Reversal of twin-twin transfusion syndrome: frequency, vascular anatomy, associated anomalies and outcome

OBJECTIVE: To determine the frequency of reversal of transfusional gradient and phenotype in a large cohort of prospectively studied cases of twin-twin transfusion syndrome (TTTS) and seek evidence of clinical or placental anastomotic associations. METHODS: Consecutive cases of TTTS seen over an eight-year period with serial documentation of ultrasonic growth, liquor volume and fetal and placental Doppler studies were reviewed. Postnatal injection studies were inspected. RESULTS: Reversal of TTTS occurred in 5 of 96 affected pregnancies (5%). Two of the five cases had underlying aneuploidy or genetic syndrome, higher than the 2% frequency found in cases without reversal of TTTS (p < 0.05). Placental anastomotic configurations provided no consistent explanation for reversal of phenotype. CONCLUSION: This study documents the frequency of reversal of the direction of TTTS, and suggests that it is a heterogeneous condition. Reversal of donor-recipient phenotype may be explained by haemodynamic changes secondary to underlying aneuploidy/genetic syndromes, to the presence of multiple anastomoses in either direction or following laser ablation. This series together with previous case reports argues for a high level of suspicion for underlying aneuploidy, genetic syndrome or structural defects where there is reversal of the donor-recipient phenotype.     

Dysmorphic facial features in aspartylglucosaminuria patients and carriers

The facial photos of 76 aspartylglucosaminuria (AGU) patients, 29 obligate carriers and 78 unrelated controls were evaluated for dysmorphic features to see whether this autosomal recessive lysosomal storage disease includes a dysmorphic facial gestalt in addition to the well-known age-related coarsening of the facies and whether the carrier status of AGU might have an effect on the facial features. A consistent dysmorphic gestalt with hypertelorism, a short and broad nose with round nares, simple often small ears with small or missing lobule and modest folding of helices, thick lips and a square shape of face, was found to be present long before the coarsening begins. Recognition of this pattern of facial features might help in the early diagnosis of AGU. Statistically, puffy eyelids were found to be significantly more frequent in AGU carriers than in controls. These findings support an earlier implication that AGU carrier status might have a slight influence on the phenotype.     

Lung fractional moving blood volume in normally grown and growth restricted foetuses

OBJECTIVE: To examine foetal lung blood perfusion using power Doppler ultrasound (PDU) and to compare fractional moving blood volume (FMBV) and mean pixel intensity (MPI) estimations in the lungs of normally grown (NG) foetuses and foetuses with intrauterine growth restriction (IUGR) and also to correlate foetal lung FMBV and MPI with respiratory complications after birth. METHODS: Lungs of 47 NG and 25 IUGR foetuses after 32 weeks of gestation were examined with PDU. FMBV and MPI were estimated in a defined region in the posterior part of the foetal lung closest to maternal abdominal wall. FMBV and MPI were correlated to foetal weight deviation and gestational age. Perinatal outcome and respiratory complications after birth were recorded in both groups. RESULTS: There were significantly lower FMBV and MPI values in IUGR than in NG foetuses. The overall variation was lower for FMBV than for MPI. There was a slightly higher correlation between FMBV and foetal weight deviation [r = 0.33, 95% confidence intervals (CI) 0.11-0.52] than between MPI and foetal weight deviation (r = 0.26, 95% CI 0.03-0.46). There was no significant correlation between FMBV or MPI and gestational age. No differences between the groups were found in the rate of respiratory complications, and they were not correlated either to the FMBV or MPI. CONCLUSION: FMBV and MPI, estimated from the PDU signals of foetal lung circulation, showed lower values in third-trimester pregnancies complicated by IUGR. The frequency of neonatal respiratory complications was not increased in cases with low pulmonary FMBV and MPI values.     

Is childhood abuse a risk factor for chronic pain in adulthood?

Childhood sexual and physical abuse often are viewed as important factors in the development and persistence of chronic pain syndromes in adulthood. Nevertheless, earlier reviews on this issue have reached conflicting conclusions regarding the veracity of the relationship. In this critical review of existing research on childhood abuse and pain in adulthood, surprisingly mixed evidence is found, with significant effects found most consistently in very large crosssectional studies that rely on self-reported abuse status. The few prospective studies that are available do not support the relationship. When examining the literature from the perspective of epidemiological standards for inferring causation, the authors conclude that the evidence does not demonstrate a causal relationship. It appears that any overall relationship between childhood abuse and pain in adulthood probably is modest in magnitude, if it exists at all. Clinical implications and suggestions for future research directions are discussed.     

A G-quadruplex telomere targeting agent produces p16-associated senescence and chromosomal fusions in human prostate cancer cells

The trisubstituted acridine derivative BRACO-19 has been designed to interact with and stabilize the quadruplex DNA structures that can be formed by folding of the single-stranded repeats at the 3' end of human telomeres. We suggest that the BRACO-19 complex inhibits the catalytic function of telomerase in human cancer cells and also destabilizes the telomerase-telomere capping complex so that cells enter senescence. Here, we present evidence showing that the inhibition of cell growth caused by BRACO-19 in DU145 prostate cancer cells occurs more rapidly than would be expected solely by the inhibition of the catalytic function of telomerase, and that senescence is accompanied by an initial up-regulation of the cyclin-dependent kinase inhibitor p21, with subsequent increases in p16(INK4a) expression. We also show that treatment with BRACO-19 causes extensive end-to-end chromosomal fusions, consistent with telomere uncapping.     

Mortality on the waiting list for coronary artery bypass grafting: incidence and risk factors

BACKGROUND: Insufficient capacity for coronary artery bypass grafting results in waiting times before operation, prioritization of patients and, ultimately, death on the waiting list. We aimed to calculate waiting list mortality and to identify risk factors for death on the waiting list. METHODS: The study included 5,864 consecutive patients accepted for elective coronary artery bypass grafting (78% male; mean age, 66 +/- 9 years). The patients were categorized at acceptance into three priority groups: imperative (39%), urgent (36%), or routine (25%). Waiting list mortality was calculated and compared between groups, and risk factors were identified by Poisson regression. RESULTS: Median waiting time for the whole population was 55 days. Seventy-seven patients (1.3%) died, corresponding to a mortality rate of 5.8 deaths per 100 patient-years. The mortality rate per 100 patient-years was highest for those in the imperative group, 15.1 deaths, compared with 5.3 deaths in the urgent group and 3.2 in the routine group (p < 0.001). Independent risk factors were male sex (p = 0.032), Cleveland Clinic risk score (p = 0.005), impaired left ventricular ejection fraction (p = 0.007), unstable angina pectoris (p = 0.001), concomitant aortic valve disease (p = 0.002), priority group (p < 0.001), and time after acceptance (p = 0.019). The mortality risk increased with time after acceptance by 11% a month. CONCLUSIONS: Long waiting lists for coronary artery bypass grafting are associated with considerable mortality. The risk of death increases significantly with waiting time. Sex, unstable angina, perioperative risk, impaired left ventricular function, and concomitant aortic valve disease are independent risk factors and should be considered at triage.     

Differential Bone Turnover in an Angulated Fracture Model in the Rat

We have developed a simple rat model of angulated tibial fracture which elicits substantial differences in bone formation and resorption within the same bone. In 35 rats the right mid-tibia was manually fractured and fixed with an intramedullary 17-gauge cannula needle. Twenty tibias were fixed in anterior angulation (27 ± 5°) and 15 in posterior angulation (31 ± 5°). Serial X-rays were taken over a 12-week period. All fractures healed completely within five weeks. In both groups, bone thickness was already significantly greater on the concave side than on the convex side at week 3 and remained so until the end of the experiment. The thickness on the convex side decreased dramatically within 3 to 5 weeks and gradually thereafter. For morphological analysis of bone mineralization, 3 rats from each group were given calcein and alizarin red injected at different time points up to 14 weeks. Maximum new bone formation was noted within the first 3 weeks. Over the ensuing weeks, new bone formation remained intense on the concave side, but it was virtually absent on the convex side. These results show that angulated fracture deformity reproducibly exhibits differential bone turnover, which can be exploited in research on local regulatory factors. To exemplify the utility of the model, an immunohistochemical study on two local markers was done. Callus tissue of five rats in the anterior angulation group at week 3 post-fracture was stained for the cytokine IL-1, a stimulator of bone resorption, and the neuropeptide CGRP, an inhibitor of resorption, showing clear differences in positive staining between the concave and convex sides. Our in-vivo model offers a means of analyzing morphologically and quantitatively the differential expression and action of factors involved in local bone turnover.     

The potential value of (Myo)fibroblastic stromal reaction in the diagnosis of prostatic adenocarcinoma

BACKGROUND: Reactive stromal changes that occur in different human cancers probably are involved in local tumor spreading. The aim of this study was to analyze changes of the stroma in prostatic carcinoma and to establish their possible diagnostic significance. METHODS: For the definition of reactive stroma in prostate cancer Mallory trichrome method and immunohistochemical analysis of vimentin, alpha-smooth muscle actin, and desmin were performed. RESULTS: Compared with adjacent peritumoral tissue and stroma in benign prostatic hyperplasia, reactive stroma in prostate cancer showed increased vimentin expression, and decreased desmin expression (P < 0.05). Mallory method also showed more pronounced desmoplastic reaction in stroma of prostatic adenocarcinoma (P < 0.05). CONCLUSIONS: Our study indicates that a reactive stroma, which occurs in prostatic carcinoma, could be clearly shown by Mallory method and confirmed by immunohistochemistry. We suggest that Mallory trichrome method may be used as a helpful additional diagnostic tool in the diagnosis of suspicious cases of prostatic adenocarcinoma.