Diagnostic Yield and Novel Candidate Genes by Exome Sequencing in 152 Consanguineous Families With Neurodevelopmental Disorders.

Importance: Autosomal recessive inherited neurodevelopmental disorders are highly heterogeneous, and many, possibly most, of the disease genes are still unknown.

Objectives: To promote the identification of disease genes through confirmation of previously described genes and presentation of novel candidates and provide an overview of the diagnostic yield of exome sequencing in consanguineous families.

Design, Setting, And Participants: Autozygosity mapping in families and exome sequencing of index patients were performed in 152 consanguineous families (the parents descended from a same ancestor) with at least 1 offspring with intellectual disability (ID).

Concurrent chemoradiotherapy with 5-fluorouracil and mitomycin C for invasive anal carcinoma in human immunodeficiency virus-positive patients receiving highly active antiretroviral therapy.

Purpose: To report the clinical outcomes of chemoradiotherapy (CRT) for anal carcinoma in human immunodeficiency virus (HIV)-infected patients receiving highly active antiretroviral therapy.

Patients And Methods: Between 1997 and 2008, 21 HIV-positive patients who were receiving highly active antiretroviral therapy were treated with CRT (50.4 Gy at 1.

Change in blood test after irradiation with high doses for inactivation of Lassa virus.

In 2006 we had a patient with Lassa fever in the University Hospital of Frankfurt. To insure a short turn-around time from the laboratory, it was necessary to have blood which was not contaminated with viruses. One method of achieving this is by irradiating the blood with high doses of ionising radiation.

Organ preservation treatment using TPF-a pilot study in patients with advanced primary and recurrent cancer of the oral cavity and the maxillary sinus.

Purpose: Induction chemotherapy with Taxotere, cisplatin, and 5-fluororacil (TPF) was mainly used in hypopharyngeal and laryngeal cancer patients for larynx preservation. This study aimed to assess feasibility and toxicity in oral cavity and maxillary sinus cancer patients.

Patients And Methods: Between 2003 and 2008, 21 patients (18 male, three female; mean age 58 years; 15 patients Eastern Cooperative Oncology Group > or =1) suffering from advanced squamous cell cancers of the oral cavity (seven primaries, eight locoregional recurrences) and the maxillary sinus (six patients) were prospectively treated with three cycles of TPF (q3w) and were scheduled to undergo definitive chemoradiation.

Selenium levels during the course of radiotherapy. No influence of irradiation on blood selenium concentration.

Purpose: To evaluate the influence of tumor characteristics and irradiation on blood selenium concentrations and their course during radiotherapy.

Material And Methods: Selenium Levels were determined at various times during radiotherapy (I: beginning, II: mid, III: end, IV: 6 weeks after) by atomic absorption spectrometry in whole blood. The values were correlated with patient-, tumor- and irradiation-related parameters.

Concomitant radiochemotherapy with temozolomide in non-selected patients with newly diagnosed high-grade gliomas.

Background: Malignant gliomas still present a medical challenge, despite decades of continuous extensive research with optimization of surgical techniques, radiotherapy and systemic treatments.

Patients And Methods: From 1999 to 2004, 104 patients with WHO grade III and IVgliomas underwent surgery and received concomitant radiotherapy combined with concomitant oral temozolomide. Patients with progressive disease received sequential 5-day cycles of temozolomide at 28-day intervals.

Retrospective analysis of the superior vena cava syndrome in irradiated cancer patients.

Background: A carcinoma is the underlying cause of superior vena cava syndrome (SVCS) in 95-97% of patients. The aim of our study is to retrospectively analyse the outcome of patients after local radiotherapy compared to literature data.

Patients And Methods: In 35 consecutively registered patients, irradiated because of SVCS, different primary carcinomas (lung, breast, head-and-neck, Non-Hodgkin's lymphoma) were ascertained.

[Organ-preserving treatment in inoperable patients with primary oral and oropharyngeal carcinoma: chances and limitations].

Introduction: The aim of this study was to demonstrate the chances of nonoperative therapy in those patients from an unselected population suffering from primary previously untreated squamous cell carcinomas of the oral cavity and the oropharynx who did not seem to be operable.

Patients And Methods: Following interdisciplinary counseling and extensive individual discussion, 72 (21%) of 340 consecutive patients (1997-2004) did not or did not reasonably seem to be operable; three other patients with stage II disease refused surgery. Of the inoperable patients, 95%suffered from far-advanced stage IV disease, 8% had distant metastases, 14% had synchronous malignancies, 9% were aged over 85 years combined with advanced malignant disease, and nearly 50% were limited in their activity or were even bedridden.

Evaluation of tartrate-resistant acid phosphatase (TRACP) 5b as bone resorption marker in irradiated bone metastases.

Background: The aim of our study was to evaluate if the determination of the active isoform 5b of tartrate-resistant acid phosphatase (TRACP 5b) provides the possibility to monitor the effect of local radiotherapy in bone metastases and if TRACP 5b will predict further osseous progression.

Materials And Methods: In 48 breast cancer patients with bone metastases, patients' characteristics, diagnostic imaging and laboratory investigation, tumor- and therapy-related parameters were registered at the beginning and the end of radiotherapy, as well as 6 and 12 weeks afterwards. TRACP 5b activity was measured using a solid phase immunofixed enzyme activity assay with the monoclonal antibody O1A.

The impact of patient positioning on the adequate coverage of the uterus in the primary irradiation of cervical carcinoma: a prospective analysis using magnetic resonance imaging.

Background And Purpose: The intention of this prospective study is to assess the influence of different patient positionings and the use of belly boards on the coverage of the uterus by standard radiation fields.

Material And Methods: In 21 women with carcinoma of the uterine cervix magnetic resonance imaging (MRI) scans in prone patient position with and without belly board and computed tomography (CT) scans in supine position were analysed after superimposing standard pelvic box fields. Further, all patients underwent a second MRI field control in prone position with belly board to detect intraindividual variations in the uterus position during treatment.

Radiotherapy combined with simultaneous chemotherapy with mitomycin-C and 5-fluorouracil for inoperable head and neck cancer.

The feasibility and effectiveness of a combined chemoradiotherapy treatment modality for locally advanced head and neck cancer was tested in a phase II trial. From March 1995 to June 1998, 35 patients with advanced squamous cell carcinoma of the head and neck were treated with a continuous intravenous infusion of 5-fluorouracil (600 mg m-2 24 h-1 for Days 1 to 5 (120 h)) and mitomycin-C (10 mg m-2 intravenously) on Day 5 during the first week of radiotherapy and on Day 36. 31 patients had stage IV disease; 4 patients had stage III; and 1 patient had stage II.

[Risk of anthropogenic nitrogen and phosphorus entry into the North Sea ecosystem].

The situation of inorganic nutrients (nitrate, ammonia, phosphate, and silicate) in the German Bight was studied during several cruises and found to be very different in early summer of different years. Because of the many permanently changing processes which govern nutrient concentrations, an exact interpretation of the results is difficult. Impact on nutrient situation is given mainly by input from land runoff and rivers, by import from other sea regions, by atmospheric input, by horizontal and vertical mixing of imported substances, by incorporation into living organisms, as well as by the release from biological material.

Baseline characteristics of participants in phase I of the Trials of Hypertension Prevention.

Phase I of the Trials of Hypertension Prevention was designed to test the effectiveness and safety of three life-style (weight loss, sodium restriction, and stress management) and four nutrition supplement (calcium, magnesium, potassium, and fish oil) interventions in reducing diastolic blood pressure (DBP) in persons with a high-normal blood pressure. A total of 2182 persons with a DBP between 80 and 89 mm Hg met the eligibility criteria for participation in phase I and were randomized to one of the active intervention or control treatment groups. Most were white (82%), male (70%), married (76%), nonsmoking (88%), college graduate (53%), full-time employees (91%).

Blood pressure, stroke, and coronary heart disease. Part 2, Short-term reductions in blood pressure: overview of randomised drug trials in their epidemiological context.

There are 14 unconfounded randomised trials of antihypertensive drugs (chiefly diuretics or beta-blockers): total 37,000 individuals, mean treatment duration 5 years, mean diastolic blood pressure (DBP) difference 5-6 mm Hg. In prospective observational studies, a long-term difference of 5-6 mm Hg in usual DBP is associated with about 35-40% less stroke and 20-25% less coronary heart disease (CHD). For those dying in the trials, the DBP difference had persisted only 2-3 years, yet an overview showed that vascular mortality was significantly reduced (2p less than 0.

The community-based randomized trials of pharmacologic treatment of mild-to-moderate hypertension.

The value of pharmacologic treatment of mild-to-moderate hypertension remains controversial despite the availability of data from eight community-based randomized trials including over 34,000 subjects with entry diastolic blood pressures ranging from 85 to 120 mmHg. To obtain more reliable estimates of the effects of treatment, the authors conducted an overview of the data from all of these individual trials, and they found a significant 18% reduction in vascular mortality among subjects allocated to treatment, due chiefly to reductions in fatal stroke and myocardial infarction. Subjects allocated to treatment experienced highly significant reductions of approximately 40% in all stroke (typical odds ratio = 0.

Clinical suspicion of autopsy-proven thrombotic and tumor pulmonary embolism in cancer patients.

Cancer patients are prone to both thrombotic and tumor pulmonary embolism (PE). To identify similarities and differences in their clinical features, we reviewed all autopsies from 1978 to 1982 at Brigham and Women's Hospital and the Dana Farber Cancer Institute. Of 73 patients with solid malignant tumors and PE, 56 had major thrombotic PE and 17 had major tumor embolism to the lungs.

The 2 x 2 factorial design: its application to a randomized trial of aspirin and carotene in U.S. physicians.

The 2 x 2 factorial design calls for randomizing each participant to treatment A or B to address one question and further assignment at random within each group to treatment C or D to examine a second issue, permitting the simultaneous test of two different hypotheses. This design can increase the efficiency of large-scale clinical trials. The Physicians' Health Study, a randomized trial of aspirin and beta-carotene among U.

A randomized trial of aspirin and beta-carotene among U.S. physicians.

The Physicians' Health Study is a randomized, placebo-controlled, double-blind clinical trial underway in the United States to assess the effects of aspirin (325 mg q.o.d.