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Circulating levels of macrophage migration inhibitory factor are associated with mild pulmonary dysfunction after cardiopulmonary bypass.

Macrophage migration inhibitory factor (MIF) is a central mediator of inflammatory response and acute lung injury that is secreted in response to corticosteroids. A rise in systemic MIF levels was described after cardiac surgery in steroid-treated patients. This study aimed to investigate the circulating levels of MIF and the possible relationship of this cytokine to pulmonary dysfunction after cardiopulmonary bypass (CPB). We included 74 patients without previous organ dysfunction undergoing elective coronary artery bypass surgery (CABS). The same team performed all CABS via a standard technique adding methylprednisolone (15 mg/kg) to the CPB priming solution (Group MP, n = 37). In the remaining patients (Group NS, n = 37), methylprednisolone was withdrawn from the CPB priming. MIF, C-reactive protein (CRP), and total C3 were assayed in peripheral blood sampled immediately before anesthesia induction and 3, 6, and 24 h post-CPB. Preoperative risk scores and peri- and postoperative variables were documented. Postoperative kinetics of MIF and C3 were similar for both groups. Levels of CRP 24 h post-CPB were higher in Group MP (P = 0.003). Higher MIF levels were detected 6 h post-CPB, and returned to preoperative levels 24 h after CPB. MIF levels 6 h post-CPB were inversely related to the postoperative PaO2/FiO2 ratio (P = 0.0021) and were directly related to the duration of mechanical ventilation (P = 0.014). Perioperative use of methylprednisolone did not modify the MIF response to CPB, but it was related to an enhanced acute phase response. Higher circulating MIF levels 6 h post-CPB were associated with worse postoperative pulmonary short-course outcome.

Biomarkers↗

Endothelial regeneration during the repair process following Habu-snake venom induced glomerular injury.

In this study, the kinetics of glomerular endothelial cells during the repair process following glomerular injury was investigated in a model of mesangial proliferative glomerulonephritis induced by Habu-snake venom (HSV) in rats. Intravenous injection of HSV led to a cystic ballooning type lesion at day 1. Subsequently a marked segmental proliferative lesion was observed in the cystic areas at day 5. Thereafter cellularity decreased and reconstruction of the glomerular tuft was gradually observed with time. The histological structure of the glomeruli had almost returned to normal 21 days following HSV injection. After prominent depletion at day 1, the number of endothelial cells increased rapidly and reached a plateau at day 7, not significantly different from that of the control group. Morphologically endothelial cell elongation from the vascular pole into the cystic lesion was seen together with premature capillary formation in the proliferative lesion. Accompanying the reduction of mesangial expansion, the endothelial cells gradually formed definite capillary lumens. We conclude that the mesangial proliferative glomerulonephritis induced by HSV recovers to its original structural state and that the migration and proliferation of endothelial cells with accompanying capillary formation are essential for the repair process, in addition to mesangial cell proliferation.

Animals↗

Aspiration following a cave-in.

Reported is a case of massive aspiration of particulate matter after a cave-in. A 14-year-old boy was buried beneath 18 inches of dirt while playing at a construction site. After extrication he was breathing spontaneously and was transported to the emergency department on supplemental oxygen. Physical examination revealed cough, tachypnea, and diminished breath sounds of the right lung field. Chest radiographs showed multiple radiopaque densities filling the right mainstem bronchus and a left-to-right shift of the mediastinum. The patient was treated with bronchodilators followed by postural drainage and percussion. Chest radiographs and physical examination both returned to normal within 24 hours. Reports of massive aspiration of sand are scarce, and have emphasized the need for bronchoscopic removal of particles to restore ventilation. This case was managed with bronchodilators and postural drainage alone, with complete resolution of pulmonary abnormalities.

Accidents↗

Transfection of human hepatocyte growth factor gene ameliorates secondary lymphedema via promotion of lymphangiogenesis.

BACKGROUND: Lymphedema is a disorder of the lymphatic vascular system characterized by impaired lymphatic return and swelling of the extremities. Treatment for this disabling condition remains limited and largely ineffective. The goal of the present study was to investigate the therapeutic efficacy of hepatocyte growth factor (HGF) in animal models of lymphedema. METHODS AND RESULTS: Immunofluorescent analysis demonstrated that canine primary lymphatic endothelial cells (cLECs) were positive for lymphatic-specific markers (vascular endothelial growth factor receptor-3, LYVE-1, podoplanin, and Prox1) and the HGF receptor c-Met. Treating cLECs with human recombinant HGF resulted in a dose-dependent increase in cell growth and migration and increased activity of extracellular signal-regulated kinase and Akt. In human LECs, c-Met also was expressed, and treatment with HGF increased cell growth and migration in a dose-dependent manner. Transfection of human HGF plasmid DNA in cLECs also increased the c-fos promoter activity. Furthermore, weekly HGF gene transfer in a rat tail lymphedema model by disruption of lymphatic vessels resulted in a decrease in lymphedema thickness. Although expression of the endothelial cell marker PECAM-1 was increased in both HGF- and vascular endothelial growth factor 165-injected groups, expression of LEC markers (LYVE-1 and Prox1) was increased only in the HGF-injected group. CONCLUSIONS: These data demonstrate that expression of HGF via plasmid transfer improves lymphedema via promotion of lymphangiogenesis. Further studies to determine the clinical utility of this approach would be of benefit to patients with lymphedema.

Animals↗

Management of completely displaced metaphyseal fractures of the distal radius in children. A prospective, randomised controlled trial.

In a prospective, randomised controlled trial, 68 children who had a completely displaced metaphyseal fracture of the distal radius were treated either by manipulation (MUA) and application of an above-elbow cast alone or by the additional insertion of a percutaneous Kirschner (K-) wire. Full radiological follow-up to union was obtained in 65 children and 56 returned for clinical evaluation three months after injury. Maintenance of reduction was significantly better in the K-wire group and fewer follow-up radiographs were required. There was no significant difference in the clinical outcome measured three months after injury. Seven of 33 patients in the MUA group had to undergo a second procedure because of an unacceptable position compared with none of the 35 in the K-wire group (chi-squared test, p < 0.01). One patient in the K-wire group required exploration for recovery of a migrated wire. We conclude that the use of a percutaneous K-wire to augment the reduction of the fracture in children who have a completely displaced metaphyseal fracture of the distal radius is a safe and reliable way of maintaining alignment of the fracture.

Adolescent↗

Peripheral lymphocytes changes in the anamnestic response to tetanus toxoid challenge.

Few data are available on the blood lymphocyte response to revaccination in man. The anamnestic response to tetanus toxoid challenge was evaluated by a variety of techniques during the first week after revaccination. Out of twenty subjects used, eight were evaluated before and 5 days after the injections (days 1--8). Analytical cell electrophoresis showed important variation in the B and two T lymphocyte populations. The B cell percentages, assessed by EAC-rosettes and electrophoretic mobility, were found to decrease by days 2 and 3, and return to former levels by day 8, when a rise in specific antibodies was detected. A similar response was found in the T1 population generally considered to be composed of low affinity E-rosette-forming cells. Conversely, a significant increase (50--100%) in circulating T2 lymphocytes (active rosette-forming cells) was found by days 2 and 3, followed by a rapid decrease of these 'differenciated' cells. The increase in the T2 lymphocytes appeared earlier in skin test positive subjects. These changes were correlated with E-rosettes, mitogen stimulation, peripheral leucocyte migration inhibition and transformation in the presence of the antigen. EA-IgG rosettes and ADCC varied similarly. These results may indicate a significant non-specific cell mobilization following revaccination.

Antibody-Dependent Cell Cytotoxicity↗

Measurement of DNA strand breakage and DNA repair induced with hydrogen peroxide using single cell gel electrophoresis, alkaline DNA unwinding and alkaline elution of DNA.

Three techniques: single cell gel electrophoresis (SCGE), alkaline elution of DNA (AE), and alkaline DNA unwinding (ADU) were chosen to compare the sensitivity among these methods in detection of DNA damage and repair in human diploid VH10 cell line after short-term exposure to hydrogen peroxide. Using SCGE technique a dose-dependent increase in DNA migration was found in cells exposed to hydrogen peroxide in concentration range from 10 micromol/l to 100 micromol/l. Alkaline DNA unwinding method detected increased level of single strand breaks (ssb) in concentration range from 25 micromol/l to 100 micromol/l of H2O2, and alkaline elution of DNA estimated increased DNA elution rate from concentration 50 micromol/l of H2O2. In a time course study to evaluate the kinetics of DNA repair, both SCGE and ADU techniques showed that the repair of DNA strand breaks is very rapid; the level of ssb in treated cells has returned to near the background level within two hours. After this time damage remaining in the DNA was in the form of oxidised bases as revealed the incubation of treated cells with specific DNA repair endonuclease, formamidopyrimidine-DNA glycosylase.

Child↗

Gastric clearance of radiopaque markers in the evaluation of gastric emptying rate.

BACKGROUND: The study of gastric emptying rate of solids using radiopaque indigestible solid markers has been a poorly employed technique because some kinds of markers do not leave the stomach at the same time as the meal but during the interdigestive migrating motor complex (IMMC). The aim of this study was to evaluate whether markers of particular shape and size can be successfully employed for this purpose. METHODS: Twenty-eight non-ulcer dyspeptic (NUD) patients and 20 healthy volunteers received a standard solid meal (790 Kcal) together with 20 small polyethylene radiopaque cylinders (5 mm x 2 mm in diameter). Gastric emptying rate was evaluated by ultrasound while the emptying of markers was simultaneously followed by X-rays using a brilliance intensifier. RESULTS: Final emptying time (FET = time when the antrum area returns to fasting size) of digestible solids was 355+/-35 min in NUD patients versus 265+/-20 min in controls (P < 0.001). The gastric emptying curve of digestible solids correlated with emptying of markers both in NUD patients (r= +0.96) and in controls (r= +0.93). CONCLUSIONS: The assessment of gastric clearance of radiopaque cylinders of 2 mm x 5 mm in size is a reliable tool for the study of gastric emptying rate of digestible solids. This is a readily available and easily performed test in any radiology unit.

Adult↗

The transition of cells of the fission yeast beta-tubulin mutant nda3-311 as seen by freeze-substitution electron microscopy. Requirement of functional tubulin for spindle pole body duplication.

A previous fluorescence light-microscopic study showed that the fission yeast cold-sensitive beta-tubulin mutant nda3-311 was arrested with rod-like condensed chromosomes in a mitotic state at the restrictive temperature. Upon transfer to the permissive temperature, a spindle was formed and the nucleus was divided. In the present study, we employed freeze-substitution electron microscopy to examine the ultrastructure of arrested and released nda3-311 cells. In arrested cells, a single, displaced nucleus was seen with a single spindle pole body. Therefore, spindle pole body duplication seemed to require functional beta-tubulin. The nuclear membrane was highly deformed with a leaf-like profile in cross-section, possibly due to an interaction with the rod-like, condensed chromosomes. Upon transfer to the permissive temperature, the spindle pole duplicated and the daughter spindle pole bodies rapidly migrated to the opposite ends of the nucleus, accompanied by the formation of the mitotic spindle. Elongation of the nuclear envelope occurred with concomitant spindle extension, as in a wild-type mitosis. The deformed nuclear membrane became smooth and described a convex curve. The numerous vacuoles that are seen in the arrested cells decreased in number and increased in size. Septation was completed, leaving the two divided nuclei in one half of the cell. Hexagonally arranged microtubules, apparently forming the mitotic spindle, were observed in a cross-section of a cell after return to the permissive conditions.

Freezing↗

Asian-born scientists and engineers: their immigration flow and labor market adjustment.

"This paper examines the flow of Asian-born scientists and engineers and their labor market adjustment. First, main elements to affect their immigration flow are described: supply, demand, and institution....The scarcity of domestic workers is the most important factor affecting demand of immigration. Institution, such as immigration policies, is another element to influence the immigration flow....Second, by using the 1980 U.S. Census data set, their labor market adjustment is explored in terms of hourly wages. Compared to the native-born white, there is no evidence that Asian-born scientists and engineers receive lower wages or lower return on human capital."

Americas↗

Consultation-liaison psychiatry in Brazil. Psychiatric residency training.

A mailing survey assessed consultation-liaison (C-L) service delivery and training among all 23 approved psychiatric residency training programs throughout the country. Twenty questionnaires were returned. Outpatient, inpatient, emergency, and consultation services were present together in 35% of the academic hospitals where residency training took place. Consultation service was provided by 18 (90%) responding programs. Eleven of those reported C-L training as part of their general psychiatry rotation. Nevertheless, educational objectives, weekly case conferences, and didactic seminars were provided by only five of them. The training time varied from 40 to 560 hours, 190 hours on average. The same five programs offered an elective third-year residency training, including liaison with specific units. The results illustrate the migration of academic psychiatric departments from the psychiatric hospital to the general hospital as well as the beginning of C-L training programs in Brazil.

Attitude of Health Personnel↗

Acetabular revision with use of a bilobed component inserted without cement in patients who have acetabular bone-stock deficiency.

BACKGROUND: Massive deficiency of acetabular bone stock is a challenging problem in the increasing number of patients who need a revision of a failed hip arthroplasty. The bilobed cup has been presented as one alternative reconstruction technique for hips with extensive acetabular bone loss. The purpose of this study was to assess the results with use of a bilobed acetabular component inserted without cement for revision reconstruction in hips with acetabular bone deficiency in order to clarify the indications for its use and to identify the factors that influence the clinical and radiographic outcome. METHODS: Forty-one hips in thirty-eight patients had an acetabular revision with a bilobed acetabular component inserted without cement between December 1991 and December 1995. These hips were a subset of the 414 hips treated with an acetabular revision during the same period of time. One patient was lost to follow-up, and one died during the study period. Two patients who could not return for radiographic evaluation completed questionnaires. The remaining thirty-four patients (thirty-seven hips) were evaluated radiographically and clinically and were followed for an average of forty-one months (range, twenty-four to sixty-six months). RESULTS: Radiographic analysis demonstrated an improvement in the average vertical displacement of the hip center. At the time of the latest follow-up examination, 76 percent (twenty-eight) of the thirty-seven cups were stable, 8 percent (three) were probably unstable with a change in the screw position but no definite migration of the cup, and 16 percent (six) were unstable. Eight of the nine loose or probably loose components were in patients who had more than two centimeters of superior migration of the component and disruption of Kohler's line on preoperative radiographs. Additionally, implants were more likely to become unstable (demonstrating more than 4 degrees of change in the abduction angle or more than four millimeters of radiographic migration) when the inferior aspect of the component did not extend to or distal to the interteardrop line, which indicated that the component was undersized. CONCLUSIONS: On the basis of our early rate of probable or definite loosening of 24 percent (nine of thirty-seven cups) and the technical difficulties involved, we do not recommend the routine use of this component. We believe that this device is indicated when a patient has an oblong-shaped acetabular defect and the surgeon wants to correct an elevated hip center. However, the medial wall of the acetabulum (Kohler's line) should be intact if the failed component has migrated more than two centimeters. An alternative reconstruction technique, such as use of a structural allograft with or without an acetabular cage, is also an option in this situation.

Acetabulum↗

Cell proliferation and growth-associated protein 43 expression in the olfactory epithelium in Poecilia reticulata after copper solution exposure.

This study investigated the regeneration in the olfactory mucosa of the teleostean fish Poecilia reticulata when returned to dechlorinated tap water after 4-day exposure to 30 microg/L of Cu(2+). The regeneration process in the olfactory tissue was examined in fishes at 0, 3, 6 and 10 days of recovery in well water. Jade B staining permitted to evaluate the rate of the damage which was especially extended to olfactory neurons. Immediately after the end of exposure, a massive mitotic activity in the basal region of the mucosa was detected by immunostaining with PCNA. After 3 days of recovery the nuclei of the newly formed cells had already finished their migration to the upper portion of the epithelium, and cellular division was much less intense. Simultaneously, immunoreactivity for the neural growth-associated phosphoprotein GAP-43 increased respect to control levels, revealing that the new differentiating PCNA-positive elements belonged to immature neurons. After 6 days in well water no mitotic activity was detected, while the GAP-43 labelling appeared particularly concentrated in the apical surface of the olfactory epithelium. After 10 days the aspect of the olfactory epithelium was almost identical to the control. The present results suggest that after 10 days regeneration seems to be complete and integrity of the tissue restored. Furthermore, the epithelium reconstitution does not show apparent divergence from other fishes or mammals.

Animals↗

Neutrophil apoptosis in the lung after hemorrhage or endotoxemia: apoptosis and migration are independent of IL-1beta.

Hemorrhage and endotoxemia are associated with neutrophil accumulation in the lungs and the development of acute inflammatory lung injury. Because alterations in the rate of apoptosis may affect the number and function of neutrophils in the lungs, we determined the percentage of neutrophils undergoing apoptosis in the lungs of control, hemorrhaged, or endotoxemic mice. In control mice, 18.5 +/- 1.2% of pulmonary neutrophils were apoptotic. The proportion of apoptotic neutrophils in the lungs was significantly decreased 1 h after hemorrhage (6.5 +/- 1.6%, P < 0.01 compared to control) or endotoxemia (7.0 +/- 0.9%, P < 0.01 compared to control). Between 1 and 24 h after endotoxemia or hemorrhage, the proportion of apoptotic neutrophils in the lung remained significantly depressed compared to that in control, unmanipulated mice. By 48 h, the proportion of apoptotic neutrophils returned to baseline levels in the lungs of hemorrhaged (21.4 +/- 1.4%) or endotoxemic (16.4 +/- 1. 6%) mice. Lung neutrophil IL-1beta mRNA was significantly increased from that of control mice [i.e., 0.12 +/- 0.06 relative absorbance units (RAU)] 1 h after hemorrhage (5.19 +/- 0.068 RAU, P < 0.05 compared to control) or endotoxemia (8.90 +/- 1.53 RAU, P < 0.01 compared to control). In IL-1beta-deficient mice, there was no significant difference in lung neutrophil apoptosis or neutrophil entry into the lung after hemorrhage or endotoxemia compared to wild-type mice. Our results show that apoptosis among lung neutrophils is decreased for more than 24 h after hemorrhage or endotoxemia. Although IL-1beta expression is increased in lung neutrophils under these conditions, IL-1beta is not responsible for either the influx of neutrophils into the lung or the reduction of apoptosis in neutrophil populations after hemorrhage or endotoxemia.

Animals↗

Lung hyaluronan during development: a quantitative and morphological study.

Hyaluronan, an important constituent of developmental interstitium in fetal lungs, mediates cell-to-cell interactions and thereby directs migrating cells. Furthermore, because of the polyionic nature of the molecule, hyaluronan forms open, hydrated matrices that provide channels for migrating cells. This hydrated matrix undergoes contraction before birth. However, continued growth of the lung in the perinatal period requires newly synthesized hyaluronan. This study's purpose was to elucidate the changes in lung hyaluronan concentration and distribution in the perinatal period. We studied rabbits at days -6, -4, -2, -1, 0, +2, and +4 with respect to term, as well as adult rabbits. We found that hyaluronan concentration was highest in the youngest fetuses studied [682 +/- 115 micrograms/g dry wt (means +/- SD)]. However, hyaluronan concentration decreased to 129 +/- 12 micrograms/g dry wt just before birth then returned to 366 +/- 111 micrograms/g dry wt at day +4; these values were similar to adult values. We found hyaluronan staining decreased during late gestation, particularly in the interalveolar region. In the postnatal period, hyaluronan staining increased in the visceral pleura and, to a lesser extent, beneath the epithelium of the bronchioles. Hyaluronan did not reaccumulate in the interalveolar region in the postnatal period. Our data suggest a change in the predominant role of lung hyaluronan during the perinatal period. Before term, hyaluronan facilitates morphogenesis. However, hyaluronan's major role in neonatal lung is most likely in regulation of fluid balance in interstitium.

Animals↗

Leukocyte fluid shear response in the presence of glucocorticoid.

Leukocytes respond to physiological fluid shear stress ( approximately 1.5 dyn/cm(2)) by cytoplasmic reorganization. The cytoplasm is also influenced, however, by glucocorticoids. In this study, we explore how glucocorticoids may affect the leukocyte fluid shear response. Normal leukocytes, exposed to fluid shear in vitro during active migration, retract pseudopods accompanied by modestly decreasing intracellular calcium ions. In contrast, dexamethasone (DX)-treated leukocytes project pseudopods after shear exposure with a significant rise in intracellular calcium ions, an effect that can be blocked by voltage-dependent calcium channel blockers. Although a cyclic adenine monophosphate analog blocks calcium influx and pseudopod projection by DX, inhibition of A-kinase induces reversal of the shear response, as seen with DX treatment. DX also reverses the leukocyte shear response in vivo in the rat circulation. Leukocytes that adhere to the endothelium in postcapillary venules of control rats return into the circulation only after pseudopod retraction, and in DX-treated rats, adherent leukocytes return into the circulation still with projecting pseudopods. The fraction of circulating leukocytes with pseudopods in DX-treated rats is higher than in controls. Thus, the reversal of leukocyte shear response by glucocorticoids may contribute to an enhanced incidence of circulating leukocytes with pseudopods, a process that affects the kinetics of these cells in the microcirculation.

A Kinase Anchor Proteins↗

Nutritional status and mortality of refugee and resident children in a non-camp setting during conflict: follow up study in Guinea-Bissau.

OBJECTIVE: To study the effects on children of humanitarian aid agencies restricting help to refugee families (internally displaced people). DESIGN: Follow up study of 3 months. SETTING: Prabis peninsular outside Bissau, the capital of Guinea-Bissau, which has functioned as a refugee area for internally displaced people in the ongoing war, and the study area of the Bandim health project in Bissau. PARTICIPANTS: 422 children aged 9-23 months in 30 clusters. MAIN OUTCOME MEASURES: Mid-upper arm circumference and survival in relation to residence status. RESULTS: During the refugee situation all children deteriorated nutritionally, and mortality was high (3.0% in a 6 week period). Rice consumption was higher in families resident in Prabis than in refugees from Bissau but there was no difference in food expenditure. Nutritional status, measured by mid- upper arm circumference, was not associated with rice consumption levels in the family, and the decline in circumference was significantly worse for resident than for refugee children; the mid-upper arm circumference of refugee children increased faster than that of resident children. For resident children, mortality was 4.5 times higher (95% confidence interval 1.1 to 30.0) than for refugee children. Mortality for both resident and refugee children was 7.2 times higher (1.3 to 133.9) during the refugee's stay in Prabis compared with the period after the departure of the refugees. CONCLUSION: In a non-camp setting, residents may be more malnourished and have higher mortality than refugees. Major improvements in nutritional status and a reduction in mortality occurred in resident and refugee children as soon as refugees returned home despite the fact that there was no improvement in food availability.

Eating↗

Challenges in recruiting older twins for the Sri Lankan twin registry.

The National Twin Registry of Sri Lanka was established in 1997 as a volunteer register. To extend it to a population-based register, we examined the effectiveness of tracing older twins by inspecting birth records and recruiting them by postal invitation and in-person contact. Birth records at a divisional secretariat reported from 2 maternity hospitals between the years of 1954-1970 were scrutinised to identify a random sample of twins. These hospitals had the highest twin delivery rates for the whole country. We identified 620 twins and a questionnaire was mailed to them. Research assistants visited a cohort of non-respondents (71) in the postal survey. These 620 twins were identified after perusing 20700 birth records. The twinning rate was estimated at 29.95 ([620/20700] x 1000) twins per 1000 registered births (CI 27.63-32.27). In the postal survey, 37 (12%) responded and 62 letters were returned (20%). Both twins were still alive in 20 pairs, one was still alive in 15 pairs, and both twins were dead in 2 pairs. During field visits, 42 (59.2%) addresses were located. Information was available on 16 twin pairs. Both twins were alive in 8 pairs, one each in 4 pairs, and both were dead in 4 pairs and at least one twin was traced in 10 pairs (14%). Both the postal and the field survey gave a low yield. This finding is different from tracing younger twins born between 1985-1997 by using the same methods. Migration, urbanization and development in the country might have affected tracing older twins from the birth record addresses, which were decades old.

Birth Certificates↗