Association of genetic polymorphisms with serum estrogens measured multiple times during a 2-year period in premenopausal women.

There is evidence that circulating estrogens are associated with breast cancer risk. In this study of premenopausal women, we explored the association of polymorphisms in genes in the estrogen synthesis and metabolism pathways with serum and urinary levels of estrone (E1) and estradiol (E2) and with the urinary ratio of 2-hydroxyestrone (2-OHE1)/16alpha-hydroxyestrone (16alpha-OHE1). This analysis included 220 women, who were participants in a 2-year randomized soy intervention. Blood specimens were collected in the luteal phase of the menstrual cycle an average of 4.4 times over 2 years. Overnight urinary specimens were collected on the same cycle day, only at baseline. Levels of E1, E2, 2-OHE1, and 16alpha-OHE1 were measured by enzyme immunoassays. The DNA samples were analyzed by PCR/RFLP for the COMT Val158Met, CYP1A1*2A, CYP1A1*2B, CYP1A2*1F, CYP1B1 Val432Leu, and CYP17 T27C polymorphisms. We applied mixed models to investigate the relations between genotypes and repeated serum hormone measurements and generalized linear models to assess associations between genotypes and urinary estrogen metabolites. The CYP1A2 C allele was significantly associated with lower serum E2 levels; in CC genotype carriers, serum E2 levels were 26.3% lower than in homo- and heterozygous common allele carriers combined (P = 0.01). CYP1A2*1F also affected the urinary 2-OHE1/16alpha-OHE1 ratio; carriers of the variant C allele had a markedly lower ratio than individuals with the AA genotype (1.37 versus 1.76; P = 0.002). These data suggest that CYP1A2*1F is associated with lower circulating levels of E2, and that it may be a susceptibility locus for breast cancer.     

Recent developments in human oocyte, embryo and blastocyst vitrification: where are we now?

The target of any cryopreservation procedure should be to ensure high survival rates of living cells after thawing. Two important parameters determine the success of any cryopreservation protocol: the manner in which cells regain equilibrium in response to cooling, and the speed of freezing (cooling rate). Slow-rate freezing protocols result in the formation of ice crystals during cooling and warming. Vitrification, in which high cooling rates in combination with a high concentration of cryoprotectant are used, does not produce any ice crystals during cooling and warming. However, there is a practical limit to the attainable cooling speed, and also a biological limit to the concentration of cryoprotectant tolerated by the cells during vitrification. Although post-warming survival depends on the species, the developmental stage and the quality of the embryos being vitrified, it seems clear that vitrification methods are increasingly successful and might be a better method than slow cooling procedures in the field of cryobiology. Many of the potential problems and benefits underlying vitrification as a method of choice for embryo cryopreservation in clinical embryology will be discussed in this review.     

Genetic polymorphisms in the estrogen receptor beta (ESR2) gene and the risk of epithelial ovarian carcinoma

Ovarian cancer is influenced by exogenous and endogenous estrogens as suggested by experimental and epidemiological evidence. Estrogen receptor beta is a predominant estrogen receptor in the normal ovary. Polymorphisms in the estrogen receptor beta gene (ESR2) might influence epithelial ovarian risk through regulation of cell proliferation and apoptosis. This population-based case–control study included 313 women with epithelial ovarian carcinoma and 574 controls, frequency-matched on age and ethnicity. Unconditional logistic regression was used to test associations of rs1271572, rs1256030, rs1256031, and rs3020450 ESR2 genotypes with ovarian cancer risk. Compared to homozygous common allele carriers, homozygous carriers of variant alleles for rs1271572 [odds ratio (OR) = 1.79, 95% confidence interval (CI):1.15–2.79, p global = 0.01] and rs1256030 [OR = 1.67, CI: 1.08–2.59, p global = 0.04], and women with haplotypes, including variant alleles of rs1271572, rs1256030, and rs1256031 SNPs [OR = 1.75, CI: 1.17–2.63, p global = 0.007], had significantly increased risk of ovarian carcinoma. The association of the rs1271572 genotype was strongest among women who had never used contraceptive steroids (p for interaction = 0.04). Our data suggest that ESR2 might be a susceptibility marker for epithelial ovarian cancer.     

Probability rates for different pregnancy outcomes in carriers of reciprocal chromosomal translocations involving chromosome 13

OBJECTIVES: The aim of study was to estimate the probability rates for unfavorable pregnancy outcomes in carriers of reciprocal chromosomal translocations involving 13 chromosome (RCT-13q). MATERIAL AND METHODS: We collected total empirical data about 232 pregnancies of 56 carriers coming from 28 pedigrees. RCT classification was based on classic cytogenetic methods for interpretation of breakpoint position. The probability rates of particular type of pathology related to the total number of pregnancies after ascertainment correction have been calculated with the help of Stengel-Rutkowski and Stene method. RESULTS: The risk figures for unbalanced offspring after 2:2 disjunction and adjacent-1 segregation for the whole group of pedigrees were calculated as 5.2 +/- 1.7% (9/173)--medium risk, for maternal (MAT) and paternal (PAT) carriers were about 6.2 +/- 2.3% (7/173) and 4.8 +/- 3.3% (2/42) respectively. Considering different segment lengths of 13q, similar values for shorter and longer segments were obtained [4.3 +/- 1.9% (5/115) for 13q21-->qter and 7.0 +/- 3.3% (4/58) for 13q12-->qter]. The risk figures for miscarriages as 36.4 +/-3.6% (63/173) and for stillbirths/early death as 4.6 +/- 31.6% (8/173) were obtained. The risk figures for unbalanced offspring after 3:1 disjunction were calculated as 7.7 +/- 7.45 (9/13). Conclusions: 1. Risk figures for different pregnancy outcomes are differ among particular forms of pathology. 2. Probability rate for unbalanced progeny at birth was calculated as a medium risk and similar values for carriers of different segments of 13q were obtained. 3. Probability rate for miscarriages was high but risk for stillbirths/early deaths of newborn was low. 4. No differences in values of rate for particular forms of pathology were found for maternal and paternal carriers of RCT-13q.     

Total and differential leukocyte counts percentiles in normal pregnancy

OBJECTIVE: To establish leukocyte count and leukocyte differential percentiles in normal uncomplicated pregnancy. STUDY DESIGN: This retrospective longitudinal study was performed in an outpatient facility for routine antenatal care. The study population comprised of 726 healthy women from the 5th to the 41st week of pregnancy. Altogether, there were 1749 complete blood count evaluations, of which 481 were in the 1st trimester, 687 in the 2nd trimester and 581 in the 3rd trimester. The total and differential leukocyte counts were determined by an automated cell counter. RESULTS: The leukocyte and neutrophil counts gradually and significantly increased form the 1st to the 3rd trimester. The monocyte count increase became significant only during the 3rd trimester. The eosinophil count did not significantly change throughout pregnancy. The basophil count significantly decreased during the 2nd trimester and returned to 1st trimester values during the 3rd trimester. CONCLUSION: In this study, we provide total and differential leukocyte counts' mean+/-S.D., minimal and maximal values, and the 3rd, 5th, 10th, 50th, 90th, 95th, and 99th percentiles for entire pregnancy and for each trimester separately. These reference values should prove useful for diagnostic and research purposes.     

Once a cesarean always a cesarean? A computer-assisted decision analysis

Objective A previous decision analysis models for two strategic choices for trial of labor or repeated cesarean after prior cesarean concluded that the degree of wish for an additional future pregnancy appeared to be a major determinant for choice between the two strategic options. We had extended the analysis model to stillbirth and hypoxic-ischemic encephalopathy in addition to placental complications while updating most of the outcomes in the decision tree. Study design A model was formulated using a decision tree based on reported probabilities for various outcomes and estimated utilities. The question asked was should trial of labor or repeated cesarean be performed after a prior cesarean, with a varying desire for an additional pregnancy. The highest expected outcome determines the preference of our model. Results Our model favors repeated elective cesarean (0.9947) over trial of labor (0.9917) after a previous cesarean and is the preferred approach. This approach was preferable irrespective of the probability of additional pregnancy. Conclusion In contrary to previous models, when taking into account the occurrence of a live infant birth, birth of an infant with hypoxic-ischemic encephalopathy stillbirth, neonatal death, abnormal placental implantation, hysterectomy and maternal death the preferred approach for women with previous cesarean is an elective repeated cesarean rather than trial of vaginal delivery.     

STUDIES ON THE MECHANISM OF IMMUNITY IN TUBERCULOSIS : THE R?LE OF EXTRACELLULAR FACTORS AND LOCAL IMMUNITY IN THE FIXATION AND INHIBITION OF GROWTH OF TUBERCLE BACILLI

1. The fate of bacilli of reinfection at the portal of entry and in metastatic foci, and also the associated host responses, are essentially similar in rabbits and guinea pigs. 2. However, in the guinea pig tubercle bacilli of reinfection are more effectively fixed at the portal of entry than in the rabbit. 3. The guinea pig fixes at the site of reinfection unrelated substances, such as trypan blue and agar particles, more effectively than the rabbit. 4. At the site of a local non-specific inflammation precipitins from the circulating blood accumulate in higher concentration in tuberculous guinea pigs than in tuberculous rabbits. 5. These differing fixing capacities of the two species are associated with differences of extracellular character in the inflammation resulting from reinfection. (a) In the guinea pig, whose tissues are highly sensitized and greatly injured by the tubercle bacillus, the lymphatics adjoining the site of reinfection become thrombosed. In the rabbit whose tissues are moderately sensitized and less injured by the tubercle bacillus the corresponding lymphatics remain open. (b) In the guinea pig the fibrinous network at the site of inflammation forms a fine sieve-like structure. In the rabbit this network forms a coarse sieve-like barrier. 6. In rabbits and guinea pigs primarily infected, the destruction of tubercle bacilli takes place first and most extensively at the portal of entry. At this time they are less effectively destroyed in the nearest metastatic foci. Simultaneously they are still growing without hinderance in such foci in remote internal organs. 7. The cell-free body fluids of normal animals support the growth of tubercle bacilli in vivo. The body fluids of tuberculous animals under the same conditions are bacteriostatic for this microorganism. 8. Tubercle bacilli often multiply by preliminary subdivision into non-acid-fast granules, from which the acid-fast rods sprout. This confirms the work of Kahn.     

ON THE MECHANISM OF IMMUNITY IN TUBERCULOSIS : THE HOST-PARASITE RELATIONSHIP UNDER THE CONDITIONS OF A LOCALIZED AGAR FOCUS OF INFECTION AND THE GENERALIZATION OF THE DISEASE IN NORMAL AND IMMUNIZED RABBITS

1. There is an extracellular factor which inhibits the growth of tubercle bacilli in immunized rabbits. 2. Extracellular factors localize carbon particles, trypan blue and tubercle bacilli at the site of introduction to a greater extent in the immunized than in the normal animal. 3. This greater fixation is brought about by an increase in the density and extent of the fibrin barrier formed about the focus of the immunized animal. The more pronounced in vivo agglutination of tubercle bacilli and carbon particles in the vaccinated or tuberculous rabbit also tends to immobilize them in the tissues. 4. The growth inhibitory and localizing agents are effective in the fixation of small doses on reinfection at the portal of entry. 5. With large doses on reinfection, the increased lymph flow resulting from the intensified inflammation in the immunized animal brings about a more rapid dissemination of the bacilli to the draining lymph nodes than in the normal animal. 6. The most significant factor in immunity is the increased capacity of the rapidly mobilized mononuclear phagocytes to destroy tubercle bacilli. The impotent polymorphonuclear leukocytes quickly disappear from the site of reinfection. 7. The invading bacilli that reach the draining lymph nodes of the immunized animal are retarded in multiplication or destroyed by these phagocytes. 8. Vaccination of rabbits with BCG brings into play the factors tending to immobilize the bacilli of reinfection, inhibit their growth and destroy them with a resulting significant immunity. 9. A virulent primary infection affords a greater immunity than one of low virulence and the host reactions are expressed by a quantitative increase in those immunity factors which operate in a vaccinated animal.