Radiation sensitivity of the gastrula-stage embryo: Chromosome aberrations and mutation induction in lacZ transgenic mice: The roles of DNA double-strand break repair systems.

At the gastrula phase of development, just after the onset of implantation, the embryo proper is characterized by extremely rapid cell proliferation. The importance of DNA repair is illustrated by embryonic lethality at this stage after ablation of the genes involved. Insight into mutation induction is called for by the fact that women often do not realize they are pregnant, shortly after implantation, a circumstance which may have important consequences when women are subjected to medical imaging using ionizing radiation.

Effect of levothyroxine on live birth rate in euthyroid women with recurrent miscarriage and TPO antibodies (T4-LIFE study).

Background: Thyroid peroxidase antibodies (TPO-Ab) in euthyroid women are associated with recurrent miscarriage (RM) and other pregnancy complications such as preterm birth. It is unclear if treatment with levothyroxine improves pregnancy outcome.

Aim: The aim of this study is to determine the effect of levothyroxine administration on live birth rate in euthyroid TPO-Ab positive women with recurrent miscarriage.

Antithrombotic strategy after bioprosthetic aortic valve replacement in patients in sinus rhythm: evaluation of guideline implementation.

Objectives: After elective aortic valve replacement, patients are at risk of developing valve thrombosis and systemic arterial thromboembolism. Current guidelines recommend antithrombotic therapy with aspirin or vitamin K antagonists (VKAs) during the first 3 months after the procedure, but have level 2 or 3 evidence. As a consequence, the most appropriate antithrombotic therapy is still a matter of debate.

Associations between insulin action and integrity of brain microstructure differ with familial longevity and with age.

Impaired glucose metabolism and type 2 diabetes have been associated with cognitive decline, dementia, and with structural and functional brain features. However, it is unclear whether these associations differ in individuals that differ in familial longevity or age. Here, we investigated the association between parameters of glucose metabolism and microstructural brain integrity in offspring of long-lived families ("offspring") and controls; and age categories thereof.

Homocysteinemia After Hypertensive Pregnancy Disorders at Term.

Background: Results from a number of long-term follow-up studies have suggested that hypertensive disorders in pregnancy are associated with increased risk of cardiovascular disease later in life. More recently, this putative relationship has been substantiated with findings of elevated cardiovascular risk factors, such as lipid profiles and glucose, in women with a history of hypertensive pregnancy disorders. Homocysteine is a sensitive indicator of increased risk but data on homocysteine levels in women with a history of hypertensive pregnancy disorders are inconsistent.

Humoral responses to HIVconsv induced by heterologous vaccine modalities in rhesus macaques.

Vaccines delivering T cell immunogen HIVconsv vectored by plasmid DNA, non-replicating simian adenovirus and non-replicating modified vaccinia virus Ankara (MVA) are under clinical evaluation in phase I/IIa trials in UK, Europe, and Africa. While these vaccines aim to induce effector T cell responses specific for HIV-1, we here characterized the humoral responses induced by HIVconsv administration to macaques using six different vaccine modalities: plasmid DNA, human adenovirus serotype 5, simian adenovirus serotype 63, MVA, Semliki Forest virus replicons, and adjuvanted overlapping synthetic long peptides (SLP). We found that only the SLP formulation, but none of the genetic vaccine platforms induced antibodies recognizing linear HIVconsv epitopes, median 32/46 SLP.

Abnormal cortical synaptic transmission in CaV2.1 knockin mice with the S218L missense mutation which causes a severe familial hemiplegic migraine syndrome in humans.

Familial hemiplegic migraine type 1 (FHM1) is caused by gain-of-function mutations in CaV2.1 (P/Q-type) Ca(2+) channels. Knockin (KI) mice carrying the FHM1 R192Q missense mutation show enhanced cortical excitatory synaptic transmission at pyramidal cell synapses but unaltered cortical inhibitory neurotransmission at fast-spiking interneuron synapses.

The diagnostic value of routine antenatal ultrasound in screening for congenital uropathies.

Background: Antenatal hydronephrosis (ANH) is characteristic for congenital obstructive abnormalities of the urinary tract (COAUT). COAUT is the most common cause of urinary tract infections (UTI's) in newborns. The prognosis of mild to moderate ANH is unclear.

Cognate CD4 T-cell licensing of dendritic cells heralds anti-cytomegalovirus CD8 T-cell immunity after human allogeneic umbilical cord blood transplantation.

Unlabelled: Reactivation of human cytomegalovirus (CMV) is hazardous to patients undergoing allogeneic cord blood transplantation (CBT), lowering survival rates by approximately 25%. While antiviral treatment ameliorates viremia, complete viral control requires CD8+ T-cell-driven immunity. Mouse studies suggest that cognate antigen-specific CD4+ T-cell licensing of dendritic cells (DCs) is required to generate effective CD8+ T-cell responses.

ALS as a distal axonopathy: molecular mechanisms affecting neuromuscular junction stability in the presymptomatic stages of the disease.

Amyotrophic Lateral Sclerosis (ALS) is being redefined as a distal axonopathy, in that many molecular changes influencing motor neuron degeneration occur at the neuromuscular junction (NMJ) at very early stages of the disease prior to symptom onset. A huge variety of genetic and environmental causes have been associated with ALS, and interestingly, although the cause of the disease can differ, both sporadic and familial forms of ALS show a remarkable similarity in terms of disease progression and clinical manifestation. The NMJ is a highly specialized synapse, allowing for controlled signaling between muscle and nerve necessary for skeletal muscle function.

Sensitivity of hematological malignancies to graft-versus-host effects: an EBMT megafile analysis.

After allogeneic stem cell transplantation, graft-versus-host disease (GvHD) occurs through recognition of histocompatibility mismatches by donor T lymphocytes. The same mechanism operates in eliminating malignant cells (the graft-versus-tumor or GvT effect). We hypothesized that comparing the correlation between GvHD and relapse might provide a surrogate marker for the susceptibility of diseases to allo-immune effects.

Epidemiology and trends in severe burns in the Netherlands.

Introduction: The aim of this study was to characterize the epidemiology of severe burns in the Netherlands, including trends in burn centre admissions, non burn centre admissions and differences by age.

Methods: Patients with burn-related primary admission in a Dutch centre from 1995 to 2011 were included. Nationwide prospectively collected data were used from three separate historical databases and the uniform Dutch Burn Repository R3 (2009 onwards).

Emotional reactions of peers influence decisions about fairness in adolescence.

During adolescence, peers take on increasing importance, while social skills are still developing. However, how emotions of peers influence social decisions during that age period is insufficiently known. We therefore examined the effects of three different emotional responses (anger, disappointment, happiness) on decisions about fairness in a sample of 156 adolescents aged 12-17 years.

Brachytherapy after external beam radiotherapy and limited surgery preserves bladders for patients with solitary pT1-pT3 bladder tumors.

Background: Several French, Belgian and Dutch radiation oncologists have reported good results with the combination of limited surgery after external beam radiotherapy (EBRT) followed by brachytherapy in early-stage muscle-invasive bladder cancer.

Patients And Methods: Data from 12 of 13 departments which are using this approach have been collected retrospectively, in a multicenter database, resulting in 1040 patients: 811 males and 229 females with a median age of 66 years, range 28-92 years. Results were analyzed according to tumor stage and diameter, histology grade, age and brachytherapy technique, continuous low-dose rate (CLDR) and pulsed dose rate (PDR).

Is surveillance of the small bowel indicated for Lynch syndrome families?

Background: Small bowel cancer (SBC) is one of the tumours associated with Lynch syndrome (LS). To advise on screening for this tumour it is paramount to be informed about the lifetime risk. The aim of this study was to calculate the lifetime risk of SBC in LS and to identify possible risk factors.

A retrospective analysis of five intra-ocular lenses and the predictive value of six different intra-ocular lens power calculation formulas.

Purpose: To evaluate the refractive and visual outcome after implantation of five different lenses and to evaluate the accuracy of six different intra-ocular lens (IOL) power formulas.

Setting: Department of Ophthalmology, University Medical Centre Rotterdam, The Netherlands.

Methods: In total, 288 eyes had cataract surgery with implantation of a polymethylmethacrylate lens (Centra55B) or a foldable silicone lens (AMO SI40, Staar AA, Silens 5, Pliolens).

Diagnostic methods in pulmonary embolism.

Diagnosing pulmonary embolism (PE) is challenging since clinical signs and symptoms are non-specific. The diagnostic tests available for demonstrating PE all have their drawbacks and are often costly and consume considerable amounts of resources. Simple tools that have become available in the last several years include clinical prediction rules and D-dimer testing.

The role of helical CT in the diagnosis of pulmonary embolism.

Diagnosing pulmonary embolism is problematic since clinical signs and symptoms of PE are aspecific. Diagnostic algorithms have been developed to rationalize the use of imaging tests in patients with a clinical suspicion of PE. An algorithm based on helical CT has gained widespread interest due to the availability of helical CT.

Decision analysis in the surgical treatment of colorectal cancer due to a mismatch repair gene defect.

Background: In view of the high risk of developing a new primary colorectal carcinoma (CRC), subtotal colectomy rather than segmental resection or hemicolectomy is the preferred treatment in hereditary non-polyposis colorectal cancer (HNPCC) patients. Subtotal colectomy however implies a substantial decrease in quality of life. To date, colonoscopic surveillance has been shown to reduce CRC occurrence.

Surgical treatment for recurrent gastro-oesophageal reflux disease after failed antireflux surgery.

Background: Recurrent or persistent symptoms occur in 10-15 per cent of patients after antireflux surgery. Failure of surgery is not uniform in its presentation. The cause of failure is not easily detected and even harder to treat.

Cystic fibrosis: MR imaging of the pancreas.

The appearance of the pancreas in 17 adult patients with cystic fibrosis was evaluated with magnetic resonance (MR) imaging. The pancreas was abnormal in 15 patients. Three patterns were observed: (a) lobulated enlarged pancreas with complete replacement by fatty tissue (n = 9), (b) small atrophic pancreas with partial replacement by fat tissue (n = 5), and (c) diffuse atrophy of the pancreas without fatty replacement (n = 1).

Systemic cancer and the FAMMM syndrome.

The FAMMM syndrome consists of the familial occurrence of cutaneous malignant melanoma and atypical nevi (dysplastic nevi), and is inherited as an autosomal dominant trait. Conflicting results have been reported on the question of whether the syndrome includes increased susceptibility to non-melanoma cancers. We have studied cancer of all anatomic sites and histologies in nine FAMMM families which were ascertained in a pigmented lesions clinic in the Netherlands.

Abnormalities of the uterus and cervix after diethylstilbestrol exposure: correlation of findings on MR and hysterosalpingography.

We determined the value of MR for detecting abnormalities of the uterus caused by in utero exposure to diethylstilbestrol in patients in whom such abnormalities were evident on hysterosalpingography. Of 200 women with a history of diethylstilbestrol exposure in utero, 12 had undergone hysterosalpingography as part of an infertility workup. Five of these volunteered to undergo MR imaging of the pelvis.

CT and MR imaging of advanced Zollinger-Ellison syndrome.

The CT and magnetic resonance (MR) findings in 13 patients with advanced Zollinger-Ellison syndrome are described. In eight patients (62%) one or more primary tumors were found with both methods. All patients with proven liver metastases (n = 7) were identified by MR.