Use of intranasal IL-12 to target predominantly Th1 responses to nasal and Th2 responses to oral vaccines given with cholera toxin

We have investigated the effects of IL-12 and cholera toxin (CT) on the immune response to tetanus toxoid (TT) given by intranasal or oral routes. CT inhibited IL-12-induced IFN-gamma secretion both in vivo and in vitro. Intranasal administration of IL-12 to mice nasally immunized with the combined vaccine of TT and CT resulted in increased TT-specific IgG2a and IgG3 Abs, while IgG1 and IgE Ab responses were markedly reduced. This shift of the CT-induced immune response toward Th1 type was associated with TT-specific CD4+ T cells secreting IFN-gamma and reduced levels of Th2-type cytokines (i.e., IL-4, IL-5, IL-6, and IL-10). In contrast, intranasal IL-12 enhanced the CT-induced serum IgG1 and IgE Ab responses in mice given the combined vaccine orally. IFN-gamma secretion by TT-specific CD4+ T cells was also enhanced; however, Th2-type cytokine responses were predominant. Mucosal secretory IgA responses to oral or nasal vaccines were not affected by intranasal IL-12. Thus, intranasal IL-12 delivery influences Th cell subset development in mucosal inductive sites that are dependent on the route of vaccine delivery.     

Direct determination of asymptotic structural postbuckling behaviour by the finite element method

Application of the finite element method to Koiter's asymptotic postbuckling theory often leads to numerical problems. Generally it is believed that these problems are due to locking of non-linear terms of different orders. A general method is given here that explains the reason for the numerical problems and eliminates these problems. The reason for the numerical problems is that the postbuckling stresses are inaccurately determined. By including a local stress contribution, the postbuckling stresses are calculated correctly. The present method gives smooth postbuckling stresses and shows a quick convergence of the postbuckling coefficients. © 1998 John Wiley & Sons, Ltd.     

Nosocomial infection following cardiovascular surgery: comparison of two periods, 1987 vs. 1992

BACKGROUND: QT dispersion has been proposed as a simple, noninvasive measure for identifying patients at risk of postinfarction arrhythmia. It is assumed to reflect nonuniform ventricular repolarization, which, in turn, may result from regional differences in repolarization time as well as from localized activation delay. The aim of this study was to examine the relation between QT dispersion and intraventricular conduction abnormalities in patients with acute anterior wall myocardial infarction. METHODS AND RESULTS: Standard 12-lead electrocardiographic and 12-lead signal-averaged electrocardiographic recordings were performed in 25 patients with a first Q-wave anterior wall myocardial infarction. Measures calculated by using the 6 precordial (V1 through V6) leads for QT dispersion were (1) difference between maximum and minimum QT and QTc intervals and (2) standard deviation of QT and QTc intervals. Measures calculated from the signal-averaged electrocardiogram were (1) maximum filtered QRS duration; (2) mean; and (3) standard deviation of filtered QRS duration. No relation was found between any measure of filtered QRS duration and that of QT dispersion by using linear correlation analysis. Similarly, no significant association was demonstrated between the filtered QRS duration and corresponding QT interval measurements (total 131 leads). CONCLUSIONS: The lack of correlation between signal-averaged electrocardiogram indexes of slow intraventricular conduction and electrocardiogram variables of QT dispersion suggests an independent predictive value for the 2 methods in identifying patients at risk of postinfarction arrhythmia. This suggestion is further supported by the finding that altered activation sequence is an unlikely mechanism of QT dispersion in patients with acute myocardial infarction, as indicated by the lack of association between the filtered QRS duration and corresponding QT interval measurements.     

Microcirculatory disorders in cerebral ischemia in rats and their correction by using leu-enkephalin

Leu-enkephalin (LE) induced mainly a constriction of pial arterioles, diameter of the venules did not change. The effect of the LE involved preservation of the cerebral blood flow and that in microvessels, constriction of some arterioles and reduced dilatation against the background of decreased arterial pressure, bradycardia, increased lymphatic flow and survival of the animals during first hours of occlusion of common carotid arteries.     

Pharmacoeconomics of intravenous antibiotic use in serious infection

A pharmacoeconomic study of 15 antibiotics available in Barbados was performed. The antibiotics studied were amoxycillin/clavulanate, ampicillin, ampicillin/sulbactam, cefazolin, cefotaxime, ceftazidime, ceftriaxone, clindamycin, cloxacillin, cotrimoxazole, gentamicin, imipenem, metronidazole, piperacillin, piperacillin/tazobactam, and vancomycin. The costs of use of these compounds were calculated for a five-day course using a formula comprising eight categories: antibiotic purchase cost, maintenance of intravenous access, drug delivery cost, drug monitoring cost, dose readjustment, general monitoring cost, 'sharps' disposal cost and adverse effects. The costs of adverse effects were not included in this study due to lack of accurate data. The total cost of antibiotic use (in U.S. dollars) ranged from $42.52 to $463.73 per five-day course. Generic compounds were less expensive ($45.52 - $98.23) than brand-name compounds ($106.18 - $106.18 - $463.73). Antibiotic purchase costs accounted for proportions of total costs ranging from 7 to 93%. Non-drug costs represented a much greater proportion of total costs of generic compounds. For most compounds the non-drug costs were related to the frequency of dosing, but for gentamicin the non-drug costs were relatively higher because of the need for monitoring of serum gentamicin levels. Efficacy and freedom from side-effects will remain the most important determinants in the choice of antibiotic therapy. However, pharmacoeconomic analyses can provide prescribers with the information required to make cost-effective choices for treatment of their patients.     

Osteonecrosis of the femoral head. Hip salvaging with implantation of a vascularized fibular graft

The authors tried to save the hip joint by implanting a vascularized fibular graft, augmented with cancellous bone, into the curetted core of the femoral head that was affected by aseptic necrosis. Forty of 66 hips were observed for a minimum of 20 months and for as long as 66 months (average, 32 months). Clinical assessment according to the cause and severity of the disease was done using the Harris Hip Score. Twenty-eight hips (70%) were rated excellent, 7 (17.5%) were good, 2 (5%) were fair, and 3 (7.5%) failed and were replaced with an artificial joint. Clinically satisfactory results, including good and excellent, were obtained in 35 hips (87.5%). Radiographic evaluation showed improved appearance of the femoral head core in all 15 patients (37.5%) operated on at a precollapse stage of the disease. In 20 hips, the deformity of the femoral head was unchanged (50%), 2 (5%) became worse, and 3 (7.5%) failed. The number of hips with improved appearance as shown on radiographs and those in which the process was unchanged equaled the number of hips with satisfactory clinical results. These data show that the procedure can induce new bone formation that fuses with the affected subchondral bone, thus preventing the articular surface from collapse. This suggests that vascularized fibular grafting is an excellent alternative for hip salvaging when treating femoral head osteonecrosis.     

Mutational activation of the Cpx signal transduction pathway of Escherichia coli suppresses the toxicity conferred by certain envelope-associated stresses

Anticipation and suspicion are critical aspects to any discussion of intrauterine adhesions. Curettage between the second and fourth week postpartum is more likely to cause adhesions than is any other endometrial trauma. Infertility, recurrent abortion, or menstrual aberrations after any uterine trauma should cause the physician to suspect the presence of intrauterine adhesions. Hysterosalpingography and hysteroscopy are the ideal methods to make the diagnosis of IUA, and the latter is the safest, least traumatic, and most precise method of treating adhesions. The addition of an intrauterine splint and high-dose estrogen therapy completes the therapeutic approach. Before attempting conception the cavity should be inspected to verify its normality.     

Variability in function measurements of three sensory foot nerves in neuropathic diabetic patients

Although most short, linear peptide fragments of proteins are unstructured in aqueous solution, a number of immunogenic and antigenic peptides have been shown to have conformational preferences for structured forms. By using mainly NMR and CD spectroscopy, it has been possible to detect and quantify quite small populations of beta-turn, helical, and nascent helical conformations. Recent studies have been published indicating that the presence of structured forms is correlated with the location of T cell and/or B cell epitopes in peptide sequences. X-ray crystal structures of complexes between peptides and anti-peptide antibodies frequently show the peptides bound in beta-turn conformations, and the presence of helix in one peptide-antibody complex has been shown by NMR spectroscopy. Studies of peptides free in solution and bound to anti-peptide antibodies in the crystal indicate that the structure of the principal neutralizing determinant of HIV-1 probably includes at least one beta-turn in a highly conserved region. These results can potentially be used in the design of peptide-based vaccines.     

Plasma from women with preeclampsia increases endothelial cell nitric oxide production

In preeclampsia, a factor in the maternal circulation alters endothelial function via a reduction in nitric oxide synthesis. We measured the in vitro effects of 2% plasma from women with preeclampsia, compared with 2% plasma from normotensive pregnant women, on cultured endothelial cell nitrite production and nitric oxide synthase activity. On finding differential effects, we measured the effects on cellular viability (assessed by lactate dehydrogenase levels) and performed a time course study. Endothelial cell nitrite production was found to be higher after exposure to plasma from the preeclamptic group than the normotensive pregnant group. The effects of long-term exposure (120 hours) were similar to those of short-term exposure (24 hours). In addition, nitric oxide synthase activity was significantly greater after exposure to preeclamptic plasma than after exposure to normotensive pregnant plasma. No differential effect on cellular viability was found. Contrary to our hypothesis, exposure of endothelial cells to preeclamptic plasma resulted in increased nitric oxide production and nitric oxide synthase activity.