Rheological characterisation of dextran-concanavalin A mixtures as a basis for a self-regulated drug delivery device.

The rheological characterisation of glucose sensitive mixtures containing dextran and concanavalin A (con A) with and without glucose, was undertaken using oscillatory rheometry at 20 and 37 degrees C so that comparative data could be gathered in the linear viscoelastic (LVE) range. Measurements for a series of mixtures showed that complex viscosity is a function not only of the con A concentration but of the content and molecular weight of the dextran used. The extent of liquefaction on addition of glucose also depended on these factors. The tan delta profiles confirmed the change from semi-solid towards fluid behaviour. This occurs when glucose effects dismantling of the three-dimensional structure of the dextran-con A system by competitive binding to the glucose receptors in the protein. For the mixtures studied, the changes occurred between contents of 0 and 1% (w/w) glucose at 20 and 37 degrees C and form a useful basis for the formulation of a self-regulating delivery device for the control of hyper-and hypoglycaemia in diabetes.     

Maternal Position at Midwife‐Attended Birth and Perineal Trauma: Is There an Association?

ABSTRACT: Background: Most women will sustain some degree of trauma to the genital tract after vaginal birth. This study aimed to examine the association between maternal position at birth and perineal outcome in women who had a midwife‐attended, spontaneous vaginal birth and an uncomplicated pregnancy at term. Methods: Data from 3,756 births in a major public tertiary teaching hospital were eligible for analysis. The need for sutures in perineal trauma was evaluated and compared for each major factor studied (maternal age, first vaginal delivery, induction of labor, not occipitoanterior, use of regional anesthesia, deflexed head and newborn birthweight >3,500 g). Birth positions were compared against each other. Subgroup analysis determined whether birth positions mattered more or less in each of the major factors studied. The chi‐square test was used to compare categorical variables. Results: Most women (65.9%) gave birth in the semi‐recumbent position. Of the 1,679 women (44.5%) who required perineal suturing, semi‐recumbent position was associated with the need for perineal sutures, whereas all‐fours was associated with reduced need for sutures; these associations were more marked in first vaginal births and newborn birth weight over 3,500 g. When regional anesthesia was used, semi‐recumbent position was associated with a need for suturing, and lateral position associated with a reduced need for suturing. The four major factors significantly related to perineal trauma included first vaginal birth, use of regional anesthesia, deflexed head, and newborn weight more than 3,500 g. Conclusions: Women should be given the choice to give birth in whatever position they find comfortable. Maternity practitioners have a responsibility to inform women of the likelihood of perineal trauma in the preferred birth position. Ongoing audit of all clinicians attending births is encouraged to further determine effects of maternal birth position and perineal trauma, to investigate women's perception of comfortable positioning at birth, and to measure changes to midwifery practice resulting from this study.     

Efficient 12-mutation testing in the CFTR gene: a general model for complex mutation analysis

The identification of the cystic fibrosis transmembrane conductanceregulator (CFTR) gene has led to the identification of morethan 225 presumed disease-causing mutations at the locus. Thediagnosis of cystic fibrosis or the carrier state by directDNA analysis is hindered by this large number. A practical assaymust be able to detect enough mutations to achieve clinicallysignificant sensitivity. The use of allele-specifk oligonucleotideprobes is the most promising of the available methods. However,to date this has generally involved tedious probe-by-probe hybridizations,due to variations in the oligonucleotides' denaturation temperaturescaused by differences in their G-C base-pair content. We havedeveloped a rapid, cost-effective assay that simultaneouslydetects 12 CFTR mutations after multiplex polymerase-chain-reactionamplification of genomic DNA. The test may be readily extendedto detect additional mutations at minimal increase in the costper test or the turnaround time. We improve specificity andavoid the need for individual hybridizations by the use of tetramethylammoniumchloride to virtually eliminate the effects of G-C differences.Coupled with non-invasive sample-collection methods, this isan immediately practical assay for cystic fibrosis. More generally,it will serve as a model for the development of diagnostic testsin other genetic disorders involving complex mutation analysis.     

Ureteral obstruction in the neonatal rat: Renal nerves modulate hemodynamic effects

In the neonate, chronic unilateral ureteral obstruction (UUO) reduces renal blood flow (RBF) of the ipsilateral kidney and increases RBF of the opposite kidney. To determine whether renal nerves mediate or modulate these responses complete left UUO in the neonatal rat was used as a model of severe obstructive uropathy, and was compared with sham-operated controls. At 24–28 days of age, animals underwent left or right mechanical renal denervation or left sham renal denervation. One week after denervation, animals were anesthetized and blood pressure and heart reate were measured. Cardiac output and RBF were determined by the radioactive microsphere technique. UUO increased blood pressure and heart rate, and decreased RBF in the obstructed kidney, regardless of denervation. While left UUO increased RBF to the intact opposite kidney in rats with left renal denervation, this was attenuated by right renal denervation. Thus, in the neonatal rat, UUO modulates systemic renal hemodynamics, possibly through activation of the renin-angiotensin system. While renal nerves do not mediate the vasoconstriction of the obstructed kidney, renal nerves modulate vascular tone of the kidney contralateral to UUO.     

Marital Functioning in Early Versus Late-Onset Alcoholic Couples

Current knowledge about alcohol and marital functioning is limited by restrictive sample selection, inattention to the literature on individual-based alcoholic subtypes, and lack of research linking individual differences among alcoholics to marital functioning. The present study was designed to study marital functioning of alcoholics in light of current alcohol typologies. Subjects were part of a larger study on conjoint treatment of alcoholic males and their female partners. Four typologies—including Type 1/2, In-Home/Out-of-home, SteadyIEpisodic, and EarlyILate Onset—were tested for replicability and discriminant validity before linking them to marital functioning. Discriminant validity was found only for the Early (59%)-versus Late (41 %)-Onset typology; thus, further analyses linked only this typology with marital functioning. At baseline, Early-Onset couples reported more marital instability, and the females in these couples were more distressed. During treatment, Early-Onset couples reported higher daily marital satisfaction than Late-Onset couples. Regardless of age of onset, males reported higher marital satisfaction than their spouses during treatment, but their satisfaction did not increase during treatment. Female partners' marital satisfaction increased during treatment. Female partners of Late-Onset males reported particularly low marital satisfaction during treatment. Parsing the sample according to the early-/late-onset typology yielded different predictors of marital satisfaction for males and females within each subtype. For female partners of Early-Onset alcoholics, psychological distress unrelated to her pattner's drinking severity was most associated with her own marital satisfaction, whereas marital adjustment of female partners of Late-Onset alcoholics was most associated with the male's level of perceptual accuracy regarding her needs. This pattern was reversed for the males; marital adjustment of Early-Onset alcoholics was most associated with his partner's perceptual accuracy of his needs, whereas marital functioning of Late-Onset alcoholics was best accounted for by his own psychological distress.     

Survival, mutagenesis, and host cell reactivation in a Chinese hamster ovary cell ERCC1 knock-out mutant

Positive selection-negative selection gene targeting was usedto disrupt the nucleotide excision repair gene ERCC1 in a Chinesehamster ovary cell line, CHO-K1. Southern and Northern analysisshowed that a cell clone isolated by this targeting approach,CHO-7-27, had an ERCC1 gene structure consistent with targeteddisruption of ERCC1 exon V, and did not express ERCC1 mRNA.CHO-7-27 was further characterized with respect to UV and mitomycinC sensitivities, and was shown to exhibit severe mutagen sensitivityphenotypes consistent with those of other CHO cell ERCC1 mutants.Mutation frequency experiments showed that CHO-7-27 was UV-hypermutableat the hypoxanthine-guanine phosphoribosyltransferase locus.Experiments assessing host cell reactivation of viral DNA synthesisfor UV-irradiated adenovirus showed that CHO7-27 exhibited aseverely deficient HCR phenotype similar to that of UV20 cells.Our results demonstrate that CHOK1 cells are hemizygous forthe ERCC1 gene, and show that the comparatively mild mutagensensitivities and lack of severely deficient HCR phenotypesof conventionally derived CHO-K1 ERCC1 mutants, in contrastto the severe phenotypes of CHO-AA8-derived mutants, are notdue to any intrinsic genetic differences between CHO-K1 andCHO-AA8 parental cell lines. ⁴To whom correspondence should be addressed     

The modified Evan's blue dye procedure fails to detect aspiration in the tracheostomized patient: Five case reports

The modified Evan's blue dye procedure (MEBD) is a method of performing tracheal suctioning of the patient through the tracheostomy tube after administration of color-contrasted food and liquid. The MEBD is done when radiographic or fiberoptic procedures are not available or practical. In 5 tracheostomized patients, the MEBD does not detect aspiration.     

The Effect of Flurbiprofen on Steady-State Plasma Lithium Levels

Study Objective . To evaluate the effects of flurbiprofen therapy on the pharmacokinetics of lithium. Design . Placebo-controlled, single-blind, crossover study. Setting . University-affiliated hospital. Patients . Eleven healthy women with bipolar disorder. Interventions . The subjects received therapeutic doses of lithium administered as an immediate-release capsule every 12 hours. In addition, they received one placebo tablet every 12 hours during phase I and flurbiprofen 100 mg every 12 hours during phase II of the study. Measurements and Main Results . Steady-state pharmacokinetic parameters were measured for each phase. Lithium trough plasma concentration (C_min) and area under the curve were statistically significantly increased (p<0.05) when patients received flurbiprofen. Flurbiprofen also caused decreases in lithium clearance and 24-hour lithium urine excretion, although the changes did not reach statistical significance. Clinically significant increases in C_min appeared to be associated with a greater than 1000-μg/24 hour decrease in urinary excretion of prostaglandin E₂. Conclusion . Patients with clinically normal renal function may experience an increase in lithium levels with the initiation of flurbiprofen therapy.