Novel application of hydrotropic solubilizing additives in the estimation of aspirin in tablets.

Highly concentrated aqueous solutions of various hydrotropic agents like sodium benzoate, sodium salicylate, sodium acetate, sodium citrate, nicotinamide and sodium ascorbate have been observed to enhance aqueous solubilities of a large number of poorly water-soluble drugs. In the present investigation hydrotropic solubilization technique has been employed to solubilize poorly water-soluble aspirin (analgesic and antipyretic drug) by 0.5 M ibuprofen sodium solution to carry out titrimetric analysis of aspirin in tablet dosage form. Results of analysis by proposed method and Phamacopoeial method are very comparable. Proposed method is new, rapid, simple, accurate, and reproducible. Statistical data proved the accuracy, reproducibility and the precision of proposed method.

[Persistent left-sided superior vena cava diagnosed after flow-directed pulmonary artery catheterization; report of a case].

We describe a case of persistent left-sided superior vena cava discovered after insertion of a pulmonary artery (PA) catheter. The diagnosis was suggested by chest X-ray after PA catheter placement and was subsequently confirmed by an echocardiograph. A 68-year-old man was admitted to our ICU because of septic shock induced by MRSA enterocolitis. In order to monitor the hemodynamic state of the patient, a PA catheter was inserted through the left subclavian vein after placement of a central venous and flexible double lumen catheters through the right internal jugular and subclavian veins, respectively. A chest X-ray showed the PA catheter passing along the left border of the heart. An echocardiograph showed the PA catheter passing through the coronary sinus into the pulmonary artery. Anesthesiologists and intensivists should be aware of the occurrence of left-sided superior vena cava in order not to mistake catheters placed in it as being in the arterial circulation or malpositioned outside of the venous circulation.

[Perioperative management of life-threatening intra-abdominal bleeding with intra-aortic balloon occlusion catheter].

Intra-thoracic aortic clamping using an intra-aortic balloon occlusion catheter (IABOC) is employed for patients with life-threatening intra-abdominal and/or extra-abdominal bleeding in spite of massive transfusion. For perioperative management, we inserted an IABOC preoperatively into a 59-year-old man with life-threatening intra-abdominal bleeding from an abscess formed around his traumatically injured pancreas. We could perform a safe operation in which bleeding was controlled by intermittently occluding the IABOC and the patient was thus prevented from developing into severe hemorrhagic shock. We experienced a usefulness of IABOC for a patient with life-threatening intra-abdominal bleeding uncontrolled due to intra-abdominal adhesion during the perioperative period. However, organ dysfunctions caused by ischemia and reperfusion following intra-aortic balloon occlusion must be prevented by shortening the occlusion time through use of an intermittent method such as described above.

Molecular cytogenetic studies in three patients with partial trisomy 2p, including CGH from paraffin-embedded tissue.

We report on three cases of partial trisomy 2p in which the identification and exact localization of the duplicated chromosome segment was possible only by application of molecular cytogenetic techniques. These included fluorescence in situ hybridization by use of wcp2, N-myc, and subtelomeric 2p probes and comparative genomic hybridization with DNA isolated from blood samples, frozen fetal tendon, and formalin fixed, paraffin-embedded fetal lung tissue. Two of the cases concerned fetuses of gestational week 20 and 24 with duplication of nonoverlapping terminal (2pter-->p24) and more proximal (2p25-->p23) segments and with distinctly different phenotypes. The third case was due to a de novo inverted duplication of 2p25-->p23, with loss of the subtelomeric region of 2p. This 53-month-old girl was a Bloom syndrome carrier. The patient had prenatal growth failure, borderline microcephaly, dilated lateral horns of the cerebral ventricles, transient cortical blindness, myopia, muscle hypotonia, and dilatation of the left renal collecting system. Dermal cysts were found on the glabella, the soles of both feet, and the vocal cord, causing respiratory embarrassment. Previously reported cases of pure trisomy 2p are reviewed, in an attempt to correlate clinical findings to overlapping regions in 2p. These cases illustrate the effectiveness of molecular cytogenetic methods in resolving subtle chromosomal aberrations in order to coordinate more accurately a chromosome regionspecific phenotype.

Use of interphase fluorescence in situ hybridization in third trimester fetuses with anomalies and growth retardation.

In the last few years, attention has been focused on the use of interphase fluorescence in situ hybridization (FISH) for prenatal diagnosis with chromosome-specific DNA probes in the second trimester. This technique is accurate, rapid, and detects the most common aneuploidies. We present a preliminary study using FISH technique on uncultured amniotic cells derived from 30 fetuses with ultrasonographic evidence of intrauterine growth retardation (IUGR) in the third trimester. Fifteen fetuses were males and 15 were females. Seven fetuses (23.3%) had abnormal chromosomal constitution: five (18.6%) had trisomy 21, one (2.35%) had trisomy 18, and one (2.35%) showed a mosaic trisomy 18. No abnormalities were detected in the other 23 fetuses. Amniocentesis combined with FISH appears to be a safe, rapid, and accurate alternative to blood sampling in the third trimester, reducing the clinical and emotional stress of the time required to complete chromosome analysis by routine cytogenetics.

Advanced FISH with directly labeled X, Y and 18 DNA probes as a tool for rapid prenatal diagnosis.

OBJECTIVE: To examine a rapid technique for identification and determination of fetal sex chromosomes and one autosome (chromosome 18) in uncultured amniotic fluids using fluorescence in situ hybridization (FISH) with directly labeled DNA probes and ignoring the use of proteinase K and Rnase. STUDY DESIGN: Twenty-five amniotic samples taken from pregnant women who were in their 18th gestational week and had advanced maternal age were studied for analysis of sex chromosomes and chromosome 18 with the FISH technique as well as standard cytogenetic analysis. RESULTS: Four hours after amniocentesis was performed, we identified the sex of the fetuses and disomy of chromosome 18 in a minimal sample of uncultured amniotic fluid by using directly labeled DNA probes for chromosomes X, Y and 18 (VYSIS) and ignoring the use of proteinase K and Rnase. CONCLUSION: The possibility of shortening the time required for identification of aneuploidies in a second-trimester fetus is useful in cases where fetal anomalies are ultrasonically diagnosed at a relatively advanced gestational age.

Heat stable and urea resistant alkaline phosphatase in maternal neutrophils from normal and Down syndrome pregnancies.

Activity levels of total and placental alkaline phosphatase (AP) were determined in maternal serum and neutrophils of normal and Down syndrome pregnancies. The placental iso-enzyme (PAP) was identified by its relative stability to urea and heat. Significant increase in the activity of all iso-enzymes across gestational stages was observed in maternal sera of 28 normal pregnancies. However, in the neutrophil extracts of the same blood samples no differences were detected between trimesters. Another set of experiments was aimed at finding diagnostic differences of PAP activity in maternal neutrophils of normal and trisomy 21 affected pregnancies. No differences of heat stable AP activity were found in maternal samples of 19 normal and 19 Down syndrome affected pregnancies. Urea resistant AP proportions were also similar when measured after 40 minutes of exposure (13 samples in each group). However, a marginally significant increase was observed in the mean value of the Down syndrome affected samples, after 60 minutes of urea treatment. In view of the above results we conclude that neutrophil AP activity is not as yet a useful marker for the screening of trisomy 21 fetuses.

Down's syndrome screening marker levels following assisted reproduction.

Maternal serum alpha-fetoprotein (AFP), human chorionic gonadotrophin (hCG), and unconjugated oestriol (uE3) levels were examined in 1632 women who had ovulation induction and 327 who had in vitro fertilization. There was a highly statistically significant increase in hCG and reduction in uE3 among those with ovulation induction. The median levels were respectively 1.09 and 0.92 multiples of the normal gestation-specific median (MOM) based on a total of 34582 women. Ovulation induction appeared to have no material effect on the median AFP level but this masked a significant increase when treatment was with Clomiphene (1.05 MOM) and a significant decrease when Pergonal was used (0.93 MOM). There was a highly statistically significant reduction in uE3 among women having in vitro fertilization with a median level of 0.92 MOM. Those fertilized with a donor egg (21) had significantly higher AFP and uE3 levels than when their own egg was used. Our results were confounded by differences in gravidity, but formally allowing for this factor did not materially change the findings. None of the observed effects is great enough to warrant routine adjustment of marker levels to allow for them. Moreover, women with positive Down's syndrome screening results can be reassured that this is unlikely to be due to them having had assisted reproduction.

Effect of gravidity on maternal serum markers for Down's syndrome.

The effect of gravidity on maternal serum alpha-fetoprotein (AFP), unconjugated oestriol (uE3), and human chorionic gonadotrophin (hCG) levels was investigated in 27,592 women being screened for Down's syndrome. There was no difference in the median AFP level in primigravid and multigravid women, but the median hCG level in multigravid women was 5.9 per cent lower than in those tested in their first pregnancy (P < 0.0001) and the median uE3 level was 3.9 per cent lower (P < 0.0001). Among multigravid women, there was no material difference in hCG levels according to the number of previous pregnancies or livebirths, whereas uE3 levels declined steadily with increasing numbers. Both markers declined with advancing maternal age: for hCG this was an independent effect, but for uE3 it was due to the correlation between age and gravidity. Allowing for these effects will not greatly alter the Down's syndrome screening detection and false-positive rates.

Solar activity cycle and the incidence of foetal chromosome abnormalities detected at prenatal diagnosis.

We studied 2001 foetuses during the period of minimal solar activity of solar cycle 21 and 2265 foetuses during the period of maximal solar activity of solar cycle 22, in all women aged 37 years and over who underwent free prenatal diagnosis in four hospitals in the greater Tel Aviv area. There were no significant differences in the total incidence of chromosomal abnormalities or of trisomy between the two periods (2.15% and 1.8% versus 2.34% and 2.12%, respectively). However, the trend of excessive incidence of chromosomal abnormalities in the period of maximal solar activity suggests that a prospective study in a large population would be required to rule out any possible effect of extreme solar activity.

In vitro radiosensitivity of fibroblasts from thyroid and skin cancer patients treated with X-rays for tinea capitis.

To investigate the hypothesis that persons who developed thyroid or skin cancer subsequent to scalp irradiation for tinea capitis are particularly sensitive to radiation, possibly because of a high frequency of ataxia-telangiectasia, we used an in vitro cell survival assay to evaluate radiosensitivity of their fibroblast cell strains. Study subjects were selected from a cohort of 10,834 Israelis irradiated during childhood for tinea capitis. Skin fibroblasts were obtained from thyroid and skin cancer patients (cases) as well as a sample of subjects who did not have cancer (controls). Fibroblasts were cultured and then loss of colony-forming ability as a result of acute X-irradiation was evaluated. Comparison of survival curve parameters (mean inverse of the slope and the dose needed to reduce colony survival to 10%) between 12 thyroid cancer and 12 control strains showed no differences (P > 0.5). A slightly increased radiation sensitivity of the skin cancer cases compared with their controls was observed. Although based on few subjects (14 cases and 11 controls), the findings were similar whether the mean inverse of the slope (P = 0.06) or the dose needed to reduce colony survival to 10% (P = 0.05) was evaluated. However, because of the small size of the study and potential errors inherent in survival assays, our finding that cell strains derived from patients who developed skin cancer exhibit enhanced radiosensitivity should be viewed as preliminary and interpreted cautiously.

Expanding multiple marker screening for Down's syndrome to include Edward's syndrome.

Information on maternal age and maternal serum alpha-fetoprotein, unconjugated oestriol (uE3), and human chorionic gonadotrophin (hCG) levels was used to investigate retrospectively the effect of estimating Edward's syndrome risk in women having multi-marker screening for Down's syndrome. The screened population comprised 15 pregnancies affected by Edward's syndrome, 15 with Down's syndrome and 5472 unaffected pregnancies. The use of all three markers to estimate Edward's syndrome risk would have led to the detection of 10-12 (67-80 per cent) cases with a false-positive rate of 0.3-0.6 per cent depending on the risk cut-off. A further case would have been detected as a result of screening for Down's syndrome alone. Similar results were obtained when the Edward's syndrome risk was based on uE3 and hCG only. These data suggest that extending Down's syndrome screening to include Edward's syndrome risk will yield a high detection rate with only a small increase in the false-positive rate.

An index for proportion of head size to body mass during infancy.

The index "head circumference (cm)3/body weight (g)" gave an almost constant average (about 10) and standard deviation (about 1) in more than 2000 children at birth and at 4, 10, and 18 months. Application of this index to the data previously published confirms that the average is almost constant throughout the period from birth to 18 months, irrespective of sex or race. Head circumference cubed and body weight correlate significantly. This index seems to be useful to assess the proportion of head size to body mass during infancy, and to contribute to early diagnosis of diseases such as hydrocephalus or microcephaly.

Human chorionic gonadotrophin and trisomy 18.

Estimation of maternal serum beta-hCG is used in conjunction with alpha-fetoprotein (AFP) and estriol (E3) for estimating the risk of Down syndrome (DS) affected fetuses. However, low hCG levels have not been regarded as having clinical significance. We report on 2 patients with trisomy 18 fetuses in whom antenatal screening showed extremely low hCG levels (0.05 and 0.15 MOM). Low hCG levels might indicate increased risk for trisomy 18 despite low estimated risk for DS.

Transcervical chorionic villi sampling: a comparison between the silver cannula and the Portex catheter.

The Portex catheter and the silver cannula are two of the most widely used biopsy devices for chorionic villus sampling. In a prospective randomized study we used these two devices alternatively in 168 women. Significantly more trophoblastic tissue was obtained with the silver cannula than with the Portex catheter (p less than 0.05) while significantly more failures to obtain villus tissue were recorded with the Portex cannula (8/84 with the silver cannula vs. 19/84 with the Portex cannula; p less than 0.05). In 27 cases where use of the device met with failure to obtain chorionic villi after three attempts the other instrument was then used in the same patient (combined group). Four pregnancies aborted spontaneously after the procedure (2.4%). Significantly more complications occurred in the 'combined' group (4/27 vs. 4/168, p less than 0.05). A higher yield of trophoblastic tissue is possible with the silver cannula than with the Portex catheter.