Ages and Stages Questionnaire used to measure cognitive deficit in children born extremely preterm

AIM: To validate the Ages and Stages Questionnaire (ASQ) and to measure average cognitive deficit in children born extremely preterm. METHODS: Parents of 30 term children aged 36-42 mo completed the ASQ and the children underwent the Wechsler Preschool and Primary Scales of Intelligence--Revised. In a second study, the ASQ was obtained in 22 children born extremely preterm and 19 term children at the age of 35-44 mo. RESULTS: The overall ASQ score correlated significantly with IQ (p=0.007). The children born extremely preterm had an ASQ score of -1.06 SD below the score of the term children (p=0.048). CONCLUSION: The ASQ identified a developmental deficit of the expected magnitude.     

Geographic and temporal variations in cancer of the corpus uteri: incidence and mortality in pre- and postmenopausal women in Europe

Corpus uteri cancer is the fourth most common neoplasm in women in Europe and the tenth most common cause of cancer death. We examined geographic and temporal variations in corpus uteri cancer incidence and mortality rates in the age groups 25-49 and 50-74 in 22 European countries. The disease is considerably less common in premenopausal women, with incidence and mortality rates decreasing throughout Europe and mortality declines more marked in western and southern European countries. Incidence rates among postmenopausal women are highest in the Czech Republic, Slovakia, Sweden and Slovenia and lowest in France and the United Kingdom. Increasing incidence trends in this age group are observed in the Nordic countries (except Denmark) and in the United Kingdom. Some increases are also seen in eastern (Slovakia) and southern Europe (Spain and Slovenia), while relatively stable or modestly decreasing trends are observed in Italy and most western European countries. Postmenopausal mortality rates are systematically higher in eastern Europe, with death rates in the Ukraine, Latvia, Czech Republic, Russia and Belarus 2-3 times those seen in western Europe. Declining mortality trends are seen in most populations, though in certain Eastern European countries, the declines began rather recently, during the 1980s. In Belarus and Russia, recent postmenopausal death rates are stable or increasing. The rates are adjusted for misclassification of uterine cancer deaths but remain unadjusted for hysterectomy, and where there is an apparent levelling off of incidence or mortality rates recently, rising prevalence of hysterectomy cannot be discounted as an explanation. However, the trends by age group can be viewed in light of several established risk factors for endometrial cancer that are highly prevalent and most likely changing with time. These are discussed, as are the prospects for preventing the disease.     

Diffuse large B-cell lymphoma with combined TP53 mutation and MIR34A methylation: Another “double hit” lymphoma with very poor outcome?

MiR34A, B and C have been implicated in lymphomagenesis, but information on their role in normal CD19+ B-cells (PBL-B) and de novo diffuse large B-cell lymphoma (DLBCL) is limited.We show that in normal and activated B-cells miR34A-5p plays a dominant role compared to other miR34 family members. Only miR34A-5p is expressed in PBL-B, and significantly induced in activated B-cells and reactive lymph nodes. In PBL-B, the MIR34A and MIR34B/C promoters are unmethylated, but the latter shows enrichment for the H3K4me3/H3K27me3 silencing mark.Nine de novo DLBCL cases (n=150) carry both TP53 mutation and MIR34A methylation (“double hit”) and these patients have an exceedingly poor prognosis with a median survival of 9.4 months (P<0.0001), while neither TP53 mutation, MIR34A or MIR34B/C promoter methylation alone (“single hit”) influence on survival. The TP53/MIR34A “double-hit” is an independent negative prognostic factor for survival (P=0.0002). In 2 DLBCL-cell lines with both TP53 mutation and promoter methylation of MIR34A, miR34A-5p is upregulated by 5-aza-2''deoxycytidine. Thus, the TP53/MIR34A “double hit” characterizes a very aggressive subgroup of DLBCL, which may be treatable with epigenetic therapy prior to or in combination with conventional immunochemotherapy.     

Mismatch repair defective breast cancer in the hereditary nonpolyposis colorectal cancer syndrome

Whether or not breast cancer can be a feature of the hereditary nonpolyposis colorectal cancer (HNPCC) syndrome has been debated. In order to clarify if defective mismatch repair (MMR) may indeed play a role in breast cancer, we used the Danish HNPCC register to identify all breast cancers that occurred in MMR gene mutation carriers. In total, 20 female mutation carriers were diagnosed with breast cancer at mean 50 years of age. These tumors were predominantly ductal carcinomas with extensive lymphocytic reactions in 8/14 evaluated tumors. MMR protein immunostaining showed loss of expression of MLH1, MSH2 or MSH6 corresponding to the mutations identified in 7 of the 16 cases investigated, and these tumors were diagnosed at mean 50 (33–66) years of age. The demonstration of defective MMR in a substantial proportion of the breast cancers studied links yet another tumor type to HNPCC. Though the low number do not motivate surveillance, our observation supports a role for defective MMR in breast cancer progression in HNPCC, presumably through accelerated accumulation of mutations in breast cancer-associated genes.     

Influence of histamine and pentobarbitone on plasma and CSF vasopressin levels of hypophysectomized rats

Histamine increased vasopressin levels, as measured by radioimmunoassay (RIA), in both cerebrospinal fluid (CSF) and plasma of hypophysectomized rats, while histamine enhanced plasma but not CSF levels of vasopressin in sham operated rats. Pentobarbitone increased CSF vasopressin levels in hypophysectomized rats and in sham operated animals. The present data demonstrate that the histamine induced elevation of vasopressin levels in the blood is only temporarily disturbed after hypophysectomy, while the effect of histamine on CSF vasopressin levels of hypophysectomized rats is of a more permanent nature.     

Redefining the Koizumi model of mouse cerebral ischemia: A comparative longitudinal study of cerebral and retinal ischemia in the Koizumi and Longa middle cerebral artery occlusion models

Cerebral and retinal ischemia share similar pathogenesis and epidemiology, each carrying both acute and prolonged risk of the other and often co-occurring. The most used preclinical stroke models, the Koizumi and Longa middle cerebral artery occlusion (MCAO) methods, have reported retinal damage with great variability, leaving the disruption of retinal blood supply via MCAO poorly investigated, even providing conflicting assumptions on the origin of the ophthalmic artery in rodents. The aim of our study was to use longitudinal in vivo magnetic resonance assessment of cerebral and retinal vascular perfusion after the ischemic injury to clarify whether and how the Koizumi and Longa methods induce retinal ischemia and how they differ in terms of cerebral and retinal lesion evolution. We provided anatomical evidence of the origin of the ophthalmic artery in mice from the pterygopalatine artery. Following the Koizumi surgery, retinal responses to ischemia overlapped with those in the brain, resulting in permanent damage. In contrast, the Longa method produced only extensive cerebral lesions, with greater tissue loss than in the Koizumi method. Additionally, our data suggests the Koizumi method should be redefined as a model of ischemia with chronic hypoperfusion rather than of ischemia and reperfusion.     

Effect of nitrofurantoin and methenamine hippurate prophylaxis on bacteria and yeasts in the urine of patients with an indwelling catheter

Nitrofurantoin or methenamine hippurate was given prophylactically to elderly patients without urinary tract infection at the beginning of long-term catheterization (mean 81 days), but it only delayed the appearance of bacteriuria. Escherichia coli was most frequently the first species to appear (≥10⁴/ml) in the urine of 40 patients given methenamine hippurate as well as in the control group (41 patients), whereas in 42 patients treated with nitrofurantoin more resistant species, such as Proteus mirabilis, Providencia spp. and Pseudomonas aeruginosa most often appeared first. Weekly tests made during the course of catheterization showed that E. coli disappeared from the nitrofurantoin-treated patients, while pseudomonas increased in this group and providencia in the control group. Pseudomonas was isolated more frequently in the nitrofurantoin than other groups. With the exception of klebsiellae, the bacterial strains isolated from the nitrofurantoin group were as sensitive to various antibiotics as were those from other groups. Significantly more samples with growth of yeasts (≥10⁴/ml) were obtained from nitrofurantoin treated than from methenamine hippurate treated patients. Candida albicans was the species of yeasts most often isolated.