Human fibroblast tissue factor is inhibited by lipoprotein-associated coagulation inhibitor and placental anticoagulant protein but not by apolipoprotein A-II

Studies of proteins that inhibit tissue factor activity have generally been conducted using either an extracted tissue homogenate ("thromboplastin") or tissue factor protein reconstituted into phospholipid vesicles rather than with tissue factor expressed in cell membranes (its physiological environment). In the present study, a human fibroblast cell strain was used to evaluate the effects of lipoprotein associated coagulation inhibitor (LACI), placental anticoagulant protein (PAP), and apolipoprotein A-II (apo A-II) on human tissue factor in cell membranes. LACI was tested from 7.8 to 500 pmol/L on fibroblasts cultured at cell densities ranging from 3,500 to 9,925 cells/well, and caused a progressive inhibition of tissue factor activity. PAP was tested from 3.9 nmol/L to 1 mumol/L at cell densities ranging from 4,500 to 15,400 cells/well and caused up to 83% inhibition of tissue factor activity. Inhibition by these proteins appeared to be influenced by cell density as well as whether the cells were intact or disrupted. Apo A-II, up to 1 mumol/L, did not inhibit the tissue factor activity of intact or disrupted fibroblasts at any cell density examined even though it did inhibit the activity of tissue factor in phospholipid vesicles. Of these inhibitors of tissue factor-dependent activation of factor X, LACI was the most effective in suppressing the generation of factor Xa activity. The effects obtained with apo A-II are clearly dependent on the nature of the tissue factor preparation with which it is tested. The disparity between the inhibitory effect of apo A-II on the activity of tissue factor reconstituted into lipid vesicles and the absence of effect on the activity of tissue factor remaining in cell membranes serves to reemphasize the necessity of reexamining results obtained with model systems using as nearly physiological reagents as possible.     

Transdermal scopolamine decreases nausea and vomiting following cesarean section in patients receiving epidural morphine

The authors evaluated the antiemetic properties of transdermal scopolamine (TDS) in healthy patients undergoing elective cesarean section and receiving epidural morphine for postoperative analgesia. Prior to administration of anesthesia, 203 patients had either TDS or a placebo study patch applied behind one ear. All patients were hydrated with lactated Ringer's solution iv and given 2.0% lidocaine with 1:200,000 epinephrine epidurally for surgical anesthesia. Following delivery of the infant, 4 mg of morphine sulphate was injected through the epidural catheter. After the operation patients were evaluated by "blinded" observers at 2, 4, 6, 8, 10, 24, and 48 h for nausea, vomiting, retching, pain relief, itching, and adverse effects. In addition, medications received were noted. No differences were found between the groups in terms of severity or incidence of pain, or requests for analgesic or antipruritic medication. Although there was no difference between the groups in the first 2 h, patients with TDS had significantly less nausea, vomiting, and retching than patients in the placebo group in each time interval between 2 and 10 h. Additionally, the TDS group required less antiemetic medication. There was no difference in the frequency of retching or vomiting between groups. Side effects were minimal and equal in both groups. The authors conclude that TDS results in a decreased incidence of nausea and vomiting in patients who have delivered by cesarean section and received epidural morphine. TDS appears safe for continuous antiemetic administration.     

Partial 18 trisomy (with 47 chromosomes) resulting from a familial maternal translocation.

A newborn female infant presented with the classical picture of 18 trisomy syndrome. Her karyotyping was 47,XX,+der(18)t(12;18)(q24;q21)mat. The mother was a balanced reciprocal translocation carrier and so too was one of the two maternal uncles of the proposita, indicating that the translocation was already present in one of the grandparents who were not available for examination. This family suggests that triplication of the distal part of the long arm of chromosome 18 is not necessary to produce Edwards' syndrome.     

Familial translocation 15/22. A possible cause for abortions in female carriers

A familial Robertsonian translocation 15/22 was ascertained through a female carrier whose four pregnancies ended in missed abortions. Eleven 15/22 translocation carriers were detected in three generations among 23 family members investigated. The four proven female carriers, apart from the proposita, have miscarried seven out of 14 pregnancies. The kindred suggests that the 15/22 translocation in female carriers may cause an increased risk for miscarriage.     

Chromosomal breakage in normal and fragile X subjects using low folate culture conditions.

To investigate whether the fragile X syndrome is associated with a generalised chromosomal instability, we compared the frequency and distribution of chromosomal breakage in lymphocytes grown in low folate medium from normal subjects and from patients with the syndrome. Although low folate conditions increased the rate of chromosome breakage, no difference in frequency or distribution of chromosomal breakage was found between the two groups. This suggests that the fragile X syndrome is not associated with a generalised chromosome instability expressed in folate deficient medium and assessed in terms of chromosomal breakage.     

Comparison between testosterone oenanthate-induced azoospermia and oligozoospermia in a male contraceptive study. IV. Suppression of endogenous testicular and adrenal androgens

Administration of supraphysiological doses of testosterone to normal men causes inhibition of spermatogenesis, but while most become azoospermic, 30-55% maintain a low rate of spermatogenesis. We have investigated whether there are differences in endogenous androgen production, of testicular and adrenal origin, which may be related to the degree of suppression of spermatogenesis. Thirty-three healthy Caucasian men were given weekly i.m. injections of 200 mg testosterone oenanthate (TE), 18 became azoospermic, while 15 remained oligozoospermic. Urinary excretion of epitestosterone, a specific testicular product, was reduced to <10% of pretreatment values, with no differences between the groups. Similar results were obtained for other markers of testicular steroidogenesis. Urinary and plasma adrenal androgens were also reduced during TE treatment: a statistically significant decrease in both (P < 0.001 and P < 0.05 respectively) was seen in the azoospermic but not oligozoospermic responders. These results suggest that testicular steroidogenesis is decreased to <10% by the administration of supraphysiological doses of exogenous testosterone. Differences in the degree of ongoing steroidogenesis in the testis do not appear to account for incomplete suppression of spermatogenesis, thus differences in androgen metabolism may underlie this heterogeneous response. A small but significant reduction in secretion of adrenal androgens was also detectable, the relevance of which is unclear.