P < 0.05) when M-I oocytes were matured in these two media (19.6 versus 7.7%). Both maturation and early embryonic development rates of GV-stage oocytes were significantly higher (P < 0.01) in the IVM-medium (maturation: 75.7%; blastocyst: 12.9%) compared with control (maturation 55.7%; blastocyst: 0.0%). Moreover, embryos developed to the blastocyst stage at a higher rate in both media if GV-stage oocytes had matured within 24 h compared with 48 h of culture. These results demonstrate that immature human oocytes derived from stimulated ovaries can achieve maturation and early embryonic development in vitro, especially in the new IVM-medium, which may allow additional embryos to be produced for clinical use at embryo transfer.
OBJECTIVE: To evaluate the changes in ovarian volume and the reproductive outcome after laparoscopic treatment of polycystic ovaries (PCOS) in clomiphene-resistant anovulatory women. DESIGN: A prospective study of women undergoing laparoscopic treatment of polycystic ovaries. Ultrasound examination for three-dimensional (3D) volume determination was performed before and after surgery. SETTING: University teaching hospital. PATIENTS: Thirty-four women with polycystic ovarian syndrome who failed to ovulate with clomiphene citrate and who subsequently underwent laparoscopic ovarian drilling. INTERVENTIONS: Laparoscopic ovarian drilling and three-dimensional ultrasound examination. MAIN OUTCOME MEASURES: Cumulative probability of conception and changes in ovarian volume. RESULTS: Ovulation rate after the procedure was 30/34 (88.2%). Using Life Table Analysis, the cumulative probability of conception at 12 months follow-up was 70% (median, 8.1 months). The preoperative ovarian volume was 12.2 +/- 1.8 cm3 and 1 week after surgery it was 13.6 +/- 1.5 cm3. The ovarian volume 3 weeks after surgery, 6.9 +/- 1.3 cm3, was significantly smaller than that before surgery. CONCLUSIONS: Laparoscopic treatment of polycystic ovaries in women with clomiphene-resistant PCOS is associated with an ovulation rate of 88.2% and a cumulative pregnancy rate of 70% at 12 months. It appears also that laparoscopic ovarian drilling may result in a transient increase, with a subsequent significant reduction, in ovarian volume.