Boleslav Goldman

The use of aspirin to prevent pregnancy-induced hypertension and lower the ratio of thromboxane A2 to prostacyclin in relatively high risk pregnancies

We carried out a prospective, randomized, double-blind, placebo-controlled study to investigate the capacity of aspirin to prevent pregnancy-induced hypertension and to alter prostaglandin metabolism. A total of 791 pregnant women with various risk factors for pre-eclamptic toxemia were screened with use of the rollover test (a comparison of blood pressure before and after the woman rolls from her left side to her back) during week 28 or 29 of gestation. Of 69 women with abnormal results (an increase in blood pressure during the rollover test), 65 entered the study and were treated with a daily dose of either aspirin (100 mg; 34 women) or placebo (31 women) during the third trimester of pregnancy. The number of women in whom pregnancy-induced hypertension developed was significantly lower among the aspirin-treated than among the placebo-treated women (4 [11.8 percent] vs. 11 [35.5 percent]; P = 0.024); the same was true for the incidence of preeclamptic toxemia (1 [2.9 percent] vs 7 [22.6 percent]; P = 0.019). The mean ratio of serum levels of thromboxane A2 to serum levels of prostacyclin metabolites after three weeks of treatment decreased by 34.7 percent in the aspirin-treated group but increased by 51.2 percent in the placebo-treated group. No serious maternal or neonatal side effects of treatment occurred in either group. We conclude that low daily doses of aspirin taken during the third trimester of pregnancy significantly reduce the incidence of pregnancy-induced hypertension and pre-eclamptic toxemia in women at high risk for these disorders, possibly through the correction of an imbalance between levels of thromboxane and prostacyclin.

Prevalence of glucocerebrosidase mutations in the Israeli Ashkenazi Jewish population.

Gaucher disease is the most prevalent inherited disease among Ashkenazi Jews. It is very heterogeneous due to a large number of mutations within the glucocerebrosidase gene, whose impaired activity is the cause for this disease. Aiming at determining Gaucher carrier frequency among the Ashkenazi Jewish population in Israel, 1,208 individuals were molecularly diagnosed for six mutations known to occur among Ashkenazi Jewish Gaucher patients, using the newly developed Pronto™ Gaucher kit. The following mutations were tested: N370S, 84GG, IVS2+1, D409H, L444P, and V394L. Molecular testing of these mutations also allows identification of the recTL allele. The results indicated that Gaucher carrier frequency is 1:17 within the tested population. The prevalence of N370S carriers is 1:17.5. This implies that ˜1:1225 Ashkenazi Jews will be homozygous for the N370S mutation. Actually, in our study of 1,208 individuals one was found to be homozygous for the N370S mutation. The actual number of known Ashkenazi Jewish Gaucher patients with this genotype is much lower than that expected according to the frequency of the N370S mutation, suggesting a low penetrance of this mutation. Results of loading experiments in cells homozygous for the N370S mutation, as well as cells homozygous for the L444P and the D409H mutations, exemplified this phenomenon. Hum Mutat 12:240–244, 1998.

Maternal serum lipid profile in pregnancies complicated by hypertensive disorders

Plasma lipoprotein, cholesterol and triglycerides were determined in 34 hypertensive pregnant patients and in 17 healthy full term pregnant women. Pregnancy induced hypertension was diagnosed in 21 patients and chronic hypertension in the remaining 13 women. Serum triglyceride levels were significantly elevated in the hypertensive patients. This elevation was not influenced by either the severity or the etiology of the hypertension. The total cholesterol/HDL and the LDL/HDL ratios were significantly elevated in the severely hypertensive patients, and furthermore the LDL/HDL ratio was elevated in patients receiving anti-hypertensive treatment. The lipid profiles found in hypertensive pregnant patients could be associated with enhancement of pathological lipid deposition in predisposed vessels such as the uterine spiral arteries. Furthermore, the hypertriglyceridemia found in the hypertensive patients may be associated with the hypercoagulability reported in pregnancy induced hypertension.

Motivations, perceptions and interpersonal differences associated with interest in genetic testing for breast cancer susceptibility among women at high and average risk

Abstract Womens intentions regarding genetic testing for breast cancer susceptibility were the focus of the present research. We explored motives behind intentions to be tested for genetic susceptibility to breast cancer; the relationships between risk status and risk perceptions and intentions to be tested; and individual differences in coping styles associated with intentions to be tested. Results on 150 women (54 at risk and 96 average risk) showed that: most women would consider being tested; different factors count for reasons for and against testing; motivations to be tested differ between the two risk groups; “unrealistic optimism” was observed only among women at average-risk; intentions to be tested were related to risk perceptions and to individual differences (in desire for control, external health locus of control, preferences for self-treatment, preferences for medical information, and need for closure) only among women at average-risk. Practical and theoretical implications of these finding...

Patients' information needs and decision-making processes: what can be learned from genetic counselees?

This field study investigated the information needs and decision-making strategies of 161 genetic counselees interviewed just prior to counseling. Patients were interested mostly in information about the outcomes and consequences of the alternative options at their disposal and about measures to defuse the risks. They wanted mainly information stated with certainty and were less interested in probability information. There was no difference in the search for information between the alternative eventually chosen and the one not chosen. There was a difference, however, among types of decisions and the interest in the various categories of information. These findings were interpreted within the theoretical model of decision making in natural risky situations (O. Huber, 1997). Practical implications for shared medical decision making are presented.

Enhancement of the immune system of chemotherapy-treated cancer patients by simultaneous treatment with thymic extract, TP-1

SummaryThirty patients with incurable gastrointestinal cancer were treated in a randomized clinical trial, either with combination chemotherapy (5-fluorouracil, vincristine, and methyl-CCNU) or with the same chemotherapy and the thymic extract TP-1. T-lymphocyte counts slowly and steadily, increased in the TP-1-treated patients over a period of 4–5 months, in contrast to decreasing counts in the patients treated by chemotherapy only. The changes in both groups were significantly different from pretreatment counts (P<0.01). Skin tests for primary sensitization with DNCB were converted to positive or improved after TP-1 treatment (P<0.05 against control patients). In conclusion, TP-1 had a progressively accumulating effect on T-cell lymphopoiesis and activity (skin tests), which was strong enough to overcome chemotherapy-induced immunosuppression without any appreciable side effects.

The trisomy 4p syndrome: A case report

Partial trisomy of the short arm of chromosome 4 is considered to be a rare chromosomal disorder. Its clinical and dermatoglyphic features tend to make it a clinically recognizable syndrome. This paper describes a 2 year-old female child with the characteristic findings of frontal bossing, deep-set eyes, broad nasal bridge giving the appearance of hypertelorism, wide nares, midfacial hypoplasia, large dysplastic ears, prognathism and various hand and foot malformations.Chromosomal studies showed her to be trisomic for the distal two-thirds of the short arm of number 4. The etiology of this chromosomal aberration in most instances is unknown, but may occur as a result af an unbalanced translocation in one of the parents as in the case reported here.

Fluorescence polarization of serum lipids in pregnancies complicated by hypertensive disorder

Hypertensive disorders in pregnancy are associated with an increase in serum lipid fractions. Fluorescence Polarization (FP) of lipids in the serum of 80 hypertensive pregnant patients at full term was compared to measurements in a control group of 71 healthy pregnant volunteers. In addition, the FP values were correlated with measurements of serum lipid fraction in 34 hypertensive and 17 control patients. Both chronic hypertension and pregnancy induced hypertensive (PIH) subjects had significantly reduced serum FP values compared to the control group. This difference was however present only in the severely hypertensive patients, independent of the etiology of this disorder. Highly significant correlations were present between the FP values and serum level of Triglycerides r = -0.85, Very Low Density Lipoprotein r = -0.76, and Low Density Lipoprotein r = 0.53. Serum FP values appear to reflect the change in the lipoprotein pattern present in pregnant patients with hypertensive disorders. This change appears to reflect the severity of the condition rather than the etiology of the hypertension.

The effect of thyroxine and corticosteroids upon amniotic fluid fluorescence polarization: a randomized controlled study

The efficacy of glucocorticoid and intra amniotic thyroxine therapy on fetal lung maturity were compared in a randomized prospective clinical trial. Eighty two patients received either intra amniotic thyroxine (n = 36), or intra muscular Dexamethasone (n = 46). The Fluorescence Polarization (FP) of amniotic fluid measured prior to and one week following treatment were similar in the two groups. The rate of decrease in FP value per unit of time (dFP/dt) was identical in the T4 and corticosteroid treated patients and the proportion of immature FP values obtained was similar in the two groups. The effect of thyroxine therapy was more pronounced in pregnancies above 33 weeks gestation. Intra amniotic thyroxine therapy appeared to be as effective as glucocorticoids for the enhancement of fetal lung maturity. This therapeutic modality may be of particular use on pregnant subjects in whom a relative contra indication for the administration of steroids exists.

Amniotic Fluid α-Fetoprotein Levels and Fetal Chromosomal Abnormalities

406 midtrimester amniotic fluid samples were examined for Α-fetoprotein (AFP) levels and fetal karyotyping. 44 cases with Down syndrome, 12 with Klinefelter syndrome and 14 with other chromosomal