XRCC3 is required for efficient repair of chromosome breaks by homologous recombination.

XRCC3 was originally identified as a human gene able to complement the DNA damage sensitivity, chromosomal instability and impaired growth of the mutant hamster cell line irs1SF. More recently, it has been cloned, sequenced and found to bear sequence homology to the highly conserved eukaryotic repair and recombination gene RAD51. The phenotype of irs1SF and the identification of XRCC3 as a member of the RAD51 gene family have suggested a role for XRCC3 in repair of DNA damage by homologous recombination. Homologous recombinational repair (HRR) of a specifically induced chromosomal double-strand break (DSB) was assayed in irs1SF cells with and without transient complementation by human XRCC3. Complementation with XRCC3 increased the frequencies of repair by 34- to 260-fold. The results confirm a role for XRCC3 in HRR of DNA DSB, and the importance of this repair pathway for the maintenance of chromosomal integrity in mammalian cells.

Psychological factors and bleeding frequency in hemophilia. Lack of association.

To assess the role of psychological factors in hemophilic bleeding frequency we studied 51 severe hemophilic men above the age of 16 who were on home treatment and under care by five cooperating comprehensive hemophilia centers. Psychological status was assessed by three instruments [Minnesota Multiphasic Personality Inventory (MMPI); Holmes-Rahe Life Events Inventory (LEI); and Daily Hassles Scales], and bleeding episodes were recorded for a 3 month period. A multiple regression analysis showed no association between bleeding frequency and MMPI subgroups, LEI, or the frequency of hassles. There were no significant differences between hemophiliacs with high bleeding frequencies and those with low bleeding frequencies on any of the scales or tests. The MMPI scale scores and profiles and the Holmes-Rahe Life Event scores were not significantly different from norms. These data suggest that, at least among patients under comprehensive care and on home treatment, the psychological factors measured by these instruments are not related to the bleeding frequency of most hemophiliacs.

Survival of transfused factor VIII in hemophilic patients treated with epsilon aminocaproic acid.

The effect of EACA (epsilon aminocaproic acid) on the survival of factor VIII (F. VIII, antihemophilic factor, AHF) concentrates after infusion in hemophilic subjects was studied using two F. VIII preparations: an intermediate purity "cryoglobulin" and a high purity glycine-precipitated concentrate. In vivo recoveries of F. VIII with both concentrates were found to be close to the values predicted on the basis of concentrate potencies assayed prior to infusion, but not if the labeled potency was used in the calculation. Control studies showed similar first and second phase half-life times and half-disappearance times when the two F. VIII preparations were infused, and both preparations were found to follow a biphasic disappearance curve. The biological half-life (second phase rate of disappearance) was 12 to 13 hours. The administration of EACA in conjunction with the F. VIII concentrates did not prolong the half-life times (first or second phase) or the half-disappearance times.

Plasma volume, electrolyte, and coagulation factor changes following intra-amniotic hypertonic saline infusion.

PIP: To determine the relationship of coagulapathy to saline infusions for abortion, plasma volume, electrolyte, and coagulation factors were studied in 6 patients of a gestational average of 18 weeks undergoing intraamniotic hypertonic saline infusion for therapeutic abortion. Blood samples were taken before the operation and afterwards at 3-hour intervals for 30 hours. Mean plasma volume increased by 8.9% of the base-line values by 15 hours. The direct correlation found between fluid intake, weight, and plasma volume indicates that unlimited fluid intake may be allowed following saline infusion. Serum electrolytes showed no significant change. Urine sodium and chloride increased at 3 hours, reaching a peak of 60 meg at 27 hours, and returning to base-line values at 36 hours. Urine potassium decreased at 3 hours and remained slightly below base-line values for the remainder of the test period. Disperse variations in the coagulation factor studies might suggest mild diffuse intravascular coagulation, but further research is required.^ieng

Defibrination syndrome after intra-amniotic infusion of hypertonic saline.

PIP: To determine the role of changes in coagulation factors in hermorrhagic complications after intraamniotic infusion of hypertonic saline for therapeutic abortion, 21 women undergoing this operation, ranging 15-38 years in age with an average gestation of 18 weeks, were studied for coagulation factors, fibrinogen survival, and plasma volume. Blood tests were taken before, immediately after, and at 3-hour intervals after infusion of hypertonic saline. Significant changes were found in the following factors: Thrombin clotting time was consistently prolonged from the third hour after infusion. The platelet count dropped significantly from 310,000/cu. mm before infusion to 223,000/cu. mm 18 hours later. Fibrinogen levels dropped significantly from a mean preinfusion level of 393 mg/100 ml to 297 mg/100 ml at 18 hours. Factor VIII levels also fell significantly from 131% of normal at preinfusion to 85% of normal at 6 hours. Factor V levels declined significantly from a preinfusion mean of 104% of normal to 91% at 6 hours, though the rate of decrease varied widely among the patients. Fibrinogan/fibrin, degradation products, negative at preinfusion, appeared in all patients serums. Euglobulin lysis time was not accelerated. Fibrinogen survival studies were conducted in only 5 patients, 4 of whom showed a significant decrease, notably immediately preceding abortion, with a highly significant correlation to the time from infusion. Plasma volume increased significantly with a corresponding decrease in hematocrit. It is concluded that a mild form of diffuse intravascular coagulation develops after the intraamniotic infusion of hypertonic saline, but further research is necessary to pinpoint the cause of serious coagulopathy and hemorrhage.^ieng