Improved column-switching liquid chromatographic method for the determination of the enantiomers of mefloquine

A liquid chromatographic method for the determination of the enantiomers of mefloquine has been improved. The chromatography involved two columns: an achiral cyanopropyl stationary phase for the quantification of (+/-)-mefloquine and a chiral naphthyl-urea stationary phase for the determination of the enantiomeric ratio. Compared with the previous method, which needed two detectors, this one used one detector-integrator to which the two columns are connected alternately by an automated column-switching system. The method is suitable for the quantification (0.05 microgram/ml) of mefloquine and the determination of enantiomeric ratios from 500-microliters plasma samples with ultraviolet detection.     

Cisapride reduces neonatal postoperative ileus: randomised placebo controlled trial

AIM: To assess the efficacy of cisapride in reducing ileus persisting to the tenth postoperative day after neonatal abdominal surgery. METHODS: A prospective, randomised, double blind trial comparing rectal cisapride (1.4-2.3 mg/kg/day) with placebo over seven days was undertaken in 33 neonates. RESULTS: Seven of 12 (58%) patients receiving placebo and eight of 11 (73%) receiving cisapride achieved a first sustained feed during treatment. Of those receiving cisapride, the first sustained feed occurred at 2.3 days (SEM 0.6) compared with 4.7 days (SEM 0.8) with placebo. By the seventh day the mean daily net enteral balance was 69 (SEM 18) ml/kg in the cisapride subgroup and 17 (SEM 8) ml/kg for those receiving placebo. Stool was passed on 6.3 (SEM 0.4) treatment days in the cisapride subgroup compared with 4.1 (SEM 1.0) treatment days in the placebo subgroup. CONCLUSION: Cisapride is effective in neonates with a prolonged ileus after abdominal surgery.     

Records of change in salt marshes: a radiochronological study of three Westerschelde (SW Netherlands) marshes

Three salt marshes on a 50-km transect along the north bank of the Westerschelde Estuary were investigated to determine whether salt marshes in the estuary had responded to shipping channel modifications in recent decades. Marsh accretion rates were estimated mainly from 137Cs profiles with further evidence from 241Am because changes in both rate of deposition and nature of the accreting material precluded use of standard 210Pb(excess) dating models. The 137Cs profiles usually show peaks corresponding to atmospheric deposition from the 1963 fallout maximum and sometimes from the Chernobyl accident, although intervening enhanced 137Cs activities derived from the nuclear reprocessing marine discharges of Sellafield and La Hague are clearly discernible. In all three marshes (Ritthem at the mouth of the estuary and Zuidgors and Waarde at 20 and 45 km upstream), a marked, near-coincident change in the rate of accumulation and in the grain size of material deposited occurred around 1980. This may be related to a combination of channel deepening and straightening operations undertaken in the mid-1970s and/or natural changes in winter wave climate.     

The synthesis and in vitro characterization of the mucoadhesion and swelling of poly(acrylic acid) hydrogels

Depression is a significant problem in epilepsy. Suicides occur in epileptic patients five times more often than in general population. Material included 34 epileptics with 76 suicidal attempts and 24 patients with no history of suicide. Psychical state was studied with Beck Depression Inventory and Hamilton Depression Rating Scale. In the group with suicidal attempts 65% of patients had depression (54.5% of them had major depression) and in group without suicide attempts depression was noted in 54% (23% with major depression). Patients with depression were divided into two groups: group I with suicidal attempts and group II without history of suicide. In group I more patients were alcohol abusers (50% vs 31%), more were treated because of epilepsy longer than 10 years (59% vs 46%) and more had tonic-clonic seizures (82% vs 46%). In group I, 54% of patients were on polytherapy (more than half of them with fenobarbital). In group II, 31% of epileptics were on polytherapy (no one with fenobarbital). Major depression was significantly more frequent in epileptics with suicidal attempts. The severity of depression may influence the risk of suicide. Major depression may be associated with late age of onset of epilepsy, longer treatment duration, tonic-clonic seizures, polytherapy (mainly with fenobarbital) and alcohol abuse.     

Glutathione and catalase provide overlapping defenses for protection against hydrogen peroxide in the yeast Saccharomyces cerevisiae

Glutathione (GSH) is an abundant and ubiquitous low-molecular-weight thiol which has proposed roles in many cellular processes including protection against the deleterious effects of reactive oxygen species. Our experiments have addressed the role of GSH in protection against hydrogen peroxide in the yeast Saccharomyces cerevisiae, and have shown that GSH and catalase provide overlapping defense systems. GSH appears to be the primary antioxidant for protection against hydrogen peroxide since mutants lacking GSH (gsh1) or glutathione reductase (glr1) are sensitive, whereas, strains lacking catalase A (cta1) or catalase T (ctt1) are unaffected in resistance to this oxidant. Furthermore, following treatment with hydrogen peroxide, the levels of oxidized, protein-bound and extracellular GSH were all increased at the expense of intracellular GSH. However, there are two lines of evidence that indicate catalases are required in the absence of GSH; firstly, strains that lack both catalase A and T accumulate increased levels of oxidized glutathione following treatment with hydrogen peroxide; and secondly, deletion of catalase genes exacerbates the hydrogen peroxide sensitivity of glr1 and gsh1 mutants.     

Saving Sergeant Buske. An account of remarkable valor and amazing survival from the records of the 65th General Hospital, a Duke University Army Reserve Unit of World War II

BACKGROUND: Attentional processes are assumed to play an important role in the maintenance of illness anxiety, although empirical support is relatively scarce. METHODS: The present study explores the relationship between selective attention (i.e. private body consciousness and symptom reporting), intensive concentration (i.e. attentional control and sustained attention), and illness anxiety in 57 non-clinical subjects. RESULTS: Zero-order and multiple correlations suggest that illness anxiety is significantly related to cognitive failures in everyday life and private body consciousness and to a lesser extent to symptom reporting. CONCLUSION: It is concluded that illness anxiety can be partly predicted from specific attentional variables. However, specific operationalizations of attentional parameters seems to determine the existence and magnitude of these relations.     

A pilot study of lithium carbonate plus divalproex sodium for the continuation and maintenance treatment of patients with bipolar I disorder

PURPOSE OF STUDY: To assess whether selected periapical radiographs, taken according to High Yield Criteria, can reveal as much intra-osseous pathology as universal panoramic screening. POPULATION STUDIED: The records of 1101 RAF recruits enlisted in 1988-89, average age 19 years (range 16-26). METHODS: The clinical records and bitewing radiographs of the recruits were examined and the requirement for periapical radiographs determined according to high yield criteria. A template, cut out to simulate the area covered by a periapical bitewing radiograph, was placed over the suspect region on the panoramic film and any findings found within the template recorded. The entire dental panoramic tomograph was then examined on a masked screen under 2X magnification and any further findings recorded. FINDINGS: There was a considerable number of findings reported, including three large isolated radiolucent areas, 75 periradicular radiolucent areas, four probable cysts and 1187 unerupted mandibular third molars. However, when the clinical significance of these 'lesions' was assessed only those related to dental causes appeared to have significant clinical implications and the results indicated that these could have been detected by selective radiology. CONCLUSION: This study showed that the only pathology which occurs frequently enough to justify radiographic screening of the jaws in young adults is related to teeth. It seems probable that this type of pathology can be at least as well detected by selective periapical screening, using high yield criteria, as is possible by universal panoramic screening.     

Tuft-to-capsule adhesions and their precursors: differences between the vascular and tubular poles of the human glomerulus

The hypothalamo-pituitary-adrenal (HPA) axis is modulated by sex hormones. Few data exist on the relation between acute estrogen deficit and HPA axis response to corticotropin-releasing hormone (CRH). The effects of a sudden drop in estradiol levels on basal and CRH-stimulated levels of ACTH, cortisol, testosterone, androstenedione and 17-hydroxyprogesterone (17-OHP) were assessed in nine premenopausal women (44-48 years of age), before and after ovariectomy. The CRH test was performed before and 8 days after ovariectomy. A significant reduction in ACTH and adrenal steroids but not in cortisol response to CRH was observed after ovariectomy. The ratio of deltamax androstenedione/17-OHP after CRH stimulation was substantially the same before and after ovariectomy, whereas deltamax 17-OHP/cortisol was significantly lower in ovariectomized women showing increased 21- and 11beta-hydroxylase activity. The results show that the acute estrogen deficit induces changes in the HPA axis characterized by reduced stimulated secretion of ACTH and steroids but normal stimulated cortisol production.     

The identification of nonlinear biological systems: Volterra kernel approaches

Representation, identification, and modeling are investigated for nonlinear biomedical systems. We begin by considering the conditions under which a nonlinear system can be represented or accurately approximated by a Volterra series (or functional expansion). Next, we examine system identification through estimating the kernels in a Volterra functional expansion approximation for the system. A recent kernel estimation technique that has proved to be effective in a number of biomedical applications is investigated as to running time and demonstrated on both clean and noisy data records, then it is used to illustrate identification of cascades of alternating dynamic linear and static nonlinear systems, both single-input single-output and multivariable cascades. During the presentation, we critically examine some interesting biological applications of kernel estimation techniques.     

Design and synthesis of a series of potent and orally bioavailable noncovalent thrombin inhibitors that utilize nonbasic groups in the P1 position

As part of an ongoing effort to prepare therapeutically useful orally active thrombin inhibitors, we have synthesized a series of compounds that utilize nonbasic groups in the P1 position. The work is based on our previously reported lead structure, compound 1, which was discovered via a resin-based approach to varying P1. By minimizing the size and lipophilicity of the P3 group and by incorporating hydrogen-bonding groups on the N-terminus or on the 2-position of the P1 aromatic ring, we have prepared a number of derivatives in this series that exhibit subnanomolar enzyme potency combined with good in vivo antithrombotic and bioavailability profiles. The oxyacetic amide compound 14b exhibited the best overall profile of in vitro and in vivo activity, and crystallographic studies indicate a unique mode of binding in the thrombin active site.