Raja W. Abdul-Karim

The regulatory effect of estrogens on fetal growth

Abstract The influence of estrogen on placental and fetal growth was studied. White New Zealand pregnant rabbits were rendered estrogen deficient by a bilateral oophorectomy on the tenth day of gestation and given a daily dose of 5 mg. of progesterone intramuscularly up to the time of delivery. A second group similarly oophorectomized received the same dose of progesterone plus 2 μg estradiol-17β daily. A third group was sham operated and served as controls. Does from each of these groups were delivered at 21, 27, and 31 days of gestation. The total number of fetuses per litter as well as the number and weights of the live-born and their placentas were recorded in each instance. The results showed that in the estrogen-deficient pregnancies there was a significant increase in placental weight and in the placental to live-born weight ratio at all the periods of gestations studied. Live-born weight was also increased in the 27 and 31 day periods. An increase in stillbirth rate occurred in the estrogen-deficient group. It is concluded that estrogens regulate placental (and consequently fetal) size by exerting an inhibitory effect on placental growth. The mechanism by which this may be brought about is discussed.Abstract The influence of estrogen on placental and fetal growth was studied. White New Zealand pregnant rabbits were rendered estrogen deficient by a bilateral oophorectomy on the tenth day of gestation and given a daily dose of 5 mg. of progesterone intramuscularly up to the time of delivery. A second group similarly oophorectomized received the same dose of progesterone plus 2 μg estradiol-17β daily. A third group was sham operated and served as controls. Does from each of these groups were delivered at 21, 27, and 31 days of gestation. The total number of fetuses per litter as well as the number and weights of the live-born and their placentas were recorded in each instance. The results showed that in the estrogen-deficient pregnancies there was a significant increase in placental weight and in the placental to live-born weight ratio at all the periods of gestations studied. Live-born weight was also increased in the 27 and 31 day periods. An increase in stillbirth rate occurred in the estrogen-deficient group. It is concluded that estrogens regulate placental (and consequently fetal) size by exerting an inhibitory effect on placental growth. The mechanism by which this may be brought about is discussed.

Low-Density Lipoprotein Stimulated Peroxide Production and Endocytosis in Cultured Human Endothelial Cells: Mechanisms of Action

The effects of arachidonic acid metabolism and NADPH oxidase inhibitor on the hydrogen peroxide (H2O2) generation and endocytotic activity of cultured human endothelial cells (EC) exposed to atherogenic low-density lipoprotein (LDL) levels have been investigated. EC were incubated with 240 mg/dl LDL cholesterol and cellular H2O2 production and endocytotic activity measured in the presence and absence of the arachidonic acid metabolism inhibitors, indomethacin, nordihydroguaiaretic acid, and SKF525A, and NADPH oxidase inhibitor, apocynin. All inhibitors, with the exception of indomethacin, markedly reduced high LDL-induced increases in EC H2O2 generation and endocytotic activity. EC exposed to exogenously applied arachidonic acid had cellular functional changes similar to those induced by high LDL concentrations. EC incubated with 1-25 uM arachidonic acid had increased H2O2 production and heightened endocytotic activity. Likewise, EC pre-loaded with [3H]arachidonic acid when exposed to increasing LDL levels (90-330 mg/dl cholesterol) had a dose-dependent rise in cytosolic [3H]arachidonic acid. The phospholipase A2 inhibitors, 4-bromophenacyl bromide and 7,7-dimethyleicosadienoic acid, markedly inhibited H2O2 production in EC exposed to 240 mg/dl LDL cholesterol. These findings suggest that arachidonic acid contributes mechanistically to high LDL-perturbed EC H2O2 generation and heightened endocytosis. Such cellular functional changes add to our understanding of endothelial perturbation, which has been hypothesized to be a major contributing factor in the pathogenesis of atherosclerosis.

Influence of estradiol-17β on the acetylcholine content of the lung in the rabbit neonate

The influence of estradiol-17 β on the acetylcholine content of the lungs was studied in rabbit neonates born to oophorectomized mothers. It was found that 10μg of crystalline estradiol-17 β administered subcutaneously to newborn rabbits doubled the acetylcholine content of their lungs as compared to littermate controls. These findings suggest a mechanism whereby estradiol-17 β may affect the degree of vasodilatation in the vessels of the lungs.

The influence of estradiol-17β on cholinesterase activity in the lung

Abstract Estradiol-17β (2 mg. per day) was administered to healthy adult oophorectomized white New Zealand rabbits for a period of 6 days. The rabbits were then anesthetized and the left lung was removed. The total protein content, wet to dry weight ratio, and cholinesterase (ChE) activity were determined. Compared to the controls there was a significant increase in ChE activity in the lungs of the estrogen-treated rabbits, when expressed on the basis of wet weight, dry weight, or protein content of the tissues. It is suggested that this increase in ChE reflects an elevated acetylcholine concentration.

Efficacy of maternal screening and therapy in the prevention of Chlamydia infection of the newborn

SummaryRoutine cervical cultures for chlamydia were obtained during the third trimester of pregnancy to identify infected mothers whose infants may also be infected. The effectiveness of maternal erythromycin therapy in preventing disease due to chlamydia among infants born to these women was also assessed. Clinical outcome of treated mothers and infants was compared to that of untreated subjects. Of 1082 women who were cultured, 85 (7.8%) were positive for chlamydia. Erythromycin therapy was prescribed for 38 of these women. Nasopharyngeal/conjunctival chlamydia cultures were obtained from 16 infants of culture-positive, treated mothers and 21 infants of culture-positive, untreated mothers. None of the infants born to culture-positive, treated mothers developed infection with chlamydia, while five of 21 infants of untreated mothers (p<0.04) were culture-positive and symptomatic (four with conjunctivitis, one with pneumonia). On follow-up of the infants born to chlamydia-positive mothers, there was no evidence that chlamydia-infected infants had more frequent episodes of upper respiratory infection and otitis media during the first six months of life. This study demonstrated that diagnosis and treatment of cervical chlamydia infection during the third trimester of pregnancy provides a practical approach to the prevention of infection in the newborn.ZusammenfassungBei Schwangeren wurden im dritten Trimenon routinemäßig Chlamydien-Kulturen von der Zervix angelegt, um mit der Infektion bei der Mutter auch das Infektionsrisiko des Neugeborenen zu erfassen. Auch wurde geprüft, ob die Behandlung infizierter Mütter mit Erythromycin eine Chlamydieninfektion beim Neugeborenen verhindern kann. In einer Vergleichsstudie wurde der klinische Verlauf der behandelten und nicht behandelten Mütter und deren Kinder kontrolliert. Bei 85 von 1082 kulturell untersuchten Frauen (7,8%) wurden Chlamydien nachgewiesen. 38 dieser Frauen wurde Erythromycin verordnet. In 16 Fällen waren die Neugeborenen von behandelten Frauen mit positiven Chlamydienkulturen in Kulturen aus Nasopharynx- und Konjunktivalabstrichen ebenfalls positiv. In der Gruppe unbehandelter Frauen mit positiven Kulturen waren 21 Kinder positiv. Die Kinder der behandelten, positiven Mütter bekamen in keinem Fall eine Injektion, während bei fünf der 21 positiven Kinder unbehandelter Mütter Infektionssymptome (in vier Fällen Konjunktivitis, in einem Fall Pneumonie) auftraten (p<0,04). Kontrolluntersuchungen, die während der ersten sechs Lebensmonate durchgeführt wurden, deckten bei den Kindern mit Chlamydieninfektionen keine höhere Inzidenz an oberen Atemwegsinfektionen oder Otitis media auf als bei den übrigen Kindern. Die Studie zeigt, daß die Behandlung der zervikalen Chlamydieninfektion während des letzten Trimenon eine brauchbare Methode zur Verhütung von Infektionen bei Neugeborenen ist.

The effect of cis- and trans-clomiphene citrate on the collagen content of fetal bone

cis- and trans-Clomiphene citrate were administered im to pregnant rabbits from day 21 to day 26 of gestation. Seven rabbits received 15 mg/kg and 6 rabbits 25 mg/kg of the cis-isomer daily. trans-Clomiphene citrate was given to 4 rabbits in a daily dose of 10 mg/kg and to 8 rabbits in a dose of 15 mg/kg; 8 rabbits served as controls. The rabbits were delivered by hysterotomy on day 27, and the fetuses and placentas were weighed. The femurs from liveborns were dissected free of soft tissue, and the wet and fat-free dry weights were recorded. The collagen and total ash of the femurs were determined. The only significant differences between the control and experimental rabbits occurred when trans-clomiphene 15 mg/kg was used. With this dose of trans-clomiphene, fetal weight was decreased from 25.5 ± 2.3 g to 20.2 ± 5.2 g (p = 0.02) and the collagen to dry weight ratio of bone from 18.6 ± 2.0 to 13.9 ± 2.9 (p < 0.01). The collagen to ash ratio in the trans-clomiphene 15 mg/kg treated group was 0.32 ± 0.07 compared to 0.5 ± 0.09 in the controls (p < 0.005). It is suggested that the changes in fetal weight and bone composition under the influence of the trans-isomer are due to its estrogenic properties.

Protein Kinase C Inhibitors Prevent Cultured Human Endothelial Cell Stress Fiber Formation, but not Heightened Endocytosis

In order to study the signal transduction mechanism of endothelial perturbation, the effects of phorbol 12-myristate 13-acetate (PMA) and phorbol 12,13-dibutyrate (PDBu), both protein kinase C (PKC) activators, on cultured human endothelial cell (EC) hydrogen peroxide (H2O2) generation, endocytotic activity, and cytoskeletal structure have been investigated. EC were incubated with 1-100 nM PMA, or PDBu, and cellular H2O2 generation and endocytotic activity measured. PMA and PDBu exposure caused dose-dependent rises in EC H2O2 production. Likewise, EC incubated with PMA and PDBu had dose-related endocytosis increases. Cytoskeletal inspection of 10 nM PMA-perturbed EC revealed structural remodeling with stress fiber formation. Similar cellular functional changes occur in EC exposed to high low-density lipoprotein (LDL) concentrations. Protein kinase C (PKC) inhibition with 1-(5-isoquinolinesulfonyl)-2-methylpiperazine dihydrochloride (H-7) prevented cytoskeletal remodeling in PMA-stimulated EC. In differenc...

Appraising a clinical journal article in obstetrics and gynecology

Although some physicians have the opportunity to participate in a journal club during residency, many infrequently receive formal instruction on how to critically evaluate a journal article. Systematic guidelines for appraising a clinical journal article are presented and illustrated with examples. Considering each guideline in its respective order may lead to a better understanding of what the literature may offer ones practice.

Uterine hemorrhage due to arteriovenous malformation in a teenage girl: Diagnosis and management

Abstract An 18-year-old girl was evaluated because of severe uterine bleeding. The onset of each episode was abrupt. The bleeding failed to respond to steroidal oral contraceptives. Uterine curettage revealed a benign endometrium. Endocrine and coagulation studies were normal. Arteriovenous malformation was diagnosed by hysteroscopy and angiography studies. Retrograde femoral catheterization and embolization of the malformation did not totally alleviate the bleeding. The patient elected a hysterectomy rather than another embolization procedure.

The influence of ethamoxytriphetol on the collagen and calcium contents of the femurs of rabbit fetuses

Ethamoxytriphetol, 1-(P-2-diethylaminoethoxyphenyl)-1-phenyl-2-methoxyphenyl ethanol (MER-25), was administered to a group of 6 pregnant rabbits in a daily dose of 25 mg/kg body weight. Eight pregnant rabbits received a daily dose of sesame oil and served as controls. All injections were begun on day 21 of gestation and carried through day 26. All the rabbits were delivered by cesarean section on day 27. The femurs of the liveborn were dissected free of soft tissue and the wet and fat-free dry weights were recorded. The collagen and calcium contents were analyzed. In the treated group receiving the antiestrogen, MER-25, collagen was significantly reduced when expressed as percent of both the wet weight (2.85 ± 0.54 vs. 3.76 ± 0.36) and the fat-free dry weight (16.3 ± 1.3 vs. 18.2 ± 1.1). The calcium to wet weight ratio in the MER-25 treated group was less than that of the controls (2.63% ± 0.49 vs. 3.42% ± 0.50), whereas the calcium as percent of the fat-free dry weight of the bone was not significantly different (15.1 ± 2.1 vs. 16.6 ± 2). It is concluded that ethamoxytriphetol retards fetal bone development and produces a decrease in collagen formation in fetal bone, but no disturbance in bone mineralization.