Amniotic fluid protease activity, protease inhibitory activity, and fetal lung maturity

Amniotic fluid acid protease and acid protease inhibitory activities were examined in normal pregnancies as a function of gestational age. The acid proteolytic activity of the amniotic fluid is almost constant during gestational weeks 16-29 (26 +/- 13 micrograms globin/ml/2 hrs, mean +/- SD, n = 64). The activity sharply increases after 29 weeks in a time-dependent fashion and reaches a value of 302 +/- 89 (mean +/- SD, n = 13) at 39-40 weeks gestation. Under standard conditions, the ability of amniotic fluid to inhibit bovine pepsin declined during gestation in a linear fashion from 44 +/- 13% (mean +/- SD, n = 36) at 16-18 weeks to 9 +/- 10% (mean +/- SD, n = 41) at 36-40 weeks. A correlation coefficient of r = 0.72 was found between pepsin inhibitory activity and gestational age. No consistent change was noted in the extent of inhibition of the endogenous acid protease throughout pregnancy. In 61 amniotic fluid samples, a correlation coefficient of r = 0.70 was found between acid protease activity and the lecithin/sphingomyelin (L/S) ratio. During the course of this study, five cases of respiratory distress syndrome (RDS) were diagnosed clinically. All five infants had a low protease activity (55 +/- 22 micrograms globin/ml/2 hr, mean +/- SD) as well as a low L/S ratio (0.68 +/- 0.20, mean +/- SD). In contrast, no case of RDS of the newborn was observed among 29 pregnancies with high protease activity and a high L/S ratio. The present observations may suggest a predictive value of amniotic fluid acid protease activity in assessment of fetal lung maturity.     

The effects of illicit drug use and HIV infection on sex hormone levels in women.

Drug use and HIV infection may affect sex hormone levels in women. One hundred and ninety-six women with and without a history of illicit drug use (50 HIV-negative and 148 HIV-infected), with regular menses, who never used antiretrovirals, were evaluated. Luteinizing hormone levels were significantly higher in women with a CD4 cell count <200/microl (p < 0.002). Current methadone use was associated with lower levels of total testosterone (p = 0.03) and higher levels of prolactin (p = 0.002); mean estradiol levels were 43% lower in women who used intravenous drugs (p < 0.001). Alcohol and crack cocaine use was not associated with sex hormone levels. Age, race, body mass index and degree of HIV immunosuppression were also associated with differences in sex hormone levels.     

Influence of metoprolol and cilazapril on blood pressure and on sleep apnea activity.

Up to 50% of hypertensive men are subject to sleep apnea (SA). With a prevalence in men of up to 10%, SA is a common illness and hypertension (HT) one of its early symptoms. It is important to have available a drug treatment that will effectively control blood pressure (BP) without exacerbating symptoms of SA. Twelve patients with SA and HT were investigated in a double-blind, comparative trial. Patients were randomly allocated to either metoprolol (M) 100 mg daily or cilazapril (C) 2.5 mg daily. Polysomnographic measurements under standardized conditions including intraarterial BP monitoring were taken on two consecutive nights each before and after the 1-week treatment. Values in the M group were (mean +/- 95% CI) systolic BP 161 +/- 2.1 vs. 148 +/- 2.2 mm Hg (p less than 0.01); diastolic BP 98 +/- 1.8 vs. 93 +/- 1.8 mm Hg (p less than 0.01); and HR 73 +/- 1.2 vs 65 +/- 1.1 beats/min (p less than 0.01). Corresponding figures for the C group were systolic BP 140 +/- 2.1 vs. 127 +/- 2.1 mm Hg (p less than 0.01); diastolic BP 95 +/- 1.7 vs. 78 +/- 1.7 mm Hg (p less than 0.01); and HR 82 +/- 1.1 vs. 79 +/- 1.2 beats/min (p less than 0.01). Whereas C reduced both BP and HR in all sleep phases, M produced no changes during REM sleep. SA activity was 45 (range 15-91) vs. 34 (range 2-57) apneas per hour of sleep in the M group and 54 (range 21-84) vs. 40 (range 8-72) apneas per hour in the C group (p less than 0.01). There were no changes in total sleep time or in the proportions of non-REM to REM sleep. Both M and C reduce nocturnal BP in SA patients, but the effect of C is seen in all sleep phases. C has a more favorable effect on the disturbed nocturnal blood pressure of SA patients.     

Inhibition of Human Mammary Cell Line Proliferation by Membrane Lectin-Mediated Uptake of Ha-ras Antisense Oligodeoxynucleotide

The Ha-ras oncogene promotes cell proliferation. Antisense oligonucleotides complementary to the ras gene sequence encompassing a mutated codon 12 selectively induce a cell proliferation inhibition. However, the concentration required to reach an effective inhibition is high due to the low efficiency of the oligonucleotide crossing through cell membranes, leading to a low concentration in the cytosol and/or the nucleoplasm. In the present paper, we show that anti-ras oligonucleotides linked to a glycosylated carrier, serum albumin bearing mannose 6-phosphate residues, are more efficient than free oligonucleotides or oligonucleotides bound to an unglycosylated carrier at inhibiting proliferation of a human tumor mammary cell line expressing the mutated Ha-ras. Using fluorescein-labeled neoglycoproteins and fluorescein-labeled oligonucleotides bound to neoglycoproteins, flow cytometry and confocal microscopy revealed that (i) these tumor cells express a membrane lectin specific for mannose 6-phosphate-bearing proteins, (ii) the membrane lectin actively mediates the uptake of macromolecules substituted with mannose 6-phosphate, and (iii) the fluorescein-labeled oligonucleotides bound to the neoglycoprotein accumulate in intracellular vesicles. Furthermore, with antisense oligonucleotides carried by the neoglycoproteins, the concentration required to inhibit cell proliferation is lower than that of the carrier-free antisense oligonucleotides.     

HLA and Down syndrome (DS): parents at the origin of the nondisjunction share no more HLA-A and -B antigens with their DS child than controls

Fifty couples and their children with Down syndrome (D.S.) were typed for HLA-A and HLA-B antigens and compared to 50 control families and 464 blood donors. The parental origin of the extra chromosome 21 was determined by cytogenetic methods. All individuals were caucasians and there was no history of consanguinity. No excessive HLA sharing was present in D.S. parents. The mothers of D.S. shared no more HLA antigens with their D.S. children than the control mothers with their normal children (14% vs. 18%). Thirteen of the fifty pairs (26%) (parent in whom the nondisjunction occurred and D.S. child) shared three HLA antigens at the A and/or B locus. This was not significantly higher than the proportion in the control group (12/50 or 24%). These data suggest that it is not the sharing of HLA-A and HLA-B antigens between the parents or between the parent who was the origin of the nondisjunction and the D.S. child that is related either to the occurrence of trisomy 21 zygotes or to prenatal survival of affected embryos and fetuses.     

Stability of parenteral midazolam in an oral formulation.

Midazolam is increasingly being used for oral sedation in pediatric dentistry. Unfortunately, it is available only as a parenteral formulation in Canada and the United States. Preparation of the parenteral solution for oral use is not uniform and leads the clinician to question the stability of this drug when used in conjunction with these vehicles. Therefore, the purpose of this study was to investigate the chemical stability of parenteral midazolam as an oral formulation to determine its expiry date. This was evaluated using a validated stability-indicating liquid chromatographic method. Midazolam was diluted in orange-flavored syrup to yield concentrations of 0.35, 0.64, and 1.03 mg/ml and then stored at room temperature. Samples were drawn on each of 9 study days (0, 1, 2, 6, 7, 9, 13, 21, and 102) and chromatographed. On each study day, solutions were inspected visually for changes in color, clarity, and appearance of particulate matter. Midazolam concentrations were considered within acceptable limits if they were not less than 90% of the initial concentration. Over the 102-day study period, there was no significant change in concentration in any of the solutions. On day 102, the remaining midazolam was within 7% of the day zero concentration. Therefore, these formulations of midazolam are stable at room temperature for a period of 102 days and would be suitable for clinical use.     

Two pathways of signal transduction are activated in the same cell by different cytokines.

NFS60, a murine leukemia cell line, responds to both interleukin 3 and 6 by proliferating, apparently by different signal transduction pathways. Although stimulation by both cytokines increases the uptake of 3H-arachidonic acid, the response to IL-6 was much faster. Furthermore, the effect of various arachidonic acid metabolites on the response to cytokine was different. PGE2 inhibited IL-6-induced proliferation and potentiated the response to IL-3. Additionally the G proteins which coupled the IL-3 and IL-6 receptor to the proliferative response are probably different, based on the ability of cholera toxin to inhibit the IL-3 but not the IL-6 response. These data are evidence of two pathways of signal transduction.     

Intracanalicular arachnoid cyst mimicking acoustic neuroma: CT and MRI.

A patient with a surgically proven intracanalicular arachnoid cyst was studied using computed tomography, magnetic resonance imaging, and air CT cisternography. The lesion had a similar radiographic appearance to acoustic neuroma and therefore, although rare, must be considered in the differential diagnosis of intracanalicular mass lesions. We report a case in which examination was performed, in evaluating the lesion, utilizing high-resolution air CT cisternography and magnetic resonance imaging (MRI).