Successful triplet pregnancy in a patient with a unicornuate uterus with a cavitary communicating rudimentary horn

In a patient with primary infertility, ovulation was inducedby monitored stimulation with human menopausal gonadotrophins(HMG) because of polycystic ovarian disease. Infertility work-uphad shown a unicornuate uterus with a cavitary communicatingrudimentary horn. The husband showed a varicocele-related moderateoligoasthenoterato-zoospermia. A triplet pregnancy occurredin a third HMG ovulation induction cycle combined with intra-uterineinsemination of the husband's washed semen. The pregnancy wascarefully monitored, and measures to prevent premature deliverywere taken. Because of the patient's obvious discomfort in thepresence of premature labour, Caesarean section was performedat 33 weeks gestation and three healthy infants were delivered.This is the first report of a successful triplet pregnancy ina women with a unicornuate uterus. The reproductive and obstetricoutcome of this condition in general, and in the case of multiplepregnancy, is discussed.     

Limb-body wall complex: 4 new cases illustrating the importance of examining placenta and umbilical cord

Limb-body wall complex (LBWC) is a rare, sporadic, congenital defect defined as a combination of at least two of three characteristics: 1. limb defects, 2. anterior body wall defects, and 3. exencephaly or encephalocoele with/without facial clefts. Three pathogenic mechanisms have been proposed: early amnion rupture, vascular disruption and embryonic dysgenesis. In this study we carried out the pathological evaluation of four fetuses with LBWC and their placentas. None of the cases had craniofacial defects. Three fetuses showed an abdominal wall defect with eventration of abdominal organs, cloacal exstrophy, absent external genitalia, abnormal internal genitalia, scoliosis and lower limb defects. One fetus showed failure of closure of both thoracic and abdominal walls with ectopia cordis, evisceration of left lung and abdominal organs, severe reduction defect of left arm, but normal colon, anus, bladder, genitalia and lower limbs. All cases had a short, malformed umbilical cord, incompletely covered by amnion. The umbilical vessels were embedded in an amniotic sheet which connected the skin margin of the anterior body wall defect to the placenta. These anomalies suggest an abnormal body stalk development as a pathogenic mechanism for LBWC. Prenatally, the abnormal fetoplacental attachment can be detected ultrasonographically by the end of the first gestational trimester. Postnatally, the examination of placenta, umbilical cord and membranes is crucial in confirming the diagnosis of LBWC.     

Monochorionic and dichorionic twin pregnancies discordant for fetal anencephaly: a systematic review of prenatal management options

The aim of this study was to evaluate the effect of selective feticide (SF) compared to expectant management (EM) on perinatal outcome in dichorionic and monochorionic twins discordant for anencephaly. For this purpose, we conducted a systematic review of literature and added ten unpublished cases. As a result, we found that in dichorionic twins, mean gestational age (GA) at birth in the SF group was 38.0 weeks versus 34.9 weeks (P = 0.0002). Mean birth weight was 2922 g in the SF group versus 2474 g (P = 0.03). In monochorionic twins, mean GA at birth was 35.2 weeks versus 32.7 weeks (P = 0.1). Mean birth weight was 2711 g versus 1667 g (P = 0.0001).We conclude that while SF does not reduce perinatal mortality, it does result in significantly longer gestations and higher birth weight, and appears to be the management of choice in dichorionic twins discordant for anencephaly. In monochorionic twins, SF also increases birth weight, but in view of the complexity of this group, no clear recommendations can be made.     

Effects of intensity of repetitive acoustic stimuli on neural adaptation in the ventral cochlear nucleus of the rat

To study neural adaptation as a function of stimulus intensity, auditory near-field evoked potentials were recorded from the ventral cochlear nucleus in awake Long Evans rats. Responses to 250-ms trains of repetitive clicks (pulse rates ranging from 100 to 1000 pulses per second) were collected at stimulus intensities of 5, 10, 30, 50 and 70 dB SPL. The amplitude of the first negative (N₁) component of the average evoked potentials to individual pulses in the train was measured by using a subtraction method. The N₁ responses were normalized with respect to the highest cochlear nucleus potential observed in the train, and then plotted as a function of click position in the train. As expected, the general trend of the curves was an exponential decay reaching a plateau more or less rapidly as a function of both intensity and rate of stimulation. Fitting these curves with exponential decay equations revealed that the rapid time constant decreased for increasing stimulus intensities whereas the short-term time constant is relatively independent of intensity. The amount of adaptation (expressed as the ratio of the plateau to the first peak amplitude) was substantially less prominent at low intensities (5–10 dB SPL) and low rates (100–200 pulses per second) than at higher intensities and high rates. These results indicate that adaptation patterns obtained in the ventral cochlear nucleus by using near-field evoked potentials exhibit properties comparable to those already present at the level of the auditory nerve.     

Combined effects of noise and styrene exposure on hearing function in the rat

Combined exposure to both noise and aromatic solvents such as styrene is common in many industries. In order to study the combined effects of simultaneous exposure to both noise and styrene on hearing, male adult Long-Evans rats were exposed either to 750 ppm styrene alone, to a 97 dB SPL octave band of noise centered at 8 kHz, or to a combination of noise and styrene. The exposure duration was 6 h/day, 5 days/week, for 4 consecutive weeks. Auditory function was tested over a frequency range from 2 to 32 kHz by recording near field potentials from the inferior colliculus, whereas histopathological analyses of the cochleae were performed with conventional morphometric approaches. Whereas both noise and styrene each caused permanent threshold shifts, the mechanisms of cochlear damage were different. Noise-induced hearing loss was mainly related to injuries of the stereocilia, whereas styrene-induced hearing loss was related to outer hair cell losses. Following the combined exposure, the threshold elevations as well as the cell losses exceeded the summed loss caused by noise and by styrene alone in the range of 8-16 kHz. Therefore, these results suggest that the two ototoxicants can cause a permanent synergistic loss of auditory sensitivity.     

Influence of raising maternal blood pressure with angiotensin II on utero-placental and feto-placental blood velocity indices in the human

1. The effect of doubling doses of angiotensin II on maternal systemic blood pressure and arcuate and fetal umbilical artery Doppler velocity profiles has been investigated in 10 women in first- and 10 in second-trimester pregnancy. Ten non-pregnant women were also studied. 2. A progressive decrease in the pressor response to angiotensin II in early pregnancy as previously described was confirmed. 3. Angiotensin II induced a significant dose-dependent increase in the pulsatility index (a measure of downstream resistance) in the umbilical artery in both first- and second-trimester patients. There was an apparent increase in the threshold response of the pulsatility index to angiotensin II in the umbilical artery as pregnancy progressed. There was also a significant correlation between changes in maternal systolic or diastolic pressure and change in umbilical artery pulsatility index, but this did not differ between the two trimesters. This suggests that the increase in pulsatility index is related to blood pressure rather than angiotensin II. This is consistent with reports that angiotensin II does not cross the haemomonochorial placenta. 4. Basal pulsatility index in the arcuate artery fell with increasing gestation. There was a significant inverse association between the evoked change in maternal systemic blood pressure and the change in arcuate artery pulsatility index, suggesting local vasodilatation. 5. We conclude that acutely increasing maternal blood pressure leads to increased vascular resistance on the fetal side of the circulation.     

The influence of angiotensin II-induced vasoconstriction on common carotid artery blood flow and velocity-time profiles in normal women.

Non-invasive methods of measuring blood velocity, especially Doppler velocimetry, are being increasingly used in obstetrics to provide observational information. We report a preliminary study of their usefulness in experimental studies. Doppler velocimetry was used to assess blood flow and velocity-time profiles in the common carotid artery of seven women of reproductive age before and during the incremental administration of angiotensin II. Angiotensin II infusion evoked the expected increments in systolic and diastolic arterial pressure and fall in heart rate. Angiotensin II was associated with a dose-dependent fall in maximum blood velocity, which, at an average rise in systolic blood pressure of 23 mmHg, had fallen from 91 +/- 16 to 52 +/- 4 (mean +/- SD, p < 0.01). Absolute maximum blood velocity was strongly correlated with systolic and diastolic blood pressures (p < 0.001 for both). The minimum velocity was unaltered throughout, and the calculated flow did not change significantly (490 +/- 100 cf. 380 +/- 50 ml/min). Overall, these findings are in agreement with those previously reported using invasive methods of monitoring flow during angiotensin II infusion, and further support the usefulness of Doppler velocimetry as an investigative tool in human physiology and pharmacology.However, the pulsatility index, resistance index and systolic/diastolic velocity ratio all fell significantly during angiotensin II infusion (p < 0.01 for all). The conventional interpretation of a fall in these indices, i.e. reduced downstream resistance, is clearly erroneous under these circumstances, since angiotensin II induces arteriolar vasoconstriction. This illustrates the importance of interpretation of Doppler velocity envelopes in the light of pharmacological mechanisms likely to be evoked by the experimental procedure.     

Differentiated genotoxic response of carcinogenic and non-carcinogenic benzacridines and metabolites in rat hepatoma cells

Two closely related hepatoma cell lines were examined for theirgenotoxic response to benzacridines and their metabolites bythe appearance of alkaline labile DNA sites: H₅, a dedifferentiatedline expressing cytochrome P-448-dependent mono-oxygenase(s);and HF_1–4, a differentiated line expressing cytochromeP-450-dependent monooxygenase(s). The parent heterocycles hadno effect on both cell lines. In contrast to the 3, 4-dihydrodiolof benz[c]acridine the 3, 4-dihydrodiol of benz[a]acridine inducedno DNA strand breaks in both cell lines. All diol epoxides,however, induced DNA-damage in both cell lines, the syn derivativesin the same order of magnitude as the dihydrodiol of benz[c]acridine.The antidiol epoxides (epoxide group on the opposite side tothe benzylic hydroxyl group) were the most potent to induceDNA-single strand breaks. The diol epoxide of benz[c]acridinewas three times more efficient in HF_1–4 than in H5, whereasfor the diol epoxide of benz[a]acridine, the reverse was true.The results indicate that benz[c]acridine-3, 4-diol is oxidizedto metabolites which can induce DNA-damage. This is consistentwith the hypothesis that the benz[a]acridine and derivativesare not easily metabolized to active mutagens but more likelyare converted to inactive metabolites, possibly via N-oxidation.This is illustrated with 3, 4-diol-1-2 anti-diol epoxide ofbenz[a]acridine which is inactivated in cell line HF_1–4due to the reactivity of the epoxide ring in the bay region.Since all diol epoxides show similar activity in both hepatomacell lines, they are of great interest because of their abilityto detect DNA-damaging agents and to analyse their metabolicactivation and mechanism of action.