Disaccharide analysis of human skin glycosaminoglycans in sun-exposed and sun-protected skin of aged people

The negative conduction effect of quinidine on each of the successive phases of the ventricular depolarization was investigated using an original noninvasive method: the spatial velocity electrocardiogram of the QRS complex (SVECG-QRS). We performed a randomized placebo-controlled trial in 10 healthy subjects with a single oral dose of quinidine (330 mg) or placebo. Electrocardiographic acquisition and processing (220 recordings for the complete trial) were performed using the Lyon vectorcardiographic program. For each SVECG-QRS curve, the position of seven specific points from A (onset of QRS) to G (end of QRS) were determined precisely. The six successive time intervals between these points (AB-FG) and five velocity values (B-F) were then calculated. The QRS complex was longer under quinidine than placebo (102.4 +/- 1.6 vs. 100.3 +/- 1.5 ms). The difference was at the periphery of statistical significance (p = 0.05), and this lack of statistical difference may be mainly due to the low serum levels of quinidine obtained at the peak of the concentration (1.46 +/- 0.4 mg/1). All six QRS time intervals were longer under quinidine, but only the BC interval was significantly different (9.3 +/- 1.1 vs. 18.8 +/- 1.1 ms; p < 0.05) suggesting a more pronounced negative conduction effect at the onset of ventricular depolarization. No significant modifications were observed for the velocity values. We conclude that (1) the negative conduction effect of quinidine is heterogeneous, but a further study with a higher dose of quinidine (concentration-dependent effect) is required to confirm this hypothesis and (2) the spatial velocity electrocardiogram of the QRS complex allows a detailed analysis of the ventricular conduction phases. The results of the measurement were found to be reproducible. This noninvasive tool could be used in clinical practice to assess effects of antiarrhythmic drugs on successive ventricular depolarization phases.     

Inhibition of demecolcin-induced DNA synthesis by inhibitors of phospholipase C and protein kinase C

PURPOSE OF STUDY: Interleukin-2 (IL-2) is a potent activator of lymphocytes, but its effectiveness as an anti-cancer agent is compromised by several adverse side effects including pulmonary edema. One explanation for the pulmonary toxicity of IL-2 is that activated lymphocytes directly induce the pulmonary vascular endothelium to become more leaky. METHODS: To test this hypothesis the number of total lymphocytes, gamma delta T cells, and CD2-positive cells (alpha beta T cells and natural killer cells) in peripheral blood and lung lymph of sheep were compared before and after IL-2 infusion. Hemodynamic and lymph dynamic changes were also evaluated. RESULTS: IL-2 decreased mean aortic pressure, increased cardiac output, lowered systemic vascular resistance, and doubled lung lymph flow (P < or = 0.05), but had no effect on plasma or lymph oncotic pressure. The lymph protein concentration and the lymph-to-plasma protein concentration ratio were not different after IL-2 infusion. IL-2 had no effect on the number of total lymphocytes, gamma delta T cells, or CD2-positive cells in the peripheral blood. In contrast, the number of total lymphocytes, gamma delta T cells, and CD2-positive cells in lung lymph decreased significantly (P < or = 0.05). CONCLUSIONS: The lymphocyte populations decreased more than could be explained by the increase in lymph flow, demonstrating that lung lymphocytes were not reduced simply by dilution. These results imply that the pulmonary edema associated with IL-2 is not caused by activated lymphocytes.     

Global folds of highly deuterated, methyl-protonated proteins by multidimensional NMR

The development of 15N, 13C, 2H multidimensional NMR spectroscopy has facilitated the assignment of backbone and side chain resonances of proteins and protein complexes with molecular masses of over 30 kDa. The success of these methods has been achieved through the production of highly deuterated proteins; replacing carbon-bound protons with deuterons significantly improves the sensitivity of many of the experiments used in chemical shift assignment. Unfortunately, uniform deuteration also radically depletes the number of interproton distance restraints available for structure determination, degrading the quality of the resulting structures. Here we describe an approach for improving the precision and accuracy of global folds determined from highly deuterated proteins through the use of deuterated, selectively methyl-protonated samples. This labeling profile maintains the efficiency of triple-resonance NMR experiments while retaining a sufficient number of protons at locations where they can be used to establish NOE-based contacts between different elements of secondary structure. We evaluate how this deuteration scheme affects the sensitivity and resolution of experiments used to assign 15N, 13C, and 1H chemical shifts and interproton NOEs. This approach is tested experimentally on a 14 kDa SH2/phosphopeptide complex, and a global protein fold is obtained from a set of methyl-methyl, methyl-NH, and NH-NH distance restraints. We demonstrate that the inclusion of methyl-NH and methyl-methyl distance restraints greatly improves the precision and accuracy of structures relative to those generated with only NH-NH distance restraints. Finally, we examine the general applicability of this approach by determining the structures of several proteins with molecular masses of up to 40 kDa from simulated distance and dihedral angle restraint tables.     

Gas exchange function of the middle ear in patients with otitis media with effusion

Gas exchange function through the middle ear mucosa was assessed using nitrous oxide (N2O) in patients with otitis media with effusion (OME), as well as in normal ears during elective surgery for unrelated disorders. In all normal ears except one (n = 43), an increase in pressure was observed after N2O inhalation. In 42 of 84 ears with OME, a pressure increase was observed, but not in the remaining 42 ears (50%), indicating that the gas exchange function in these latter ears was impaired. In 21 of the 42 ears showing no middle ear pressure increase following N2O inhalation, the middle ear pressure was again monitored after myringotomy and aspiration of the effusion A pressure increase was found in 16 ears, indicating that the impairment in gas exchange function in ears with OME may be reversible in most cases. Computed tomography of the mastoid was examined preoperatively in 66 ears, with the presence or absence of a middle ear pressure change well correlated in 57 ears with the presence or absence of mastoid aeration.     

Dyspnea resulting from phrenic nerve paralysis after interscalene brachial plexus block in an obese male--a case report

While current psychiatric taxonomies recognise a classification of amphetamine dependence, derived from the notion of an alcohol dependence syndrome, little research has validated that such a condition exists for this drug. Current amphetamine users (N = 331), were interviewed using the World Health Organization operationalisation of DSM-III-R substance dependence criteria, and a measure of the psychological components of dependence. Structural analyses indicated that a unidimensional dependence syndrome as assessed by DSM-III-R and DSM-IV criteria exists for amphetamine, and that physiological, psychological and behavioural indicators were all important in accounting for the variance in responses. It was demonstrated that the concept of a dependence syndrome is applicable to amphetamine, and that the inclusion of the amphetamine dependence syndrome in DSM-III-R and DSM-IV is valid.     

Effect of arginine vasopressin (AVP) inhibitor in the inhibition of the peritumoral edema

BACKGROUND: Major depressive disorder is often marked by repeated episodes of depression. We describe recovery from major depression across multiple mood episodes in patients with unipolar major depression at intake and examine the association of sociodemographic and clinical variables with duration of illness. METHODS: A cohort of 258 subjects treated for unipolar major depressive disorder was followed up prospectively for 10 years as part of the Collaborative Depression Study, a multicenter naturalistic study of the mood disorders. Diagnoses were made according to the Research Diagnostic Criteria, and the course of illness was assessed with the Longitudinal Interval Follow-up Evaluation. Survival analyses were used to calculate the duration of illness for the first 5 recurrent mood episodes after recovery from the index episode. RESULTS: Diagnosis remained unipolar major depressive disorder for 235 subjects (91%). The median duration of illness was 22 weeks for the first recurrent mood episode, 20 weeks for the second, 21 weeks for the third, and 19 weeks for the fourth and fifth recurrent mood episodes; the 95% confidence intervals were highly consistent. From one episode to the next, the proportion of subjects who recovered by any one time point was similar. For subjects with 2 or more recoveries, the consistency of duration of illness from one recovery to the next was low to moderate. None of the sociodemographic or clinical variables consistently predicted duration of illness. CONCLUSION: In this sample of patients treated at tertiary care centers for major depressive disorder, the duration of recurrent mood episodes was relatively uniform and averaged approximately 20 weeks.     

Paracetamol poisoning in the north east of England: presentation, early management and outcome

1. Paracetamol is increasingly involved in self-poisoning in the United Kingdom and remains a common cause of fatal poisoning. 2. To document the epidemiology and early management of paracetamol poisoning data were collected on consecutive patients with suspected paracetamol poisoning presenting to 6 hospitals in the North East of England over 12 weeks in 1994. 3. There were 400 presentations (attendance rate 1.14/10(3) population/yr) involving 343 persons (45% male). Paracetamol concentrations at 4 h correlated weakly with reported paracetamol dose (R = 0.49, P < 0.0001) and were similar comparing those treated and not treated by gastric decontamination. 4. In 38 (9%) cases paracetamol concentrations were above the appropriate nomogram treatment line, including 3% and 20% of patients who reported ingesting less than and more than 12 g respectively. In 21 patients acetylcysteine treatment was deferred until admission to the ward, the mean delay involved was 2.8 h. 5. One patient died, from arrhythmias caused by co-ingested dothiepin. 6. Paracetamol poisoning is common. Most cases do not have potentially toxic plasma paracetamol concentrations, but those who do often present late and antidotal treatment may be delayed inappropriately.     

Precise rendering method for exact anti-aliasing and highlighting

This paper introduces the Precise Rendering Method, which generates accurately anti-aliased and highlighted images from tessellated polygons. The Precise Rendering Method first solves the aliasing problems of hidden surface removal by using the Cross Scanline Algorithm. This algorithm can exactly calculate polygon areas projected onto each pixel by using horizontal and vertical scanlines. Aliasing artifacts in shading are then prevented by the Reflection Intergration Method, which analytically integrates the intensity of reflection in the solid angle defined by surface normals at vertices of the projected area. Several synthesized images are created to show the efficiency of the Precise Rendering Method.     

Prenatal diagnosis of an extensive fetal lymphangioma using ultrasonography, magnetic resonance imaging and cytology

An unusual case of fetal lymphangioma diagnosed before delivery is reported in a second trimester pregnant woman. The lymphangioma was suspected at 28 weeks on the basis of the ultrasound appearances and progression of the lesions with advancing gestation. MRI was used to evaluate the extent and the tissue characteristics of the lesions. Cytology of the fluid aspirated from the cystic lesions showed abundant lymphocytes and macrophages, confirming the diagnosis of a lymphangioma. The parents opted for a pregnancy termination because of the rapid growth of the lesions and the poor prognosis. It is suggested that the combination of these tests could enable the early diagnosis of these tumours at a stage when the lesion is relatively limited and accessible to therapy in utero.