Intimate Saboteurs

Background: The bariatric patient exists in dynamic relationship with family members and friends who have considerable influence upon the patient and his or her surgical outcome. When family members and friends behave as intimate saboteurs, they attempt to hamper, hurt, or subvert the bariatric patient's goal of achieving and maintaining a healthy body weight. Successful or not, intimate saboteurs provide significant treatment challenges for the patient and the treatment team. Methods and Patients: Patient profiles provide examples of intimate sabotage. The psychological construct of Family Systems Theory is used as a plausible explanation for the sabotage of friends and family. Conclusions: Multidisciplinary professionals treating the bariatric patient must be aware of the critical influence of intimate saboteurs and the tactics they use to sabotage. Treatment guidelines recommended by Family Systems Theory are presented as strategies to mitigate the influence of intimate saboteurs.     

Hormonal profiles and follicular growth in cycles with imminent ovarian hyperstimulation

Ovarian hyperstimulation syndrome is a common and serious complication of human menopausal gonadotrophin/human chorionic gonadotrophin treatment. We evaluated the changes in the pituitary and ovarian hormone profiles and ultrasonographic follicular regression in 12 patients in whom human menopausal gonadotrophin was discontinued due to 'imminent' ovarian hyperstimulation. Following discontinuation, three distinct periods were observed: (i) days 1-2, the levels of oestradiol, testosterone and prolactin, and the total number of follicles continued to rise; (ii) days 3-6, the levels of oestradiol, testosterone and prolactin declined sharply and the total number of follicles was reduced significantly, while the large and medium sized follicles continued to increase. Levels of follicle-stimulating hormone and luteinizing hormone gradually declined to reach their lowest levels by days 5-6 and then increased. (iii) Thereafter the number of follicles and steroid output declined to early follicular phase levels. We conclude that discontinuation of human menopausal gonadotrophin and withholding human chorionic gonadotrophin in cycles with laboratory signs of 'imminent' ovarian hyperstimulation syndrome, allows regression of the ovarian ultrasonographic finding and prevents the development of clinical symptoms. However, if rescue of the cycle is attempted, human chorionic gonadotrophin should be given during the first 4 days after discontinuation of stimulation.     

Controlled Release of Substituted Benzole and Naphthoic Acids Using Carbopol ® Gels: Measurement of Drug Concentration Profiles and Correlation to Release Rate Kinetics

Purpose. The objective of this study is to correlate drug release mechanism with measured drug concentration profiles in gel layers of Carbopol^® matrices containing mesalamine or benzoic acid. Methods. Release rate experiments with Carbopol^® matrices were performed using a rotating disk apparatus. Matrices were frozen and the gel layer in the matrices was sliced using a microtome in a cryostat. Drug concentration profiles were determined by direct measurement of the concentration of the drug in the gel slices. The pH of the slices was measured using microelectrodes, and water content was measured by Karl Fisher titration. Results. The concentration gradient in mesalamine matrices decreased over time and correlated with square root of time release rate kinetics. The concentration profiles of benzoic acid were unchanged over time and correlated with zero order release rate kinetics. Carbopol gel layers were highly hydrated (93–95% water). Gel layers in matrices with mesalamine had a more alkaline microenvironmental pH. This higher pH resulted in increased growth of the thickness of the gel layer and a reduction drug diffusivity in comparison to benzoic acid matrices. Conclusions. The release rate kinetics of mesalamine and benzoic acid correlated to the measured concentration profiles. The shape of the concentration profiles is determined by the rate of growth of the Carbopol^® gel layer and drug diffusivity.     

A study comparing biopharmaceutic characteristics of four once daily controlled release diltiazem preparations

Summary— In the present study we have compared the steady state biopharmaceutic characteristics of four diltiazem once daily controlled release capsules: Mono-Tildiem LP 300® (300 mg), Adizem® XL (300 mg)¹, Cardizem® (300 mg) and Dilacor® (240 mg). Sixteen healthy male volunteers (aged 22.9 ± 3.3 years, range 19–31 years) completed an open label, multiple oral dose, randomized, four-period crossover study without a washout period in between. The volunteers received each diltiazem formulation once daily for four days. Trough diltiazem and metabolites plasma concentrations were determined on days 3 and 4. The 24-h plasma concentration-time profiles were assessed after the dose on day 4 of each period. The following steady state pharmacokinetic parameters for diltiazem were calculated: the minimum plasma concentration (c_min), the maximum plasma concentration (c_max), the time to reach that concentration (t_max), the time interval during which the plasma concentration exceeds 50% of c_max (t₅₀), the area under the plasma concentration-time curve (AUC_72–96) and the peak-to-trough fluctuation (PTF). For the metabolites of diltiazem, N-mono-desmethyl-diltiazem (NDM) and desacetyldiltiazem (DAD), AUC_72–96 (AUC_NDM and AUC_DAD) and the ratio metabolite/parent compound were calculated. Steady state was achieved on day 3. Except one, all controlled release formulations have satisfactory controlled release properties allowing once daily administration. However, significant (P < 0.05) differences were found between the pharmacokinetic characteristics which do not allow exchange of the various formulations. Concentrations well below 50 ng·mL^-1 in the morning hours were observed for Dilacor® (240 mg) and Adizem® XL (300 mg), which could be a disadvantage of these formulations as it is well-known that ischaemic events occur at a higher rate during that part of the day. The plasma concentration profiles of NDM and DAD, the major circulating metabolites, parallel the plasma concentration profiles for the parent compound. From a clinical point of view, all treatments were well tolerated.     

Velocity profiles in the ascending aorta in pigs: Axial development and influence of changes in left ventricular contraction pattern

Summary Earlier studies using hot-film anemometry in pigs have revealed skewed tangentially rotating velocity profiles in the ascending aorta during systole. The reason for this phenomenon has been postulated to be caused by the left ventricular contraction pattern. Therefore, the aim of this study was to investigate the influence of the left ventricular contraction pattern on the velocity fields in the ascending aorta of pigs. We used a 10 MHz perivascular pulsed Doppler ultrasound system to measure point blood velocities at two axial locations over the entire cross sectional area in the ascending aorta of 90 kg pigs. The axial component of the velocity profiles was visualized dynamically by computerized 3-dimensional animation techniques. Changing left ventricular contraction patterns were accomplished by reversible occlusion of either the left anterior descending or right posterior descending coronary artery. The axial development of the systolic rotating and skewed velocity profiles in the ascending aorta was described. The appearance of the systolic velocity profiles were virtually unaffected by changes in left ventricular contraction pattern.This study was kindly supported by The Danish Heart Foundation, Civilingeniør Frode Nyegaard og Hustru's Fond and NOVO's Forskningsfond     

Profile of in Vitro Binding Affinities of Neuroleptics at Different Rat Brain Receptors: Cluster Analysis Comparison with Pharmacological and Clinical Profiles

A series of 21 neuroleptics with different chemical structures (phenothiazines, thioxanthenes, dibenzodiazepines, butyrophenones, benzamides, etc.) was examined for their in vitro interactions with 12 neurotransmitter binding sites in the rat brain (alpha- and beta-noradrenergic, dopaminergic, muscarinic, serotoninergic, histaminic, and opioid receptors, calcium channels, and serotonin uptake binding sites). The biochemical profile obtained from the binding data was compared with reported pharmacological and clinical profiles for this class of compounds by cluster analysis. Cluster analysis on binding data classified the compounds in three main subgroups: benzamides, compounds with an affinity mainly for DA2 and 5-HT2 receptors and inactive at muscarinic receptors, and compounds with a high affinity for alpha 1-adrenergic receptors and muscarinic receptors. The main subgroups resulting from cluster analysis of previously published pharmacological and clinical data for neuroleptics contain compounds common to the present study, with some correlations. The results extend previous observations that a complete binding profile corresponds to the pharmacological and clinical profile of this class of compounds.     

Determination of Red Blood Cell Velocity by Video Shuttering and Image Analysis

A novel modification of conventional video imaging techniques has been developed to determine the velocity of red blood cells (RBCs), which offers compatibility with existing video-based methods for determining blood oxygenation and hemoglobin concentration. Traditional frame-by-frame analysis of video recordings limits the maximum velocity that can be measured for individual cells in vivo to about 2 mm/s. We have extended this range to about 20 mm/s, by electronic shuttering of an intensified charge-coupled device camera to produce multiple images of a single RBC in the same video frame. RBCs were labeled with fluorescein isothiocyanate and the labeled cells (FRBCs) were used as probes to determine RBC velocities in microvessels of the hamster retractor muscle. Velocity was computed as the product of the distance between centroids of two consecutive image positions of a FRBC and the shuttering frequency of the camera intensifier. In vitro calibrations of the system using FRBC and Sephadex beads coated onto a rotating disk yielded an average coefficient of variation of about 6%. Flow conservation studies at bifurcations indicated that the maximum diameter of microvessels below which all the FRBCs in the lumen could be detected was 50 m. The technique was used to estimate mean-FRBC velocity distributions in vessels with diameters ranging from 8 to 50 m. The mean-FRBC velocity profiles were found to be blunter than would be expected for Poiseuille flow. Single FRBCs tracked along an unbranched arteriole exhibited significant temporal variations in velocity. © 1999 Biomedical Engineering Society. PAC99: 8719Tt, 8717Jj, 4279Pw, 8780Tq, 8719Ff, 4230Va, 0705Pj     

应用微阵列初步分析髓母细胞瘤的基因表达谱

目的　应用微阵列技术研究髓母细胞瘤的分子发病机理。方法　收集新鲜髓母细胞瘤 4例及正常脑组织 1份的组织标本 ,提取总 RNA,逆转录成 32 P标记的 c DNA探针 ,与 Atlas人肿瘤芯片杂交 ,通过放射自显影获得基因谱 ,应用 Atlas Image TM1.0 1a分析。结果　与正常脑组织相比 ,髓母细胞瘤下调基因 6个 ,上调基因 35个 ;逆转录 -聚合酶链反应技术验证结果与芯片检测结果相符。除少数基因外 ,大部分基因的表达趋势与肿瘤生物学特性相符。结论　髓母细胞瘤是与星形细胞起源胶质瘤具有不同分子发病机理的多基因病变 ,不同基因之间可能存在复杂的相互作用和联系 ,值得进一步研究。     

Prognostic evaluation before operative extirpation and radiotherapy of solitary brain metastasis

Summary This is a retrospective study of 134 patients operated on for solitary brain metastasis at the University Hospital in Uppsala, Sweden between 1963 and 1982. All the patients underwent postoperative radiation therapy. A statistical evaluation of different prognostic factors was made in order to create a prognostic model, a so-called risk profile, to be used for future patients. The most important factors for the making of risk profiles were found to be the histological diagnosis followed by the location in the brain, then the state on admission and the age at admission in that declining order. All these variables separately and together,i.e., as risk profiles, were matched against the outcome during survival as Karnofsky's scores and against the length of survival time. The results are shown in a diagram giving the surgeon grounds for his decision-making for or against operation and also for pre-operative information.