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Maternal influence on the use of impregnated bednets in the protection of infantile malaria.

A cross-sectional survey of 184 mothers or caretakers was undertaken to investigate the effect of socio-behavioral background on decision making in relation to the use of impregnated bednets to prevent malaria for their children in Ratchaburi Province, Thailand. It was found that most mothers had knowledge of the cause, transmission and prevention of malaria. They perceived susceptibility and severity of malaria as a risk to their children, which might even cause death. They also perceived and had positive attitudes toward impregnated bednets as a protection for their children. Three-quaters (76.4%) of them used impregnated bednets regularly to protect their children whereas one-quarter (23.6%) used infrequently and few never used. Bivariate analysis showed that the use of impregnated bednets was significantly related to the factors such as knowledge of malaria prevention, perception of benefits of the use, the receipt of information about the impregnated bednets from malaria workers.

Adult↗

Intrathecal magnesium sulfate protects the spinal cord from ischemic injury during thoracic aortic cross-clamping.

BACKGROUND: Paraplegia is a known complication after surgery on the descending thoracic aorta. Thoracic aortic cross-clamping causes an increase in proximal aortic and cerebrospinal fluid pressures. Sodium nitroprusside, though effectively decreasing proximal aortic pressure, has been implicated in worsening the incidence of paraplegia by further increasing cerebrospinal fluid pressure and decreasing distal blood pressure, thereby reducing spinal cord perfusion pressure. Intravenous administration of magnesium sulfate has been shown to offer some spinal cord protection when used with mild hypothermia. This study investigated the effect of intrathecal magnesium on the prevention of paraplegia when sodium nitroprusside is used to control proximal hypertension during thoracic aortic cross-clamping in a dog model of spinal cord ischemia. METHODS: Two groups of eight dogs underwent thoracic aortic cross-clamping via a small thoracotomy incision for 45 min. Proximal, distal, and central venous pressures and cerebrospinal fluid pressures were monitored. Temperature was maintained at 36 degrees C. Sodium nitroprusside was used to control proximal hypertension. The control group received no magnesium sulfate, and a second group received 3 mg/kg intrathecal magnesium sulfate before thoracic aortic cross-clamping. The dogs were neurologically evaluated 24 h later by an observer blinded to the dogs' group. Spinal cord segments were obtained for histologic examination. RESULTS: Proximal mean arterial pressure, cerebrospinal fluid pressure, spinal cord perfusion pressure, and central venous pressure were not statistically different between the two groups. Neurologic outcome, however, was statistically different between the groups. None of the eight dogs in the magnesium group had any measurable neurologic injury, in contrast to the control group, in which seven of the eight dogs had severe neurologic injury (P < 0.005). Post mortem histologic data supported these findings. CONCLUSIONS: Intrathecal magnesium can prevent spinal cord injury despite markedly negative spinal cord perfusion pressure during thoracic aortic cross-clamping in a canine model of spinal cord ischemia.

Animals↗

Bcl-X(L) and calyculin A prevent translocation of Bax to mitochondria during apoptosis.

During many forms of apoptosis, Bax, a pro-apoptotic protein of the Bcl-2 family, translocates from the cytosol to the mitochondria and induces cytochrome c release, followed by caspase activation and DNA degradation. Both Bcl-X(L) and the protein phosphatase inhibitor calyculin A have been shown to prevent apoptosis, and here we investigated their impact on Bax translocation. ML-1 cells incubated with either anisomycin or staurosporine exhibited Bax translocation, cytochrome c release, caspase 8 activation, and Bid cleavage; only the latter two events were caspase-dependent, confirming that they are consequences in this apoptotic pathway. Both Bcl-X(L) and calyculin A prevented Bax translocation and cytochrome c release. Bcl-X(L) is generally thought to heterodimerize with Bax to prevent cytochrome c release and yet they remain in different cellular compartments, suggesting that their heterodimerization at the mitochondria is not the primary mechanism of Bcl-X(L)-mediated protection. Using chemical cross-linking agents, Bax appeared to exist as a monomer in undamaged cells. Upon induction of apoptosis, Bax formed homo-oligomers in the mitochondrial fraction with no evidence for cross-linking to Bcl-2 or Bcl-X(L). Considering that both Bcl-X(L) and calyculin A inhibit Bax translocation, we propose that Bcl-X(L) may regulate Bax translocation through modulation of protein phosphatase or kinase signaling.

Amino Acid Chloromethyl Ketones↗

Augmentation of human influenza A virus-specific cytotoxic T lymphocyte memory by influenza vaccine and adjuvanted carriers (ISCOMS).

There is a need to improve the ability of subunit vaccines to induce CD8(+) CTL responses in humans, especially for vaccines used to prevent illness by organisms that undergo antigenic variation at their major neutralizing antibody sites, e.g., influenza A viruses and human immunodeficiency virus. Murine models have demonstrated the protective role of cross-reactive CTL against influenza A virus antigenic drift. We tested the ability of an adjuvanted carrier (Iscomatrix) to help human antigen-presenting cells present formalin-killed influenza vaccine to human CD8(+) CTL clones in vitro and in vaccinated humans. The results of a randomized, double-blind, controlled clinical study demonstrate that a single dose of a vaccine formulated into Iscom particles increased influenza A virus-specific CTL memory in 50-60% of recipients, compared to 5% of the recipients of the standard influenza vaccine.

Adolescent↗

In vivo activity of lymphocytes sensitized in vitro by antigen-fed macrophages: inhibition of lymphoma growth.

In previous studies, we have shown that macrophages fed with radiation leukemia virus could induce primary in vitro sensitization of lymphocytes which could be measured by their cytotoxic activity against target cells. In the present study, we tested the in vivo influence on tumor growth of such lymphocytes. We found that macrophage-mediated sensitized lymphocytes could protect mice against tumor growth if injected into normal recipients four days prior to challenge with lymphoma cells. The protective function of such lymphocytes was not affected by their irradiation, but no protection occurred in sublethally irradiated recipients. This indicated that the sensitized lymphocytes did not inhibit tumor cell growth directly but recruited an effector protective response in the recipient mice. This protective activity was different from the one elicited by lymphocytes which had been sensitized directly against cells carrying antigens cross-reacting with RadLV. The protective activity of the directly sensitized lymphocytes was radiosensitive and was probably mediated by their direct cytotoxic activity against tumor cells.

Animals↗

Use of mucin and hemoglobin in experimental murine gram-negative bacteremia enhances the immunoprotective action of antibodies reactive with the lipopolysaccharide core region.

An antiserum with a high content of antibodies, binding to the Gram-negative lipopolysaccharide core region, was prepared by immunizing rabbits with the rough Escherichia coli mutant J5. This antiserum was capable of protecting mice against lethal challenge doses of E. coli 0 111:B4 in a mouse model where the animals were compromised by means of mucin plus hemoglobin (LD 50 = 10(3) bacteria). However, no protection was observed in a non-compromised mouse model (LD 50 = 10(7) bacteria). This observation might explain why in the past so many discrepant results have been obtained in mouse protection studies with cross-reactive antisera.

Animals↗

Lesions of myocardial capillary vessels during open-heart surgery.

In a clinical series of patients undergoing open-heart surgery, capillary lesions in the myocardium were common when hypothermic chemical cardioplegia was used for myocardial protection during aortic cross-clamping. It seems obvious that the resulting oedematous swelling of the capillary wall, especially that of the endothelial cells, may constitute an anatomic intraluminal obstacle to myocardial reperfusion, thereby further delaying the recovery. After (mere) topical cooling, only minor capillary changes were observed. In contrast to the oedematous transformation described above for the former group, capillary endothelial cells and pericytes of the latter were diminished in cellular volume.

Capillaries↗

Metabolic effect of glucose, insulin and potassium cardioplegia.

Glucose-insulin-potassium (GIK) solution is widely used as a cardioplegic infusate for myocardial protection during aortic cross-clamping, to obtain rapid diastolic arrest and preservation of energy stores. Nine male patients with aorto-coronary bypass grafting procedure were studied with regard to the metabolic influence of GIK cardioplegia. Hyperglycemia was induced by the infusion of GIK solution for one week after surgery. The serum level of non-esterified fatty acid was high for one week while the triglyceride level was maintained at a high level only in the early post-operative period. Insulin, glucagon and growth hormone which influence carbohydrate and lipid metabolism were also elevated for one week after infusion of GIK solution. We conclude that the derangement of carbohydrate and lipid metabolism which is provoked by the use of GIK cardioplegia normalizes within two weeks after operation.

Blood Glucose↗

The cellular proliferative response, humoral antibody response, and cross reactivity studies of Tetrahymena pyriformis with Ichthyophthirius multifiliis in juvenile carp (Cyprinus carpio L.).

The immune response of 10-12-week-old juvenile carp to T. pyriformis [CCAP 1630/w, 1939 (w)] was investigated. The humoral antibody response following one and two intraperitoneal injections of whole live T. pyriformis (protein concentration of 25 micrograms/g body weight), separated by an interval of 4 weeks, was monitored over 12-16 weeks. Peak antibody titres were detected 6 weeks following antigen administration. Antibody titres were elevated following the second injection, and relatively high levels were still maintained by week 16. Proliferative responses measured by autoradiography following intraperitioneal injection of methyl 3H thymidine (1-2 microCi/g body weight) were recorded in the pronephros, opisthonephros, and spleen at weekly intervals for 4 weeks following each injection of T. pyriformis. Immunised fish had higher counts than nonimmunised controls, with the greatest counts occurring at 2 and/or 3 weeks following one injection of antigen and 2 weeks following two injections. Activity was recorded prior to peak antibody production with the pronephros and opisthonephros having greater proliferative responses than the spleen. Cross antigenicity studies to examine protection of carp against I. multifiliis following administration of T. pyriformis, showed little evidence in support of protection using this strain of T. pyriformis. Further, antisera raised in either carp, rabbits, or rats failed to show any cross antigenicity between these two species of protozoa.

Animals↗

Reactivation of Epstein-Barr virus in pregnant women: social factors, and immune competence as determinants of lymphoproliferative diseases-a hypothesis.

In normal pregnant women, reactivation of Epstein-Barr virus (EBV) frequently occurs. Cellular immune responses are apparently suppressed, but high titer EBV-specific antibodies of IgG class may compensate. The antibodies cross the placenta and protect the infant against primary infection for many months. Reactivation of EBV in pregnancy and oral excretion of virus by normal pregnant women could be one explanation why young children in large sibships (among families of low social classes) become infected early in life. Infants are likely infected by EBV from their pregnant mothers who shed virus in saliva. Moreover, the natural protection for several months in the perinatal period against Burkitt lymphoma and fatal EBV-induced lymphoproliferative diseases in congenitally immune deficient children is explained. The maturity and immunocompetence of the immune system at the time of primary infection by EBV and the size of the sibship seem to determine whether infectious mononucleosis occurs. Gammaglobulin derived from human cord blood may be a valuable source of viral-specific antibodies for serotherapy in immune deficient patients.

Adolescent↗

H19 is imprinted in the choroid plexus and leptomeninges of the mouse foetus.

It has been proposed that either the Igf-2 gene or the H19 gene--but not both--can be expressed from a given chromosome. Igf-2 is known to be biallelically expressed in the choroid plexus and leptomeninges, however, raising the question of whether H19 is down-regulated or absent there. We found by in situ hybridization that H19 is indeed expressed in the choroid plexus and leptomeninges of the developing mouse foetus. Comparison with the expression pattern of Igf-2 showed that the genes are coexpressed in all areas, with the exception of the choroid plexus epithelium. To evaluate whether H19 is also biallelically expressed in these tissues, we microdissected embryos from interspecific crosses and performed RNAse protection analysis on the isolated RNA. This revealed that H19 maintains its imprint in the choroid plexus/leptomeninges, being transcribed from the maternal allele at a level comparable to that in normal liver. We discuss the significance of these results for current models of Igf-2 and H19 imprinting.

Alleles↗

Protective effect of hyaluronidase after long-term aortic cross-clamping: initial experimental observations.

This work studies the effect of hyaluronidase on myocardium subjected to long-term aortic cross-clamping (three hours) and moderate hypothermia (28 degrees C). Animals receiving hyaluronidase (1,00o U per liter) through the root of the aorta with a procaine-potassium chloride-lasmalyte cardioplegic solution showed better functional, electrical, and morphological response than the untreated animals. These findings, although preliminary, appear to be promising for potential clinical application.

Animals↗

Loads acting in an intramedullary nail during fracture healing in the human femur.

The form and function of the musculo-skeletal system is closely related to the forces acting in its components. Significant forces are present in the long bones, but their magnitudes have so far only been estimated from mathematical models. Fracture fixation by means of metal implants provides an opportunity to measure the implant-born forces and to estimate the long bone forces before healing occurs. The load changes during fracture healing may provide additional information. Therefore, a telemetrized, interlocking femoral nail for wireless transmission of forces and moments acting across the fracture site was developed. The design was based on the geometry and material of a 16 mm AO nail with a circular, closed cross-section allowing full protection of the electronic circuits from the body fluids. After careful testing, it was implanted in a 33-year-old patient who had sustained a multifragmentary fracture of the left femur. Measurements at a rate of approx. 0.4 Hz were performed in different patient postures between the 2nd and 26th postoperative week. Significant axial forces and bending moments were measured during several activities such as sitting, unsupported leg elevation and partial weight bearing in a standing position. Forces orthogonal to the nail axis remained small. The reductions of the implant loads due to fracture consolidation were in the order of 50%. Dynamization of the nail did not change the forces. Even though the telemetry system did not allow for dynamic measurements and the results presented here provide data from one subject only, the new information will be useful with respect to implant design, biomechanics of fracture fixation and evaluation of healing progression.

Adult↗

Immunoblot analysis of cyanogen bromide-cleaved Moraxella bovis pilin reveals presence of shared antigenic determinants on pili from heterologous strains.

Moraxella bovis pilus proteins, collected and purified from four strains of M. bovis, were cleaved with cyanogen bromide. Two major fragments were produced. Antisera were produced in rabbits to the pilin protein fragments and to whole uncleaved pili from these strains. Immunoblots of whole and cyanogen bromide-cleaved pilin were reacted with the homologous and heterologous antisera to whole pili and cleaved pilin. Antisera to whole pili reacted strongly with homologous pilin. Weaker and inconsistent reactions were detected with heterologous pilin. Antisera produced to cyanogen bromide-cleaved pilin proteins reacted strongly with homologous and heterologous pilin fragments and uncleaved pilin proteins. These findings demonstrate the presence of conserved antigenic determinants on pili from heterologous strains that are non-immunogenic in the intact pilus but are immunogenic after treatment with cyanogen bromide. Cyanogen bromide-treated pilus preparation might have potential as a vaccine because antibodies are induced against heterologous strains of M. bovis, whether these cross-reactive antibodies are protective remains to be determined.

Animals↗

Right submammary minithoracotomy for repair of congenital heart defects.

OBJECTIVE: The initial experience with the right submammary minithoracotomy incision for correction of intracardiac congenital defects is reported. METHODS: Between March 1997 and March 1999, 100 children underwent repair of congenital heart disease through this approach. Their mean age and weight were 4.6 years and 20 kg, respectively. Diagnosis included: atrial septal defect (78), ventricular septal defect (7), tetralogy of Fallot (6), partial atrioventricular canal (5), double-chambered right ventricle (3) and single ventricle with dextrocardia (1). The standard technique entailed a 5 to 6 cm right submammary incision, entering the chest through the third or fourth intercostal space (depending on the body weight), direct aortic and bicaval cannulation and aortic cross-clamping with cardioplegic protection. RESULTS: There were no hospital deaths. Postoperative morbidity included bleeding in two cases, recurrent atrial septal defect in one, spleen injury in one. The average hospital stay was 3.5 days. All patient are currently free of symptoms and medications. CONCLUSIONS: (1) This approach for repair of selected congenital cardiac malformations is technically feasible, safe and effective; (2) younger age is a facilitating factor; (3) hospital stays are effectively reduced.

Adolescent↗

Surgical nurse assistants in cardiac surgery: a UK trainee's perspective.

OBJECTIVE: To assess the impact of surgical nurse assistants on surgical training based on a comparative audit of case-mix and outcome of coronary revascularizations assisted by surgical nurse assistants vs. surgical trainees. METHODS: Relevant recent articles on Calman reform of specialist training and European working time directive (EWTD) on junior doctor working hours were reviewed for the discussion. For the audit prospectively entered data of elective and expedite first time coronary artery bypass grafting cases from 2000 to 2003 were analysed. Group A (n=233, Consultant+Surgical nurse assistant), group B (n=1067, Consultant+Junior surgical trainee). Chi-square test, t-test and Fisher's test were used as appropriate for statistical analysis. RESULTS: Comparative preoperative variables were gender (P=0.8), body mass index (P=0.9), smoking (P=0.3), diabetes mellitus (P=0.2), hypertension (P=1), peripheral vascular disease (P=0.5), previous cerebrovascular accident (CVA)/transient ischemic attack (TIA) (P=0.3), renal dysfunction (P=0.4), preoperative rhythm disturbances (P=0.3), previous Q-wave myocardial infarction (MI) (P=0.4), Canadian Cardiovascular Society angina class (P=0.4), New York Heart Association heart failure class (P=0.4) and left ventricular function (P=0.4). Patients in group B were of higher risk due to age (P=0.01), coronary disease severity (P=0.05), left main stem disease (P=0.001), Parsonnet score (P=0.0001) and Euroscore (P=0.005. Regarding the myocardial protection technique, intermittent cross-clamp fibrillation was used more frequently in group A while antegrade-retrograde cold blood cardioplegia and off-pump coronary artery bypass were used more in group B (P=0.0001). The cross-clamp (P=0.0001) and operation time (P=0.0001) were significantly lower in group A despite a comparable mean number of grafts (P=0.2). There was no significant difference in the immediate postoperative outcome ventilation time (P=0.2), intensive care unit stay, postoperative stay (P=0.2), re-exploration for bleeding (P=0.5), inotrope+intra-aortic balloon pump (P=0.2), postoperative MI (P=0.9), postoperative rhythm disturbances (P=0.9), CVA/TIA (P=0.8), renal dysfunction (P=0.6), wound infection (P=0.7), sternal re-wiring (P=0.2), multi-organ failure (P=0.4) or mortality (P=0.1). CONCLUSIONS: Surgical nurse assistants can be used effectively in low-risk cases without compromising postoperative results. However, initiatives to tackle the EWTD should be focused on areas that do not compromise the training needs of junior surgical trainees. An intermediate grade between the present senior house officer and registrar grades could be a way forward.

Consultants↗

Functional recognition of 5' splice site by U4/U6.U5 tri-snRNP defines a novel ATP-dependent step in early spliceosome assembly.

A sensitive assay based on competition between cis-and trans-splicing suggested that factors in addition to U1 snRNP were important for early 5' splice site recognition. Cross-linking and physical protection experiments revealed a functionally important interaction between U4/U6.U5 tri-snRNP and the 5' splice site, which unexpectedly was not dependent upon prior binding of U2 snRNP to the branch point. The early 5' splice site/tri-snRNP interaction requires ATP, occurs in both nematode and HeLa cell extracts, and involves sequence-specific interactions between the highly conserved splicing factor Prp8 and the 5' splice site. We propose that U1 and U5 snRNPs functionally collaborate to recognize and define the 5' splice site prior to establishment of communication with the 3' splice site.

Adenosine Triphosphate↗