Folic Acid Supplementation in Patients with Elevated Homocysteine Levels.

Introduction: Folic acid is the most important dietary determinant of homocysteine (Hcy). Hcy serves as a critical intermediate in methylation reactions. It is created from methionine and either converted back to methionine or transformed into cysteine.

The Dynamic Influence of Olorofim (F901318) on the Cell Morphology and Organization of Living Cells of .

The first characterized antifungal in the orotomide class is olorofim. It targets the de novo pyrimidine biosynthesis pathway by inhibiting dihydroorotate dehydrogenase (DHODH). The pyrimidines uracil, thymine and cytosine are the building blocks of DNA and RNA; thus, inhibition of their synthesis is likely to have multiple effects, including affecting cell cycle regulation and protein synthesis.

Reliable and Easy-To-Use Liquid Chromatography-Tandem Mass Spectrometry Assay for Quantification of Olorofim (F901318), a Novel Antifungal Drug, in Human Plasma and Serum.

A fast and easy-to-use liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the determination and quantification of a novel antifungal drug, olorofim (F901318), a member of the novel class of orotomides, in human plasma and serum was developed and validated. Sample preparation was based on protein precipitation with acetonitrile and subsequent centrifugation. An isotope-labeled analogue of F901318 was employed as an internal standard.

Effect of the Novel Antifungal Drug F901318 (Olorofim) on Growth and Viability of Aspergillus fumigatus.

F901318 (olorofim) is a novel antifungal drug that is highly active against species. Belonging to a new class of antifungals called the orotomides, F901318 targets dihydroorotate dehydrogenase (DHODH) in the pyrimidine biosynthesis pathway. In this study, the antifungal effects of F901318 against were investigated.

F901318 represents a novel class of antifungal drug that inhibits dihydroorotate dehydrogenase.

There is an important medical need for new antifungal agents with novel mechanisms of action to treat the increasing number of patients with life-threatening systemic fungal disease and to overcome the growing problem of resistance to current therapies. F901318, the leading representative of a novel class of drug, the orotomides, is an antifungal drug in clinical development that demonstrates excellent potency against a broad range of dimorphic and filamentous fungi. In vitro susceptibility testing of F901318 against more than 100 strains from the four main pathogenic spp.

A streamlined failure mode and effects analysis.

Purpose: Explore the feasibility and impact of a streamlined failure mode and effects analysis (FMEA) using a structured process that is designed to minimize staff effort.

Methods: FMEA for the external beam process was conducted at an affiliate radiation oncology center that treats approximately 60 patients per day. A structured FMEA process was developed which included clearly defined roles and goals for each phase.

Comparisons of the responses of anterior and posterior human adult male bladder neck smooth muscle to in vitro stimulation.

Objective: To evaluate differing methods of stimulation on strips of human bladder neck smooth muscle and compare muscle taken from the anterior and posterior aspects.

Materials And Methods: Samples of adult human male bladder neck muscle were obtained from patients undergoing open radical prostatectomy. Muscle was taken from either the anterior or posterior (nine and six patients, respectively) aspects of the bladder neck.

Closet addiction in fiction: the search for Christiana Evans.

Mary Ann Evans, who would later become the great nineteenth-century novelist George Eliot, takes up in her first three works of fiction a discussion of the use of alcohol in her own culture. However, it is in "Adam Bede" (1859) that a significant portion of the discussion (the alcoholism of one female character in particular) is so deliberately closeted -- so backgrounded -- that the structure of the text becomes a slippery portrait, not only of the extent to which the culturally pervasive alcoholism of women was persistently denied, but of Eliot's own mother's hidden substance abuse. An important minor character in "Adam Bede," identified by more than one biographer as having a kinship to Eliot's mother Christiana Evans, shows all the signs and symptoms of alcoholism, a phenomenon which even the story's narrator appears to be hiding from the reader.

An evaluation of laparoscopic tissue harvesting for human adult urological smooth muscle physiological experimentation.

Objective: To evaluate the properties of laparoscopically harvested bladder neck and ureteric smooth muscle, compared with tissue obtained at open surgery.

Materials And Methods: Bladder neck was harvested from patients undergoing open (eight) or laparoscopic radical prostatectomy (11). Ureter was obtained from patients undergoing nephrectomy (laparoscopic or open) and cystectomy (open only); obtained openly from 16 and laparoscopically from seven.

Bronchial stenosis: an underreported complication of high-dose external beam radiotherapy for lung cancer?

Purpose: To assess the incidence of clinically significant bronchial stenosis in patients treated with high doses (i.e., >70 Gy) of twice-daily external beam radiation therapy (RT).

Carboplatin/paclitaxel or carboplatin/vinorelbine followed by accelerated hyperfractionated conformal radiation therapy: report of a prospective phase I dose escalation trial from the Carolina Conformal Therapy Consortium.

Purpose: To prospectively determine the maximum-tolerated dose of accelerated hyperfractionated conformal radiotherapy (RT; 1.6 Gy bid) for unresectable locally advanced lung cancer (IIB to IIIA/B) following induction carboplatin/paclitaxel (C/T) or carboplatin/vinorelbine (C/N).

Methods: Induction chemotherapy, C/T or C/N, was followed by escalating doses of conformally-planned RT (73.

Routine use of approximately 60 Gy once-daily thoracic irradiation for patients with limited-stage small-cell lung cancer.

Purpose: To review the outcome of patients with limited-stage small-cell lung cancer receiving daily thoracic irradiation (RT) to approximately 60 Gy.

Methods And Materials: The records of patients treated with RT for limited-stage small-cell lung cancer between 1991 and 1999 at Duke University were retrospectively reviewed. Sixty-five patients were identified who had received continuous course once-daily 1.

New Fe(III)-mediated radical cascade reactions of cyclopropyl silyl ethers.

[reaction: see text] Fe(III)-mediated ring opening of cyclopropyl ethers bearing a phenyl-substituted butenyl side chain leads to the generation of beta-keto radicals that undergo 5-exo cyclization followed by a novel cascade sequence resulting in the formation of tricyclic ethers.

Reversible hypertension in a young female: ureteric obstruction due to endometriosis.

We present the case of a young female who, upon investigation for hypertension, was found to have a ureteric stricture secondary to endometriosis. After excision of the stricture and an end-to-end ureteric anastomosis the patient's blood pressure returned to normal. This case highlights the need to investigate fully hypertension in young people and to consider the possibility of endometriosis in any female who presents with obstructive uropathy.

Randomized controlled trial of a single dermatology nurse consultation in primary care on the quality of life of children with atopic eczema.

Background: Atopic eczema is mostly managed in primary care but there is often insufficient time for patient education; a nurse practitioner could help with this.

Objectives: To evaluate the effects of a single consultation with a primary care nurse on the quality of life (QOL) of children with atopic eczema aged 0.5-16 years and the impact of the disease on their families.

Investigation of upper tracts after resolution of symptoms due to ureteric calculi.

Objective: To determine whether patients with proven ureteric calculi on IVU require repeat IVU after resolution of symptoms and passage of calculus on plain X-ray.

Methodology: IVU reports for a 12-month period were obtained and notes and X-rays of those patients with ureteric calculi were reviewed. Presentation, management and subsequent imaging after resolution of symptoms were determined for each patient.

Can we predict radiation-induced changes in pulmonary function based on the sum of predicted regional dysfunction?

Purpose: To determine whether changes in whole-lung pulmonary function test (PFT) values are related to the sum of predicted radiation therapy (RT)-induced changes in regional lung perfusion.

Patients And Methods: Between 1991 and 1998, 96 patients (61% with lung cancer) who were receiving incidental partial lung irradiation were studied prospectively. The patients were assessed with pre- and post-RT PFTs (forced expiratory volume in one second [FEV1] and diffusion capacity for carbon monoxide [DLCO]) for at least a 6-month follow-up period, and patients were excluded if it was determined that intrathoracic recurrence had an impact on lung function.

Carboplatin/paclitaxel or carboplatin/vinorelbine followed by accelerated hyperfractionated conformal radiation therapy: a preliminary report of a phase I dose escalation trial from the Carolina Conformal Therapy Consortium.

The maximum tolerated dose of conformal radiation therapy delivered at 1.6 Gy bid is being assessed in patients with unresectable stage IIB-IIIB non-small cell lung cancer who have been treated with induction regimens consisting of carboplatin plus paclitaxel or carboplatin plus vinorelbine. Data from the early stages of this parallel phase I study show that the two induction regimens are similar in toxicity and that both induce partial responses in 45% of patients.

73.6 Gy and beyond: hyperfractionated, accelerated radiotherapy for non-small-cell lung cancer.

Purpose: To assess results with twice-daily high-dose radiotherapy (RT) for non-small-cell lung cancer (NSCLC).

Patients And Methods: Between 1991 and 1998, 94 patients with unresectable NSCLC were prescribed > or = 73.6 Gy via accelerated fractionation.

Routine 3D treatment planning: opportunities, challenges, and hazards.

Three-dimensional (3D) treatment planning refers to the use of software and hardware tools to design and implement more accurate and conformal radiation therapy. This is a major advance in oncology that should lead to the reduction of treatment-associated morbidity and facilitate safe dose escalation for many tumor sites. This technology affords the incorporation of physiologic and anatomic information into the treatment planning process, further enhancing our ability to improve the therapeutic ratio.

A new three-dimensional dose distribution reduction scheme for tubular organs.

In tubular structures, spatial aspects of the dose distribution may be important in determining the normal tissue response. Conventional dose-volume-histograms (DVHs) and dose-surface-histograms (DSHs) lack spatial information and may not be adequate to represent the three-dimensional (3D) dose data. A new 3D dose distribution data reduction scheme which preserves its longitudinal and circumferential character is presented.

The role of lung perfusion imaging in predicting the direction of radiation-induced changes in pulmonary function tests.

Background: The aim of this study was to determine whether preradiation (pre-RT) single photon emission computed tomography (SPECT) lung perfusion scans can be used to predict RT-induced changes in pulmonary function tests (PFTs).

Methods: Ninety-four patients irradiated for thoracic tumors had pre-RT SPECT lung perfusion scans. The presence of SPECT hypoperfusion distal to a central mediastinal tumor was qualitatively assessed visually without knowledge of PFT changes.

Can angiotensin-converting enzyme inhibitors protect against symptomatic radiation pneumonitis?

This study was designed to determine whether patients taking angiotensin-converting enzyme (ACE) inhibitors while receiving radiation therapy for lung cancer are protected from developing symptomatic radiation pneumonitis. The records of 213 eligible patients receiving thoracic irradiation for lung cancer with curative intent at Duke University Medical Center from 1994-1997 were reviewed. Of the 213 patients, 26 (12.

The rationale and use of three-dimensional radiation treatment planning for lung cancer.

Treatment of lung cancer with conventional radiation therapy is associated with suboptimal local tumor control and poor long-term survival. Poor local tumor control may result from inaccurate tumor targeting, failure to satisfactorily conform to dose distribution with the target volume, and/or inadequate radiation doses. Three-dimensional treatment planning is a radiotherapy technique that provides more accurate dose targeting via the direct transfer of three-dimensional anatomic information from diagnostic scans into the planning process.

A 7-year audit in a single centre of the results of the modified template retroperitoneal lymph node dissection for testicular teratoma.

Objective: To audit the results of retroperitoneal lymph node dissection (RPLND) after chemotherapy for testicular nonseminomatous germ cell tumour (NSGCT) in a single centre over a 7-year period, using a modified template technique via a midline transabdominal approach.

Patients And Methods: Outcome data were collected prospectively on all patients undergoing RPLND for a residual retroperitoneal mass after chemotherapy for NSGCT between October 1990 and March 1998; 28 patients underwent 32 RPLNDs over this period.

Results: The clinical stage at presentation was stage I in three patients (12%), stage II in 15 (54%), stage III in one (4%) and stage IV in nine (32%).