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Recovery of the olfactory receptor neurons in the African Tilapia mariae following exposure to low copper level.

Low levels of Cu(2+) are known to specifically cause olfactory neuron death in fish olfactory epithelium. This study investigated the morphological changes in the olfactory mucosa of the cichlid Tilapia mariae, after a 4-day exposure to different concentrations of Cu(2+) (20, 40 and 100 microg/l), and the regeneration time-frame, when fish exposed to 20 microg/l were returned to dechlorinated tap water. Light microscopy, combined with Fluoro Jade-B staining, permitted the observation of a dose-dependent damage which became less severe and more circumscribed to receptor cells when Cu(2+) concentration decreased. The regeneration process in the olfactory tissue was examined in fish after 0, 3, and 10 days of recovery in well water. Immunostaining with PCNA showed a massive mitotic activity in the basal region of the mucosa immediately after exposure was terminated. The mitotically produced elements were immature neurons since they expressed the neural growth-associated phosphoprotein GAP-43. After 3 days of recovery the nuclei had already completed their migration to the upper portion of the epithelium and mitotic activity was much less intensive. After 10 days the olfactory tissue did not present differences when compared to the control tissue. These results suggest that after 10 days the regeneration is completed and the integrity of the tissue restored.

Animals↗

Multiple sclerosis, natalizumab therapy, and progressive multifocal leukoencephalopathy.

PURPOSE OF REVIEW: Multiple sclerosis affects many people, often in early adulthood, and causes significant disability. Natalizumab is a novel agent to be evaluated for multiple sclerosis and Crohn's disease that has demonstrated unique efficacy but has unfortunately been implicated in three cases of progressive multifocal leukoencephalopathy. This review covers the mechanism of action of natalizumab and efficacy for multiple sclerosis, the three cases of natalizumab-associated progressive multifocal leukoencephalopathy, our understanding of progressive multifocal leukoencephalopathy, and the mechanisms that may account for these events. RECENT FINDINGS: Natalizumab, an anti-alpha4-integrin antibody, binds to T-cell surface receptors to prevent migration from the circulation into the brain tissue. Phase II and III trials have been completed and demonstrate previously unseen efficacy in preventing relapses and disease progression. The cases of progressive multifocal leukoencephalopathy, two fatal and one disabling, resulted in the voluntary suspension of natalizumab and bring this entire class of agents into doubt. It is important to determine what led to the development of progressive multifocal leukoencephalopathy in the natalizumab-associated cases and to advance understanding and continue to develop therapies for the treatment of multiple sclerosis. SUMMARY: With ongoing safety evaluations, natalizumab is being reevaluated by the US Food and Drug Administration for possible reapproval and return to the market. If natalizumab is reapproved, challenging questions and issues will remain in treating patients with multiple sclerosis.

Adult↗

Psychological distress through immigration: the two-phase temporal pattern?

A large community sample, cross-sectional and in part longitudinal design, and comparison groups was used to determine the timing of psychological distress among immigrants. A total of 2,378 adult immigrants from the former Soviet Union to Israel completed the self-administered questionnaire Talbieh Brief Distress Inventory. The aggregate levels of distress and six psychological symptoms--obsessiveness, hostility, interpersonal sensitivity, depression, anxiety, and paranoid ideation--were compared at 20 intervals covering 1 to 60 months after resettlement. The level of psychological distress was significantly higher in the immigrants than that of Israeli natives but not in the potential immigrant controls. A two-phase temporal pattern of development of psychological distress was revealed consisting of escalation and reduction phases. The escalation phase was characterized by an increase in distress levels until the 27th month after arrival (a peak) and the reduction phase led to a decline returning to normal levels. The 1-month prevalence rate was 15.6% for the total sample, and for highly distressed subjects it reached 24% at the 27th month after arrival, and it declined to 4% at the 44th month. The time pattern of distress shared males and females, married and divorced/widowed (but not singles), as well as subjects of all age groups (except for immigrants in their forties). The two-phase pattern of distress obtained according to cross-sectional data was indirectly confirmed through a longitudinal way. Claims of early euphoric or distress-free period followed by mental health crisis frequently referred to in the literature on migration was not supported by this study.

Adult↗

Ascorbic acid prevents corneal ulceration and perforation following experimental alkali burns.

Depressed aqueous humor glucose and ascorbic acid levels returned to control values within 14 days following a 20 sec, 6 mm. diameter, 1N sodium hydroxide burn of the rabbit cornea. These corneas did not ulcerate or perforate. After a 20 sec., 12 mm. diameter, 1N sodium hydroxide burn, aqueous humor glucose levels returned to normal values, but ascorbic acid levels remained significantly depressed for up to 30 days. These corneas became markedly ulcerated in about 60 per cent of animals and frequently perforated. Following 12 mm. alkali burns, rabbits treated daily with 1.5 Gm. of subcutaneous ascorbic acid rarely developed corneal ulcerations and the corneas did not perforate. It is suggested that exogenous maintenance of adequate aqueous humor levels of ascorbic acid overcomes the relatively scorbutic state of the anterior segment induced by a 12 mm. alkali burn, thereby impairing the development of corneal ulceration and perforation. Elevated aqueous humor levels of ascorbic acid had no influence on corneal epithelial cell migration patterns following alkali burns.

Alkalies↗

[Emergent surgery for body packing - what happens to the drugs?].

Body packing is a well recognized method of drug trafficking by smuggling drug containers in the gastrointestinal tract. Medical professionals might get involved with body packers after presentation by law enforcement or in case of medical emergencies such as drug overdose or mechanical intestinal obstruction due to the containers within the gastrointestinal tract. Besides the medical aspects in treating these patients, physicians must be aware of all the different legal specifics in dealing with body packers. In case of medical emergencies, drug traffickers have the legal status of regular patients with respect to professional medical discretion. The question remains of what physicians should do with the drugs after surgical removal? Even though the body packer remains the legal owner of the drugs, physicians may not return the drugs, since that constitutes the criminal offence of dealing in narcotics. Returning the drugs to law enforcement authorities is also prohibited because of professional medical discretion. The only way out of this predicament is for physicians to destroy the drugs under the observation of witnesses.

Abdomen, Acute↗

Size versus polarizability in protein-ligand interactions: binding of noble gases within engineered cavities in phage T4 lysozyme.

To investigate the relative importance of size and polarizability in ligand binding within proteins, we have determined the crystal structures of pseudo wild-type and cavity-containing mutant phage T4 lysozymes in the presence of argon, krypton, and xenon. These proteins provide a representative sample of predominantly apolar cavities of varying size and shape. Even though the volumes of these cavities range up to the equivalent of five xenon atoms, the noble gases bind preferentially at highly localized sites that appear to be defined by constrictions in the walls of the cavities, coupled with the relatively large radii of the noble gases. The cavities within pseudo wild-type and L121A lysozymes each bind only a single atom of noble gas, while the cavities within mutants L133A and F153A have two independent binding sites, and the L99A cavity has three interacting sites. The binding of noble gases within two double mutants was studied to characterize the additivity of binding at such sites. In general, when a cavity in a protein is created by a "large-to-small" substitution, the surrounding residues relax somewhat to reduce the volume of the cavity. The binding of xenon and, to a lesser degree, krypton and argon, tend to expand the volume of the cavity and to return it closer to what it would have been had no relaxation occurred. In nearly all cases, the extent of binding of the noble gases follows the trend xenon>krypton>argon. Pressure titrations of the L99A mutant have confirmed that the crystallographic occupancies accurately reflect fractional saturation of the binding sites. The trend in noble gas affinity can be understood in terms of the effects of size and polarizability on the intermolecular potential. The plasticity of the protein matrix permits repulsion due to increased ligand size to be more than compensated for by attraction due to increased ligand polarizability. These results have implications for the mechanism of general anesthesia, the migration of small ligands within proteins, the detection of water molecules within apolar cavities and the determination of crystallographic phases.

Amino Acid Substitution↗

Regulated expression of the ets-1 transcription factor in vascular smooth muscle cells in vivo and in vitro.

Ets-1 regulates the transcription of several genes encoding extracellular matrix proteins (ie, osteopontin and tenascin) as well as enzymes involved in degradation and remodeling of the extracellular matrix (ie, stromelysin and urokinase plasminogen activator). In the present study, we investigated the regulation of c-ets-1 in cultured rat vascular smooth muscle cells as well as in the arterial wall after balloon injury in vivo. Serum-starved smooth muscle cells exposed to serum for various time points express a major c-ets-1 mRNA transcript of 5.3 kb and minor bands of 4.0 and 2.5 kb with a peak at 2 hours after stimulation. These effects were concentration dependent. Western blotting revealed an increase in 55- and 40-kD immunoreactive ets-1 proteins in cells treated with serum for 2 hours, and binding to an oligonucleotide containing the ets-1 consensus cis-acting motif was demonstrated by electrophoretic mobility shift assay. Ets-1 mRNA abundance was induced with a peak at 2 hours after stimulation with platelet-derived growth factor-BB and with angiotensin II. There was a distinct increase of ets-1 immunoreactivity in the inner layer of the media 2 hours after balloon catheter injury of rat arteries, which declined after 6 hours and returned to the basal level 1 day after vessel wall damage. Arterial c-ets-1 mRNA content was induced with an identical time course. These findings suggest that c-ets-1 may be of importance in the mitogenic signaling pathway of smooth muscle cells grown in culture. In addition, ets-1 may play a role in the activation of smooth muscle cells in vivo after mechanical injury of the vessel wall. Because the ets-1 transcription factor activates the gene expression of a number of mRNA species involved in matrix deposition and degradation, these data are compatible with a role for ets-1 in vascular remodeling and/or cell migration.

Animals↗

Follow-up after insertion of Bird's Nest inferior vena caval filters.

OBJECTIVE: To determine the long-term clinical and radiographic outcome of patients who undergo insertion of a Gianturco-Roehm Bird's Nest vena caval filter (Cook Inc., Bloomington, Ind.). PATIENTS AND METHOD: The medical records of 40 patients who, over a 34-month period, underwent insertion of a Bird's Nest filter were reviewed and the reasons for filter insertion determined. The causes of any subsequent deaths were noted, and the autopsy findings, when available, were reviewed. Surviving patients were contacted, and 12 were willing to return for follow-up imaging, which consisted of plain radiography, real-time ultrasonography, colour Doppler imaging and contrast-enhanced computed tomography. Changes in filter position, the presence of thrombus and perforation of the vessel wall by the filter struts were documented. RESULTS: All 10 patients who underwent filter insertion while in an intensive care unit (ICU) died, an average of 22 days after the procedure. Eleven other patients also died. Recurrent pulmonary embolism was not suspected in any of these patients, and five autopsies revealed no caval thrombosis. Imaging studies in 12 of the surviving patients revealed no occlusion of the inferior vena cava and no filter migration; however, the vena caval wall was perforated in all of these patients. Nonocclusive intrafilter thrombus was detected by colour Doppler imaging in three patients. CONCLUSIONS: In this small group of patients the Bird's Nest filter was effective in preventing recurrent pulmonary embolism and caused less caval thrombosis than has previously been suspected, although intrafilter clot was found in 25% of the patients who underwent follow-up imaging. Colour Doppler imaging is the method of choice for detecting nonocclusive thrombus with this type of filter. Perforation of the caval wall was universal but not clinically symptomatic. Finally, guidelines should be established to ensure the cost-effective use of inferior vena caval filters in ICU patients.

Cause of Death↗

Long-term mental health outcome of returning migrant children and adolescents.

We examined how remigration influences the prevalence of psychiatric symptoms among children and adolescents in the long term. We investigated depressive and behavioral symptoms in 320 Finnish children and adolescents who moved back from Sweden while of school-age during the years 1984-1985 and in a series of controls. The data were gathered in two phases, with questionnaires sent to the parents, children and teachers in 1986, and with further questionnaires sent to the parents and children in 1992. Depression was measured by means of the Children's Depression Inventory (CDI) (8) and behavioral symptoms with the Children's Behavioral Questionnaire, filled in by the teachers (14) in the first phase and by the parents (15) in the second. We compared prevalence of these psychiatric symptoms between the migrants and controls in groups divided by age and sex in the two phases and examined how depressiveness or behavioral disturbance shortly after migration served to predict later psychiatric symptoms. The following findings emerged: The boys who moved before puberty had more psychiatric symptoms than their controls in both phases, while the best-adapted group consisted of the girls who moved before puberty. Those migrant children who moved during puberty had more psychiatric symptoms than their controls only in the second phase. The depressive features and behavioral disturbances observed among the migrants during the first phase did not lead to disturbances in the second phase, whereas an association was found between psychiatric disturbances among the native controls in the first and second phases.

Adaptation, Psychological↗

[Application of biliary stents in endoscopic stenting of biliary ducts].

Extra hepatic bile ducts with the gallbladder are the center place for many disease processes. In extreme cases of significant strictures of bile ducts and impairment of bile flow, obstructive jaundice occurs. There are benign and malignant biliary strictures. The treatment of obstructive jaundice depends on the removal of blockage using endoscopic and surgical methods which return the efficient bile flow to the digestive tract. The endoscopic treatment from Vater's papilla access using plastic and metal stents is the method of choice. The choice of proper prosthesis depends on the reason for biliary strictures. The plastic stents (straight, pigtail) are applied the most. Due to their low cost, easy insertion to biliary ducts and exchangeability, they are applied in benign and malignant strictures. However, metal stents (Wallstent, Diamond, Z-stent, InStent), due to the wide diameter after expansion and no possibility of removal, are applied only in malignant strictures. Endoscopic insertion of biliary endoprostheses can be burdened with complications. There have been reports of occlusion, migration with duodenal wall injury and hemorrhaging.

Bile Duct Diseases↗

Transient cellular expression of gamma-interferon in myelin-induced and T-cell line-mediated experimental autoimmune neuritis.

This study reports the cellular localization of gamma-interferon (gamma-IFN) in nerve roots during the course of experimental autoimmune neuritis induced either by active immunization (EAN) or adoptive transfer of P2-specific T-cells (AT-EAN). One micrometre thick cryosections of ventral roots of EAN and AT-EAN animals were labelled with the monoclonal antibodies DB-1 and DB-12 recognizing different epitopes of rat gamma-IFN. In EAN numerous gamma-IFN-positive cells were present before overt clinical signs and demyelination (days 11-13 after immunization). Concomitantly, raised gamma-IFN levels were measured in the serum of these animals. However, systemically increased gamma-IFN serum levels were not specific for a neuritogenic T-cell response. At subsequent stages when many axons were demyelinated (day 16 and later) gamma-IFN-positive cells had disappeared and gamma-IFN serum levels returned to normal value. gamma-Interferon positive cells could be identified as W3/13 positive T-cells and polymorphonuclear leukocytes. Additionally, a considerable number of ED1-positive macrophages showed gamma-IFN immunoreactivity. The majority of macrophages and all Schwann cells were gamma-IFN negative. Similar results were obtained in AT-EAN 4 d and 6 d following cell transfer. After nerve transection no gamma-IFN-positive cells were found in the distal stumps. The localization of gamma-IFN in nerve roots indicates an important role of this lymphokine in acute immune-mediated demyelination. gamma-Interferon most likely locally affects macrophage functions such as migration, major histocompatibility complex (MHC) class II antigen (Ia) expression, and production of cytotoxic molecules in nerves, and thereby contributes to myelin damage.

Animals↗

[Venous Doppler echography in acute pulmonary embolism].

In patients with clinically suspected pulmonary embolism, the signs and symptoms of venous thrombosis are late, insensitive and non specific. Detection of vein thrombosis requires more objective tests: (1) anatomical such as phlebography and ultrasonography which directly visualize the thrombus; the latter has the advantage of being non invasive and of providing a means to study extravascular structures as well as functional information, especially when combined with doppler velocimetry; (2) haemodynamic tests such as doppler and plethysmography which show impairment on venous return. These indirect tests are less reliable for detecting non occlusive and distal thrombi and are less specific than phlebography. Compared with phlebography, ultrasonic duplex scanning is very reliable and competitive for diagnosis and exact localization of the thrombosis, irrespective of its site (distal or proximal), its extent (isolated or extensive) and the degree of obstruction (partial or complete). However to be fully efficient, this technique must be performed by a trained specialist using specific equipment; it must always include doppler examination and explore the entire venous network. In addition, this technique makes it possible to explore the inferior and superior caval systems and the cardiac structures on the path of the migrating thrombus. Like phlebography, ultrasonography indicates venous thromboembolism only when it is positive; negative results do not exclude the diagnosis.

Acute Disease↗

Treatment of acute postoperative ileus with octreotide.

Our hypothesis was that postoperative ileus is caused by the release of neurotransmitters in the gut wall that inhibit motility. We reasoned that blocking the release with octreotide would prevent ileus. We placed serosal electrodes on the small intestine and stomachs of 15 dogs and inserted a duodenal cannula. After the animals recovered, electrical activity was recorded, and small bowel transit, colonic transit, and gastric emptying were studied radiographically and scintigraphically. Ileus was induced by celiotomy and intestinal abrasion. Dogs were randomized to receive on postoperative days 0 through 3 either a placebo (n = 5), octreotide, 1.5 micrograms/kg/8 hr subcutaneously (n = 5), or octreotide 0.83 micrograms/kg/hr intravenously (n = 5). Both doses of octreotide resulted in a faster return to preoperative values of small bowel interdigestive myoelectric activity and transit and colonic transit than did the placebo. The larger dose of octreotide, however, slowed gastric emptying. In conclusion, octreotide shortened the duration of postoperative ileus in the small bowel and colon of dogs.

Animals↗

Total lumbar disc replacement in athletes: clinical results, return to sport and athletic performance.

Despite the increasing popularity of total lumbar disc replacement (TDR) in predominantly young and active patients, no previous study has addressed possibilities, limitations and potential risks regarding athletic performance following TDR. Mechanical concerns remain and the implant's resilience as regards its load-bearing capacity during sporting activities is unknown. Thirty-nine athletic patients fulfilled the inclusion criteria for this study. These patients participated in a large variety of different types of sport. Significant and lasting pain-relief was attained following TDR with a mean follow-up of 26.3 months (range 9-50.7 months; FU rate 97.4%). Sporting activity was resumed within the first 3 months (38.5%) to 6 months (30.7%) with peak performance being reached after 5.2 months. Thirty-seven patients (94.9%) achieved resumption of sporting activity. Athletic performance improved significantly in 33 patients (84.6%). Minor subsidence was observed in 13 patients (30%) within the first 3 months with no further implant migration thereafter in 12 patients. Participation in all types of sport recorded in this study was accessible for a high rate of patients up to the level of professional athletes as well as those participating in extreme sports. Preoperative participation in sport proved to be a strong positive predictor for highly satisfactory postoperative outcome following TDR. In a selected group of patients, however, preoperative inability to participate in sporting activities did not impair postoperative physical activity. Due to the young age of the patients and significant load increase exerted during athletic activities, persisting concerns regarding the future behaviour of the implant remain and will require longer follow-up, modified investigation techniques and larger patient cohorts.

Adult↗

Risk concerns, land use, stewardship, and the Idaho National Engineering and Environmental Laboratory: attitudes of the Shoshone-Bannock and other American Indians.

This paper examines the attitudes and perceptions of 277 American Indians about hunting and fishing, risk, and future land use of the Idaho National Engineering and Environmental Laboratory (INEEL) in southeastern Idaho. Nearly half of our sample were Shoshone-Bannock tribal members living on the nearby Fort Hall Reservation, and half were American Indians from elsewhere in the western United States. We also interviewed an additional 44 White people. We examine the hypothesis that there are differences in environmental concerns and attitudes toward future land use at IN-EEL as a function of tribal affiliation (ethnicity), educational level, gender, and age. Such perceptions are important because of the existence of tribal treaties that govern the legal and cultural rights of the Shoshone-Bannock. Returning INEEL to the Shoshone-Bannock Tribes, hunting, fishing, camping, hiking, and a National Environmental Research Park ranked as the highest preferred future land uses, whereas continuing nuclear materials reprocessing and increasing the storage of nuclear wastes ranked as the lowest. There were tribal differences in land use preferences, with those of the Fort Hall Indians being more similar to those of the local Whites than to other American Indians. All groups ranked storage of nuclear material, storage of additional nuclear material, and spills and accidents as the most serious of a list of concerns provided about the site. Fort Hall Indians answered an open-ended question with concerns for population levels and migration routes of game animals and other wildlife, more than hunting and human health. The Shoshone-Bannock from Fort Hall showed an environmental sensitivity for the well-being of wildlife and the health of the ecosystem and were interested in long-term stewardship, in addition to 29 concern for human health.

Adult↗

Small bowel motility following major intra-abdominal surgery: the effects of opiates and rectal cisapride.

BACKGROUND/AIMS: Human small bowel motility is altered after laparotomy. Opiate analgesia is a possible cause of these alterations, and cisapride is a potential therapy. METHODS: Continuous proximal small bowel manometry was performed for up to 92 hours in 23 patients after major intra-abdominal surgery. They were treated with rectal cisapride (30 mg three times daily) or placebo until the clinical resolution of ileus. Small bowel manometry was performed for 30 hours in 5 volunteers receiving 1 mg/kg meperidine over 3 hours. RESULTS: Phase III activity was present within 3 hours of the end of surgery in all patients. Initially, the migrating motor complex (MMC) period was markedly reduced (mean, 22 minutes) but gradually increased. Phase II activity was absent until a median of 40 hours had elapsed. Phase III contractile amplitude was markedly attenuated in the jejunum, in contrast to that in the duodenum, presumably as a result of dilatation and/or altered tone, increasing to normal by 72 hours. In the volunteer group, although the MMC period was reduced by meperidine, it remained significantly greater than that of the placebo patient group for approximately 48 hours and phase II was reduced but not eliminated. Cisapride induced some changes in motor activity but did not accelerate the recovery of normal motility. Clinical outcome, assessed by the return of bowel sounds and passage of flatus, was accelerated by cisapride, but the trend was not significant (P = 0.11). CONCLUSIONS: This is the first published study using prolonged manometry to show the gradual evolution of small bowel motor activity after major intra-abdominal surgery. The findings suggest that surgery decreases the MMC period to the equivalent of the absolute refractory period, thereby eliminating phase II, which returns as the MMC period lengthens. Cisapride, at the dosage given, confers only modest benefit.

Abdomen↗

Direct observation and quantitative analysis of spatiotemporal dynamics of individual living monocytes during transendothelial migration.

OBJECTIVE: To visualize and quantitatively analyze spatiotemporal dynamics of individual living monocytes during transendothelial migration (TEM). METHODS AND RESULTS: We developed an in vitro new experimental system using confocal laser scanning microscope with following two improvements: (1) ultra thin collagen gel layer (30-50 microm thick) constructed under human umbilical vein endothelial cell layer for three-dimensional observation with high magnification; (2) appropriate fluorescent labeling of living monocytes and endothelial cells to keep highest cell activity. Individual monocytes behaved quite diversely. Approximately 70% of adhered monocytes directionally crawled to intercellular junction, and started invasion. Time from adhesion to start of invasion was 8.6 +/- 5.4 min (mean +/- S.D., n=61 monocytes). Approximately 80% of such invading monocytes completed TEM, but remaining 20% of once invading monocytes hesitated transmigration, and returned onto the endothelial surface. Time from start to finish of invasion was 6.3 +/- 3.2 min (mean +/- S.D., n=53 monocytes). CONCLUSIONS: Using our collagen gel-based newly-developed system, we visualized and quantitatively analyzed detailed spatiotemporal, three-dimensional dynamics of individual living monocytes during TEM. We revealed that monocytes encountered at least two hurdles, at starting invasion, and leaving endothelium, to achieve complete TEM. Approximately 56% (80% of 70% of adhered monocytes) passed both hurdles.

Cell Movement↗

Going home: giving voice to memory strategies of young Mayan refugees who returned to Guatemala as a community.

Around 1982, thousands of Guatemalan Mayas fled their villages and lands to escape the Rios Montt scorched-earth policy implemented in rural areas. After more than a decade of exile, many of those refugees have returned to their homeland. This paper looks at the ways in which young Mayan refugees who have returned home after extended exile in Mexico appropriate and distance themselves from the collective project of going home. Two Mayan communities of retornados (returnees), whose paths into exile and home again differ slightly, are compared. Outside support from international organizations and cohesion in the refugee camps enabled the young people of La Victoria to see disclosure of the traumatic past from a position of strength and confrontation as the key to social change. In La Esperanza, the past is rebuilt by the youth around avoidance of recent history, and tradition appears as a bridge between past and future. The way the youth of the two communities construct their homecoming demonstrates how small changes in the migration experience may result in considerable differences in the choice of strategies, and raises important questions about assistance programs that might be developed for these populations.

Adolescent↗