The contribution of activated factor XIII to fibrinolytic resistance in experimental pulmonary embolism

BACKGROUND: The resistance of thrombi to fibrinolysis induced by plasminogen activators remains a major impediment to the successful treatment of thrombotic diseases. This study examines the contribution of activated factor XIII (factor XIIIa) to fibrinolytic resistance in experimental pulmonary embolism. METHODS AND RESULTS: The fibrinolytic effects of specific inhibitors of factor XIIIa-mediated fibrin-fibrin cross-linking and alpha2-antiplasmin-fibrin cross-linking were measured in anesthetized ferrets with pulmonary emboli. Five experimental groups were treated with heparin (100 U/kg) and/or tissue plasminogen activator (TPA, 1 mg/kg) and the percent (mean+/-SD) lysis of emboli was determined: (1) control, normal factor XIIIa activity (14.1+/-4. 8% lysis); (2) inhibited factor XIIIa activity (42.7+/-7.4%); (3) normal factor XIIIa activity+TPA (32.3+/-7.7%); (4) inhibited factor XIIIa activity+TPA (76.0+/-11.9%); and (5) inhibited alpha2-antiplasmin-fibrin cross-linking+TPA (54.7+/-3.9%). Inhibition of factor XIIIa activity increased endogenous lysis markedly (group 1 versus 2; P<0.0001), to a level comparable to that achieved with TPA (group 2 versus 3; P<0.05). Among groups receiving TPA, selective inhibition of factor XIII-mediated alpha2-antiplasmin-fibrin cross-linking enhanced lysis (group 3 versus 5; P<0.0005). Complete inhibition of factor XIIIa also amplified lysis (group 3 versus 4; P<0.0001) and had greater effects than inhibition of alpha2-antiplasmin cross-linking alone (group 4 versus 5; P<0.0005). No significant fibrinogen degradation occurred in any group. CONCLUSIONS: Factor XIIIa-mediated fibrin-fibrin and alpha2-antiplasmin-fibrin cross-linking both caused experimental pulmonary emboli to resist endogenous and TPA-induced fibrinolysis. This suggests that factor XIIIa may play a critical role in regulating fibrinolysis in human thrombosis.     

Activated natural killer cells and interleukin-2 promote granulocytic and megakaryocytic reconstitution after syngeneic bone marrow transplantation in mice

Purified populations of natural killer (NK) cells were obtained from mice with severe combined immune deficiency (SCID). SCID spleen cells were cultured and activated with recombinant human interleukin-2 (rhIL- 2) in vitro. The activated NK cells were then transferred with syngeneic BALB/c bone marrow cells (BMC) and rhIL-2 into lethally irradiated syngeneic recipients to determine their effect on long-term hematopoietic reconstitution. On analysis, the transfer of rhIL-2- activated NK cells along with BMC resulted in significant increases in splenic and BM hematopoietic progenitor cells when compared with those for mice not receiving NK cells. Histologic and flow cytometric analysis showed a marked increase in granulocytic and megakaryocytic lineage cells present in the spleens of the mice receiving activated NK cells. Analysis of the peripheral blood indicated that the transfer of activated NK cells with BMC also significantly improved platelet and total white blood cell counts, with increases in segmented neutrophils. Erythroid recovery was not affected. Finally, lethally irradiated mice receiving activated NK cells and rhIL-2 along with limiting numbers of syngeneic BMC showed a marked increase in survival rate. These results show that the use of populations enriched for activated NK cells after syngeneic BM transplantation (BMT) has a profound enhancing effect on engraftment primarily affecting megakaryocytic and granulocytic cell reconstitution. Therefore, the transfer of activated NK cells and rhIL- 2 may be of clinical use to promote hematopoietic reconstitution after BMT.     

Perianal anatomy in non-abused preschool children

The purpose of this study was to describe the normal variation in perianal anatomy in preschool children, selected for non-abuse, and to compare the findings in two examination positions. A letter of invitation was sent to 3773 children, after which 305 children (103 boys and 202 girls) were recruited. Inclusion in the study was based on self-selection, whereby parents who did not suspect any occurrence of sexual abuse of their child gave informed consent to participate. The mean age of the children was 5.63 y (range: 5.13-6.75). An anal examination was performed in the left lateral position (LLP) and the prone knee-chest position (KCP), for approximately 30 s each. A colposcope and a camera were used. All data were systematically analysed for gender differences, and a paired sample test was used to compare findings in LLP and KCP. Venous congestion in LLP and external anal dilatation in both positions were significantly more common in girls, while midline depressions and smooth areas (both positions) were significantly more common in boys. External and total anal dilatation, midline smooth areas and depressions and the occurrence of a prominent anal verge were significantly more common in the KCP. The finding of total anal dilatation was rare. CONCLUSION: We observed several gender and position differences in perianal anatomy, and most of these findings seem to be related to structure and tone in the anal muscles.     

ENDOMETRIOMA OF THE LIVER

Hepatic endometriosis is extremely rare. The diagnosis is often missed and treatment is delayed. A 37-year-old woman was referred to the gynaecology department with vague abdominal pains. She had a past history of pelvic endometriosis and hysterectomy with bilateral salpingo-oophorectomy. Further investigations in due course confirmed it to be endometriosis of the liver. She was eventually referred to the hepatobiliary unit, almost three years after her first presentation, where she was operated on with good results.     

Increased number of substitutions in the D-loop of mitochondrial DNA in the sudden infant death syndrome

The purpose of the present study was to investigate substitutions in the D-loop of mitochondrial DNA (mtDNA) in sudden infant death syndrome (SIDS) and controls, since several observations indicate the involvement of mtDNA mutations in SIDS. These include elevated levels of vitreous humour hypoxanthine in SIDS victims, familial clustering without mendelian traits, and observations of increased sleepiness and a lower activity score in infants who later succumbed to SIDS. Eighty-two cases of SIDS and 133 controls were investigated and the D-loop sequences were recorded in the base-pair range 16 055-16 500 in the mtDNA sequence. The sequencing was carried out using the Applied Biosystems Sequenase dye terminator method and a ABD373A sequencer. The recorded D-loop sequences were compared with the Cambridge sequence and differences were recorded as substitutions. The SIDS cases had a tendency towards a higher substitution rate in the D-loop than the controls ( p = 0.088). This observation makes it interesting to search for deleterious mutations in other locations in the mtDNA.     

Evaluation of scleral incisions and their effects on corneal curvature in manual small-incision cataract surgery

Purpose:Incisions in cataract surgery can be modified in various ways in terms of size, shape, and axis to reduce or tailor astigmatism. This study was conducted to examine the effect of site (superior vs, temporal) and shape (frown vs. V-shaped, chevron) of scleral incisions for cataract surgery on corneal curvature.Methods:The prospective study was carried out on 200 consecutive patients with senile cataract and who were planned for surgery at a tertiary eye hospital in north India. The placement of the incision was decided by the steeper corneal meridian—whether superior or temporal—and then patients of these two groups were randomized for frown and V-shaped incision; in this way, four groups of 50 patients each were formed. Follow-up was done on day 1, at 2 weeks, 4 weeks, 8 weeks, and 12 weeks. At each follow-up, post-operative keratometry with routine postoperative examination was done. The results were statistically analyzed by using student’s t-test, Chi-squared test, and the Pearson correlation coefficient.Results:In all the four groups, the difference of preoperative astigmatism and surgically-induced astigmatism was statistically highly significant. The analysis of uncorrected visual acuity (UCVA) was statistically significant (P < 0.05) on postoperative day 1 and at 2, 4, and 12 postoperative weeks; it was statistically insignificant (P > 0.05) at postoperative week 8.Conclusion:Temporal incisions result in lesser postoperative surgically induced astigmatism (SIA) than superior incisions. Chevron incisions result in minimal change in corneal curvature. This effect can be utilized to tailor the postoperative astigmatism.     

Anxiety and depression levels of healthcare workers during Covid-19 pandemic

BackgroundCoronavirus disease 2019 (covid-19), which causes a pandemic in the world, has started to appear in turkey since march 2020. Healthcare workers are at the top of the groups most at risk for covid-19 infection, which can have a negative impact on psychological state.ObjectivesIt was aimed to evaluate anxiety and depression levels among healthcare workers.Methodsthis cross-sectional study performed via an online survey in april 2020. Participants answered questions about sociodemographic features, personal views and experiences about covid-19 and the hospital anxiety and depression scale (hads).ResultsA total of 300 healthcare workers,193 men and 107 women, participated in the survey. According to hads, 44.6% of participants scored above anxiety and 68.2% scored above depression cut-off points. Being younger than 50 and taking care of covid-19 patients in hospitals were independently associated with anxiety risk. Female gender, young age (less than 50) and having comorbidity were independent risk factors for depression.ConclusionHealthcare workers were at high risk of anxiety and depression during covid-19 outbreak. For this reason, psychological support should be given, especially to the group with high risk.