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Biomedical subjects

R S Kuhlmann

Publications and source records attributed to R S Kuhlmann.

15 recordsLinked to original sources

Maternal metabolic abnormalities in twin-to-twin transfusion syndrome at mid-pregnancy.

We report abnormal maternal laboratory parameters in twin-to-twin transfusion syndrome (TTTS) at mid-pregnancy. A retrospective chart review was undertaken of 109 patients with TTTS evaluated for placental laser surgery. Complete blood count (CBC), blood type and Rh factor, urine analysis and serum chemistry panel were obtained preoperatively, with the CBC and serum albumin repeated on the first postoperative day. The mean gestational age was 21.2+/-1.7 weeks. Initial abnormal values included hematocrit (32.1+/-3.0%), hemoglobin (11.0+/-1.03 g/dl), serum magnesium (1.71+/-0.17 mg/dl), total protein (6.08+/-0.55 g/dl) and albumin (3.06+/-0.34 g/dl). Despite minimal blood loss and conservative fluid replacement mean hematocrit, hemoglobin, and albumin were 27.3+/-2.74%, 9.3+/-0.94 g/dl and 2.56+/-0.23 g/dl, respectively on postoperative day one. Weight gain (8.0+/-5.5 lb.) and low urinary output were characteristic peri-operative events. Maternal hypoproteinemia and anemia occur in TTTS at mid-pregnancy. This may contribute independently to amniotic fluid production rates in the fetuses, and explain in part the maternal sensitivity to intravenous fluids in multiple pregnancy.

Adolescent↗

Treating previable twin-twin transfusion syndrome with fetoscopic laser surgery: outcomes following the learning curve.

AIMS: We have performed fetoscopic laser occlusion of chorioangiopagous vessels (FLOC) in previable pregnancies affected by twin-twin transfusion syndrome (TTTS) since 1988. Treatment outcomes obtained after the procedure's learning curve are presented and compared to those from other centers performing FLOC or other treatment methods. METHODS: A total of 100 cases of FLOC have been performed at our centers. The later 67 TTTS patients had a mean gestational age of 21.1 +/- 1.7 weeks (range 18-24.5) with a mean fundal height of 33.1 +/- 4.9 cm (range 27-44) when treated. Eighteen (27%) had failed another treatment method before FLOC. RESULTS: All 67 cases have delivered with 82% (55/67) having at least one surviving twin and 93/134 (69%) of the twins surviving overall. Thirty-eight have surviving twins, 17 have one survivor (5 neonatal and 12 fetal deaths), and 12 have none. The mean duration of pregnancy following FLOC was 9.9 +/- 5.5 weeks (range 1.0-19). Only 4 of 93 (4.3%) survivors have significant handicaps at a mean follow-up of 14.3 +/- 10.1 months (range 1.0-34). CONCLUSION: Fetoscopic laser occlusion of chorioangiopagous vessels within the vascular equator limits the duration of fetal pathophysiology in TTTS and results in neonatal outcomes superior to the modified procedure and other treatment methods.

Diseases in Twins↗

Fetoscopic laser ablation of placental vessels in severe previable twin-twin transfusion syndrome.

OBJECTIVE: We undertook a pilot study to determine the feasibility and efficacy of fetoscopic laser occlusion of chorioangiopagous vessels in severe previable twin-twin transfusion syndrome. STUDY DESIGN: A total of 35 patients were referred to the investigators with ultrasonographic findings consistent with twin-twin transfusion syndrome, posterior placental implantation, gestational age < 25 weeks, and clinical hydramnios. Placental vessel occlusion was performed with a rigid 2.9 x 3.85 mm dual-channel fetoscope and neodymium:yttrium-aluminum-garnet laser light. RESULTS: Of the original 35 patients, 5 were eliminated preoperatively and 4 intraoperatively for various factors. The 26 treated patients had a mean gestational age of 20.8 weeks (range 18 to 24) and a mean fundal height of 36.1 cm (range 29 to 44). One patient has surviving triplets, 8 have surviving twins, 9 have a single survivor (2 neonatal and 7 fetal deaths occurred in this group), and 8 have no survivors (all had pregnancy loss within 3 weeks of treatment). The cases with survivors were delivered for obstetric indications at a mean of 32.2 weeks (range 26 to 37), having gained a mean of 11.7 weeks (range 6 to 17) in utero. Fifty-three percent (28/53) of the fetuses survived with 96% (27/28) developing normally at a mean age of 35.8 months (range 1 to 68). Thirty-three of 35 placentas were monochorionic with chorioangiopagous vessels on gross and microscopic evaluation. CONCLUSIONS: Fetoscopic laser occlusion of chorioangiopagous vessels is technically feasible and improves the course and outcome of severe twin-twin transfusion syndrome in previable fetuses.

Feasibility Studies↗

Cardiovascular teratogenicity of terbutaline and ritodrine in the chick embryo.

OBJECTIVE: We determined the teratogenic effects of terbutaline and ritodrine, both beta 2-sympathomimetic agonists, on the stage 24 (4-day) chick embryo. STUDY DESIGN: We used a topical method of application of terbutaline or ritodrine to the stage 24 chick embryo in ovo. Doses of terbutaline ranged from 5.5 x 10(-10) to 6.5 x 10(-9) mol per embryo, and ritodrine doses ranged from 4.6 x 10(-11) to 4.6 x 10(-8) mol per embryo. To further determine the pharmacologic nature of the teratogenic potential of terbutaline or ritodrine, the experiments were repeated after pretreatment with butoxamine hydrochloride, a preferential beta 2-antagonist, or metoprolol tartrate, a preferential beta 1-antagonist, 4 hours before application of terbutaline or ritodrine. RESULTS: Terbutaline treatment was associated with significantly higher rates of anomalies than in controls at all dosages used, whereas ritodrine induced significantly more anomalies at or above doses of 4.6 x 10(-9) mol per embryo. At an equimolar dose pretreatment with butoxamine hydrochloride significantly reduced the cardiovascular teratogenic effects of terbutaline and ritodrine. Pretreatment with metoprolol tartrate at any dose did not significantly reduce terbutaline's potential. Metoprolol, at doses tenfold or 100-fold higher than ritodrine, was able to significantly reduce the teratogenic effects of ritodrine. CONCLUSIONS: Our data suggest that terbutaline and ritodrine are teratogenic in the chick and that these agents exert their teratogenic effects primarily through stimulation of the beta 2-adrenergic receptor.

Animals↗

Placental histology in fetuses between 18 and 23 weeks' gestation with abnormal karyotype.

Placentas from karyotypically abnormal fetuses (18 to 23 weeks' gestation) were analyzed prospectively at the light microscopic level. Group I consisted of 14 control placentas. Group II consisted of 14 placentas from fetuses with an abnormal karyotype. Secondary and tertiary stem villi counts, small muscular artery counts, and total vessel counts were determined per 100 x field. There were no differences in secondary and tertiary stem villi counts between groups. A significant decrease in small muscular artery counts (p less than 0.01) and total vessel counts (p less than 0.01) was noted in group II. Placental and fetal weights were comparable between groups. This undervascularization may represent placental immaturity as a result of arrested or delayed angiopoiesis. It appears that this abnormality is established before the third trimester and may be enhanced by late vascular obliteration as reported by others. These data substantiate the concept that the structure and function of the placenta is determined to a great degree by fetal karyotype and may help explain the morbidity and mortality seen in these fetuses.

Chorionic Villi↗

Tissue and plasma levels of a teratogenic dose of dopamine in the chick embryo following pretreatment with metoprolol or phosphate buffered saline.

Metoprolol pretreatment has been shown to reduce the cardiovascular malformation rate produced by topical doses of dopamine in the stage 24 chick embryo. We report on the tissue and plasma levels and teratogenic effect of dopamine hydrochloride following topical application of a teratogenic dose in stage 24 chick embryos pretreated with either metoprolol tartrate or phosphate buffered saline (PBS). Pretreatment with either metoprolol or PBS resulted in similar patterns of dopamine distribution in the head, body, and heart, with peak levels occurring at 12 hours after dopamine treatment. Plasma concentrations of dopamine were similar for both PBS and metoprolol pretreated embryos, with plasma levels exceeding tissue concentrations, but also peaking at 12 hours after dopamine treatment. Pretreatment with PBS followed by a teratogenic dose of dopamine resulted in a decrease in the teratogenic effect of dopamine similar to that found in previous work in our lab with pretreatment with metoprolol. The developing chick cardiovascular system experiences peak susceptibility to the teratogenic effects of dopamine at stage 24 during development, which represents a time frame of about 12 hours. A delay in the peak levels of dopamine to 12 hours after dopamine treatment as compared to previous work in our lab reporting peak levels of dopamine at 1 hour, suggests that the previously reported antiteratogenic effects of metoprolol may be due, at least in part, to a delayed absorption of dopamine past the time of peak susceptibility of the embryo to the teratogen.

Animals↗

Ventricular blood pressure and cardiac output changes in epinephrine- and metoprolol-treated chick embryos.

The effects of a teratogenic dose (5 micrograms) of epinephrine on mean ventricular blood pressure (MVBP) and cardiac output (CO) at one and two hours after treating stage 24 chick embryos were investigated. Previous work demonstrated that a differential response in terms of cardiac rhythm during the first hour after epinephrine treatment was related to pathogenesis of two contrasting types of aortic arch malformations. Absence of one or more aortic arches occurred more frequently in embryos which developed a characteristic dysrhythmia, while persistence of the left fourth aortic arch (PL4AA) occurred more frequently in nondysrhythmic embryos. In this study, dysrhythmic epinephrine-treated embryos exhibited reductions in both MVBP and CO at one hour after treatment when compared to control values. Nondysrhythmic epinephrine-treated embryos exhibited elevated MVBP and no change in CO at one hour after treatment. MVBP and CO in recovered dysrhythmic and nondysrhythmic embryos were similar to control values at two hours following epinephrine treatment. MVBP and CO measurements were obtained from embryos which were pretreated with metoprolol and then subsequently treated with epinephrine. Metoprolol is a beta 1-adrenoreceptor antagonist which was previously shown to block the teratogenic effects of epinephrine and other catecholamines with beta 1-adrenoreceptor agonist properties. Pretreating embryos with metoprolol in this study reduced the dysrhythmogenic potential of epinephrine and also blocked the MVBP and CO changes observed in embryos treated with epinephrine alone. We conclude that pathogenesis of 1) abnormally absent aortic arches is related to dysrhythmogenesis, reduced MVBP, and reduced CO, and 2) an abnormally persistent left fourth aortic arch is related to elevated MVBP in the epinephrine model.

Animals↗

Fetal sacrococcygeal teratoma.

Early prenatal diagnosis of fetal sacrococcygeal teratoma (SCT) has enabled the perinatal team to institute management of this condition during the perinatal period. We report 2 additional cases to our previous 27 cases including 1 which represents the earliest diagnosis of SCT. Fetal SCT behaves in a different manner than neonatal SCT. In utero manipulation of fetal SCT may be possible if diagnosis is made during the second trimester.

Adult↗

The spontaneous occurrence of aortic arch and cardiac malformations in the white Leghorn chick embryo (Gallus domesticus).

Spontaneous aortic arch and cardiac malformations occur in White Leghorn chick embryos at a relatively high rate. Although this breed of Gallus domesticus is widely used for biomedical and biological research, no previous study has recorded the incidence of these defects. We found aortic arch malformations in 7.1% (14 of 196) and ventricular septal defects in 11.7% (23 of 196) of living embryos. Defects occurred alone or as a combined pattern. Our findings suggest that the cardiovascular defects in the chick embryo documented in past studies may, in some cases, have been part of normal spontaneous occurrence, rather than the major result of experimental manipulation.

Animals↗

The role of dysrhythmic heart function during cardiovascular teratogenesis in epinephrine-treated chick embryos.

Chick embryos were treated with a teratogenic dose (5 micrograms) of epinephrine hydrochloride at 4 days of development (stage 24). Heart rates were determined at 20, 40, and 60 minutes after treatment. The mean heart rate values for epinephrine-treated embryos were significantly less than values obtained for untreated and saline-treated control embryos. The decrements in mean heart rate could be explained by severe cardiac dysrhythmias that occurred in approximately 40% of epinephrine-treated embryos. The remaining 60% of embryos exhibited heartbeat patterns similar to controls. This finding enabled us to separate epinephrine-treated embryos into two physiologically distinct groups: dysrhythmia-positive and dysrhythmia-negative. Dysrhythmias were characterized by periods of bradycardia alternating with periods of asystole and were confirmed by electrocardiography. EKG data suggest that epinephrine induces cardiac conduction disturbances in some chick embryos. An additional experiment was conducted to identify the frequencies at which abnormally obliterated aortic arches, abnormally persistent aortic arches, ventricular septal defects, and embryonic death occurred in dysrhythmia-positive and negative embryos. Abnormally obliterated vessels and embryonic death occurred with significantly greater frequencies in dysrhythmia-positive embryos. Abnormally persistent vessels and ventricular septal defects occurred with significantly greater frequencies in dysrhythmia-negative embryos. We conclude that the production of specific malformations and decreased probability for survival in epinephrine-treated embryos are related to dysrhythmogenesis and bradycardia.

Abnormalities, Drug-Induced↗

Reduction of catecholamine-induced cardiovascular malformations in the chick embryo with metoprolol.

It has been documented that activation of the beta 1-adrenergic receptor mechanism is directly related to cardiovascular malformations associated with the heart and great vessels of the embryonic chick. These adrenergic receptors are believed to be present and functional in the innervated and noninnervated embryonic heart at early stages of development. The present study examined the effects of four sympathomimetic cardioactive amines on chick cardiovascular morphogenesis at Hamburger and Hamilton stage 24. Special attention was directed toward understanding dopamine teratogenicity. In order of decreasing potency at the maximum teratogenic dose (dopamine greater than isoproterenol greater than epinephrine greater than norepinephrine) each drug was found capable of producing aortic arch anomalies of the third, fourth, and sixth aortic arches and ventricular septal defects (VSD). A new specific beta 1-adrenergic antagonist, metoprolol tartrate, was employed in an attempt to lower the incidence of these cardiovascular malformations. Pretreatment with this selective beta 1-blocker profoundly reduced the incidence of malformations within any amine-treated group. These experiments demonstrate that dopamine, as well as the other sympathomimetic amines, is a potent teratogen and most likely produces these cardiovascular malformations by primarily stimulating the beta 1-adrenoreceptor in the embryonic chick.

Abnormalities, Drug-Induced↗

Diamnionic monochorionic twin gestations: an overview.

Monochorionic (MC) twins account for about 20-30% of all twins, but contribute disproportionately to mortality, intrauterine growth restriction, and preterm delivery compared with dichorionic (DC) twins. This higher mortality in MC twins is likely due to the effects of placental morphologic characteristics, which include complex vascular communications between the twins associated with twin-twin transfusion syndrome (TTTS), and the tendency for the common placenta to be shared either symmetrically or asymmetrically. In assessment of clinical outcomes for TTTS, artery to vein anastomoses in the absence of artery to artery or vein to vein, especially if present with placental asymmetry, carry the worse prognosis. Chorion status in twins forms the basis for clinical risk assessment and can be determined by 7 menstrual weeks using transvaginal sonography. The variable results reported in the literature for intertwin umbilical artery Doppler findings in MC twins may be explained by differences between sonographic and clinical criteria (including differential hemoglobin concentrations) reported by various investigators. Antenatal fetal Doppler assessment of the umbilical artery and cerebral arteries can help distinguish between TTTS and placental insufficiency in MC twins. Significant restriction of fetal growth occurs in about 25% of multiple gestations, accounting for about 17% of all growth-retarded infants. Redistribution of fetal blood (brain-sparing effect), as determined by Doppler interrogation of fetal cerebral and umbilical arteries, occurs more commonly in MC twins compared to DC twins and in growth-restricted MC twins compared to nongrowth-restricted MC twins. Overall, the prognosis is poorer for the donor twins in TTTS and there is a greater prenatal death rate for the donor (18-35%), and a higher overall survival rate for recipients following fetoscopic laser treatment. Finally, the clinical and sonographic findings suggest that the polyhydramnios/oligohydramnios sequence seen in MC twins likely represents a spectrum strongly linked to placental variables.

Amnion↗