Inhibition of mitochondrial respiration by the anticancer agent 2-methoxyestradiol.

2-Methoxyestradiol (2ME2), a naturally occurring metabolite of estradiol, is known to have antiproliferative, antiangiogenic, and proapoptotic activity. Mechanistically, 2ME2 has been shown to downregulate hypoxia-inducible factor 1alpha (HIF1alpha) and to induce apoptosis in tumour cells by generating reactive oxygen species (ROS). In this study we report that 2ME2 inhibits mitochondrial respiration in both intact cells and submitochondrial particles, and that this effect is due to inhibition of complex I of the mitochondrial electron transport chain (ETC).

Does the presence of a tracheal bronchus affect the margin of safety of double-lumen tube placement?

During double-lumen tube (DLT) placement, the anesthesiologist must be mindful of the margin of safety. We determined how this margin is affected by the presence of a tracheal bronchus by elucidating the mathematical relationship between some relevant physical dimensions of the trachea, bronchi, and DLT. Our results suggest that a tracheal bronchus only rarely affects the intrinsic margin of safety of DLT placement.

Time course and substance P effects on the vascular and morphological changes in adjuvant-induced monoarthritic rats.

The aim of this study is to characterize the time course of the vascular and morphological changes in arthritic rat knee joints induced by Freund's complete adjuvant (FCA), and to investigate the effects of substance P on these changes. Single unilateral intra-articular injections of 0.1 ml FCA produced swelling of the ipsilateral knees for 4 weeks, blood vessel permeability was increased for 1 week, but blood flow was unaffected except for minor bilateral increases on day 28.

Acute rejection after renal transplantation is reduced by approximately 50% by prior therapeutic blood transfusions, even in tacrolimus-treated patients.

Background: The authors investigated the relationship between therapeutic blood transfusion before renal transplantation and rejection rates in cyclosporine- and tacrolimus-treated patients.

Methods: In one center, 265 consecutive recipients were studied. Protocol induction was with azathioprine, prednisolone, and cyclosporine or tacrolimus; 37% had biopsy-proven acute rejection in the first 6 months and 46% had received zero to two units of blood before transplantation.

Hyponatraemia and hyperkalaemia are more frequent in renal transplant recipients treated with tacrolimus than with cyclosporin. Further evidence for differences between cyclosporin and tacrolimus nephrotoxicities.

Background: This study was designed to examine the hypothesis that the nephrotoxicities caused by cyclosporin and tacrolimus might differ in respect of sodium and potassium handling.

Methods: 125 patients were studied retrospectively for the first 90 days after renal transplantation. Eighty were treated initially with cyclosporin and 45 with tacrolimus.

Redistribution of intracellular oxygen in hypoxia by nitric oxide: effect on HIF1alpha.

Cells exposed to low oxygen concentrations respond by initiating defense mechanisms, including the stabilization of hypoxia-inducible factor (HIF) 1alpha, a transcription factor that upregulates genes such as those involved in glycolysis and angiogenesis. Nitric oxide and other inhibitors of mitochondrial respiration prevent the stabilization of HIF1alpha during hypoxia. In studies of cultured cells, we show that this effect is a result of an increase in prolyl hydroxylase-dependent degradation of HIF1alpha.

Influence of hydroxypropyl methylcellulose polymer on in vitro and in vivo performance of controlled release tablets containing alprazolam.

The purpose of this study was to investigate the influence of hydroxypropyl methylcellulose (HPMC) molecular weight on pharmacokinetic and pharmacodynamic parameters of controlled release formulations containing alprazolam. Tablet formulations contained alprazolam, excipients, and either HPMC K4MP or HPMC K100LVP. A ten patient in vivo clinical trial using a randomized, open-label, four-way crossover design was conducted in the fed and fasted states.

Picking alignments from (Steiner) trees.

The application of Needleman-Wunsch alignment techniques to biological sequences is complicated by two serious problems when the sequences are long: the running time, which scales as the product of the lengths of sequences, and the difficulty in obtaining suitable parameters that produce meaningful alignments. The running time problem is often corrected by reducing the search space, using techniques such as banding, or chaining of high-scoring pairs. The parameter problem is more difficult to fix, partly because the probabilistic model, which Needleman-Wunsch is equivalent to, does not capture a key feature of biological sequence alignments, namely the alternation of conserved blocks and seemingly unrelated nonconserved segments.

Characterisation of somatostatin actions on knee joint blood vessels of the rat.

The effects of somatostatin on blood flow, plasma extravasation and knee joint sizes in the rat were investigated. Topical bolus administrations of somatostatin (10 pmol-100 nmol) onto the exposed rat knee joint capsules produced dose-dependent increases in knee joint blood flow with an ED(50) value of 1.7 nmol, and a maximum increase of 109.

Managing perinatal outcomes: the clinical benefit and cost-effectiveness of pharmacologic treatment of recurrent preterm labor.

Purpose: To compare the clinical benefit and cost-effectiveness of utilizing continuous subcutaneous terbutaline versus oral tocolytics following recurrent preterm labor.

Design: Retrospective, 1:1 matched cohort.

Methodology: From prospectively collected data in a nationwide, perinatal database of women receiving outpatient services, we identified singleton gestations having recurrent preterm labor, stabilized during hospitalization, and subsequently treated with oral tocolytics (PO group) or continuous subcutaneous terbutaline infusion (SQ group).

Addition lens alleviates reading-induced ocular stress.

BACKGROUND: Near tasks have been associated with binocular stress to induce myopia. The aim of this study was to investigate the effects of accommodation on reading-induced near heterophoria. METHODS: We measured the near heterophoria of 22 young adults before and after 30 minutes of reading.

Image analysis system for assessment of immunohistochemically stained proliferative marker (MIB-1) in oesophageal squamous cell carcinoma.

The prognosis of oesophageal cancer patients is related to the portion of MIB-1 positively stained tumour nuclei. In this study, an image analysis system was developed based on LEICA Image Processing and Analysis System to reduce the subjective, tedious and inaccurate manual counting of nuclei staining. Representative oesophageal cancer tissues were collected and immunohistochemical preparations of MIB-1 were made.

Limb loss following the use of heparin. A lesson to be remembered.

The optimal method of prophylaxis against venous thromboembolism after total hip replacement (THR) remains uncertain. Most surgeons use some form of pharmacological prophylaxis, most commonly heparin. The precise balance of the benefits and risks is unclear, and serious complications can occur.

Clinical and cost-effectiveness of continuous subcutaneous terbutaline versus oral tocolytics for treatment of recurrent preterm labor in twin gestations.

Objective: To compare the clinical and cost-effectiveness of treating recurrent preterm labor with continuous subcutaneous terbutaline versus oral tocolytics in twin gestations.

Study Design: In a retrospective, matched-cohort design, twin pregnancies treated as outpatients with continuous subcutaneous terbutaline were identified from a perinatal database, then matched 1:1 by gestational age at recurrent preterm labor to those receiving oral tocolytics. There were 353 patients per treatment group.

Adaptive filtering of evoked potentials with radial-basis-function neural network prefilter.

Evoked potentials (EPs) are time-varying signals typically buried in relatively large background noise. To extract the EP more effectively from noise, we had previously developed an approach using an adaptive signal enhancer (ASE) (Chen et al., 1995).

Missense mutations of the fibrillin-1 gene in two Chinese patients with severe Marfan syndrome.

Objective: To describe two Chinese patients with severe forms of Marfan syndrome and to report findings of mutational analysis of the fibrillin-1 (FBN1) gene.

Methods: Two Chinese patients were studied, one suffering from Marfan syndrome of infantile onset and the other of neonatal onset. Their clinical features were described.

Traumatic asymmetrical bilateral hip dislocation in an adult.

Bilateral hip dislocation occurring as a result of trauma is a rare condition. Simultaneous anterior and posterior traumatic dislocation of both hips is even more unusual. A case is reported of asymmetrical bilateral traumatic hip dislocation without an associated fracture of the pelvis or femur occurring in a young adult with no previous history of hip abnormality or ligamentous laxity.

Selection analyses of insertional mutants using subgenic-resolution arrays.

We describe a method of genome-wide analysis of quantitative growth phenotypes using insertional mutagenesis and DNA microarrays. We applied the method to assess the fitness contributions of Escherichia coli gene domains under specific growth conditions. A transposon library was subjected to competitive growth selection in Luria-Bertani (LB) and in glucose minimal media.

Adherence to antibiotics prescribed in an accident and emergency department: the influence of consultation factors.

The objective of this study was to investigate the extent of non-adherence to prescribed antibiotics and the relationship of non-adherence to consultation and attitudinal factors. Self-completion postal questionnaires were sent to 202 consecutive adult attenders to an accident and emergency (A&E) department who had been given antibiotics to take home, within a week of the A&E attendance. The questionnaire included a detailed log of dosing, two sections of eight questions each on the patients' perceptions of the consultation and of their attitudes to medicines in general, which were marked on Likert scales; and questions inviting free text answers.