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PubMed2005

Addressing issues of maldistribution of health care workers.

INTRODUCTION: The maldistribution of health care workers is a near-universal problem, particularly in developing countries. Shortages have become most critical over the past 2 decades with both out-migration of health care workers from developing to developed countries, and intra-country disparities between urban centres and rural regions. A variety of solutions have been proposed and tried, but in recent years the problem has become increasingly serious. PROGRAMME DESCRIPTION: Over the past 15 years, we have conceptualised and implemented a programme directed at the re-supply of rural physicians to our own state, Illinois, which was recently ranked as low as sixth worse in the US with regard to physician manpower shortages in rural areas. More recently, this programme has been expanded to include other health care workers where there are equivalent shortages in health services accessibility, and the entire programme is now designated as the National Center for Rural Health Professions. PROGRAMME EVALUATION: Currently, the physician programme enjoys a 65% to 70% success rate in terms of the return of physicians to rural communities; a success largely due to the unique selection process, training, and the close relationship between students and faculty. Here, we describe this programme in detail, in the hope that elements of this somewhat unique programme may be "exportable".

Curriculum↗
PubMed1991

Effects of recombinant human granulocyte colony-stimulating factor on the mice receiving bone marrow transplantation following lethal irradiation: acceleration of recovery of the peripheral blood neutrophils and potentiation of anti-Pseudomonas resistance.

The effects of recombinant human granulocyte colony-stimulating factor (rG-CSF) on the recovery of peripheral blood neutrophil counts and resistance to i.p. infection by Pseudomonas aeruginosa were studied using a mouse bone marrow transplantation (BMT) model. A severe neutropenic period continued in the BMT mice for greater than 9 days following BMT. In contrast, the number of peripheral blood neutrophils in the BMT mice that received a daily administration of 2.5 micrograms of rG-CSF following BMT returned to normal by day 9. Thus, rG-CSF accelerated the recovery of the peripheral blood neutrophil counts in BMT mice. Anti-Pseudomonas resistance of the control BMT mice examined on days 7, 9, and 11 following BMT was one fifteenth to one fiftieth of normal mice, as indicated by the LD50 value. The anti-Pseudomonas resistance was elevated six- to sevenfold by the rG-CSF treatment. A marked increase in the neutrophils exudating into the peritoneal cavity in response to casein injection was observed in the rG-CSF-treated BMT mice. In addition, the reduced superoxide generative and phagocytic activity of the peritoneal neutrophils of the BMT mice were restored to normal by the rG-CSF treatment. It is suggested that rG-CSF potentiated anti-Pseudomonas resistance of the BMT mice by increasing neutrophils migrating to the infection site and restoring their functions; this may result from a prompt recovery of the peripheral blood neutrophil level together with the effect on neutrophil functions. These results indicate the clinical usefulness of rG-CSF in applications for BMT.

Animals↗
PubMed1994

Hepatic neutrophil sequestration in early sepsis: enhanced expression of adhesion molecules and phagocytic activity.

Abdominal sepsis was produced by cecal ligation and puncture (CLP) in rats to observe neutrophil (PMN) migration into the liver and assess the functional alteration in circulating PMNs, liver sequestered PMNs, and Kupffer cells. 7 h following CLP, rats demonstrated severe leukopenia and major amount of PMNs sequestered into the liver (17.0 +/- 5.5 x 10(6) vs. 3.1 +/- 1.6 x 10(6) in sham-operated rats, p < .01). Light microscopic evidence demonstrated the presence of such PMNs in the sinusoids and in the liver parenchyma. By 20 h following CLP, the number of PMNs in the liver was not different from sham controls. CD11b/c expression on circulating PMNs was significantly upregulated from 1.6 +/- .3 to 7.8 +/- .9 mean channel fluorescence (MCF) in 7 h CLP rats. Liver-sequestered PMNs showed further enhancement of CD11b/c expression to 10.4 +/- 1.9 MCF than the circulating PMNs. However, in the late septic rats, CD11b/c expression on circulating PMNs 2.9 +/- .5 MCF returned to the control level of 1.9 +/- .7 MCF. Liver-sequestered PMNs and Kupffer cells in septic rats exhibited remarkably enhanced phagocytic activities 53.0 +/- 10.8 and 56.9 +/- 7.7% phagocytosis, respectively, regardless of the suppression of phagocytosis in circulating PMNs (16.0 +/- 5% phagocytosis). In 7 h CLP rats, liver-sequestered PMNs exhibited a significantly higher level of superoxide anion generation 21.8 +/- 12.2 nmol/30 min/10(6) cells than did Kupffer cells (4.2 +/- 3.0 nmol/30 min/10(6) cells). These results demonstrate that the liver is a target organ for neutrophil sequestration during the septic response.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed2003

Regulation of cyclooxygenase-2 expression by iloprost in human vascular smooth muscle cells. Role of transcription factors CREB and ICER.

Prostaglandin-endoperoxide synthase-2 (PGH-synthase) or cyclooxygenase-2 (COX-2) is inducible by a variety of stimuli, e.g. inflammatory mediators, growth factors and hormones and is believed to be responsible for the majority of inflammatory prostanoid production. Moreover, it has been demonstrated that COX-2 contributes substantially to prostacyclin-synthesis in patients with atherosclerosis. In this study, we demonstrate an up-regulation of COX-2 mRNA, protein and product formation by the prostacyclin-mimetic iloprost in human vascular smooth muscle cells (hSMC). COX-2 mRNA expression was induced transiently between 1 and 6 hr and returned to basal levels after 16 hr of iloprost stimulation. COX-2 protein was induced concomitantly between 3 and 6 hr of iloprost stimulation. This was accompanied by an increase in PGI(2) formation. Forskolin, a direct activator of adenylyl cyclase, and dibutyryl cAMP, a cell-permeable cAMP analogue-induced COX-2 mRNA, suggesting a cAMP-dependent COX-2 expression in hSMC. Iloprost-induced COX-2 protein expression and PGI(2) formation was synergistically elevated by co-stimulation with the phorbolester PMA (phorbol-12-myristate-13-acetate). It is concluded, that the observed up-regulation of COX-2 with subsequent release of newly synthesized PGI(2) and the synergistic effect of iloprost and phorbolester on PGI(2) formation provide a positive feedback of prostaglandins on their own synthesizing enzyme. This might be important for control of hSMC proliferation, migration and differentiation as well as inhibition of platelet aggregation.

Cyclic AMP↗
PubMed2001

Return of potassium ion channels in regenerated hair cells: possible pathways and the role of intracellular calcium signaling.

Recent electrophysiological studies in pigeon have demonstrated that potassium channels are completely functional in regenerated type II hair cells at 21 days post-treatment (PT) with ototoxic doses of streptomycin. The currents return in the order they appear during development. The mixture of ionic currents in a regenerated type II hair cell in a particular region of the neuroepithelium is the same as in its ancestor in that region. The return of currents in regenerated type I hair cells is more complicated. The dominant conductance gKI is not present until after 70 days PT. Before 70 days, the ionic currents in type I hair cells resemble those of regenerated type II hair cells, suggesting that the ionic currents in type II hair cells might be precursors of the ionic currents in regenerated type I hair cells. New data show that at one year PT, the kinetics and drug sensitivity of the dominant K+ conductance in type I hair cells are identical to gKI. Supporting cells, believed to be the precursors of regenerated type II hair cells, have effectively no voltage-gated outward potassium channels, suggesting that regenerated type II hair cells must develop these channels de novo. The next step is to understand the mechanisms by which the potassium channel protein is synthesized, migrates through the cytosol, and is inserted into the plasmalemma of regenerating hair cells. These mechanisms are unknown. We propose that intracellular calcium is involved in this process, as well as in the differentiation, proliferation, and gene regulation of precursor cells fated to become hair cells.

Animals↗
PubMed1997

"No TEBA...forget TEBA": the plight of Malawian ex-migrant workers to South Africa, 1988-1994.

"This article is about the process of socioeconomic transformation in rural Malawi. It examines the survival strategies and enterprising spirit of Malawian migrant workers and their households. It argues that the strategies of these people often went beyond survival in the provision of basic necessities.... In March 1988, the South African Chamber of Mines stopped a century-old tradition of recruiting migrant workers from Malawi. This has arrested and put to a halt a process of accumulation taking place in the households of the returned migrant workers in the rural economy. Thus, the effects of the retrenchment of the workers will spread from the migrant and his family through the economic and social wellspring of all sectors of rural communities and their commercial lives."

Africa↗
PubMed1986

Immune complexes, serum proteins, cell-mediated immunity, and immune regulation in patients with squamous cell carcinoma of the head and neck.

A collaborative study of the humoral and cellular immune status of patients with carcinoma of the Head and Neck (H&N) was conducted at the West Virginia University (WVU) hospital. In addition, blind-coded serum panels were supplied on H&N cancer patients being treated at the National Cancer Institute (NCI). Serum protein analysis of the WVU study groups revealed that at the pretreatment sampling, the alpha-1 acid glycoprotein (AGP), total complement, and IgA levels were significantly elevated. The AGP levels and total complement levels declined to normal levels in the post-treatment period, whereas the IgA levels remained elevated throughout the entire observation period. Levels of serum immune complexes (SIC) were measured in both the WVU and NCI H&N cancer populations using the polyethylene glycol (PEG) precipitation method. In both survey populations all cancer groups had significantly elevated levels of SIC when compared to any of the control populations. The SIC levels never returned to comparative normal values even in cases after successful treatment. A subpopulation of the WVU-H&N cancer study group underwent a short course of intravenous hyperalimentation prior to their treatment regimen. These patients demonstrated a transient decrease in their SIC levels as well as a concomitant increase in their in vitro cell-mediated immune (CMI) correlates. The analysis of in vitro CMI correlates of the WVU study group using both polyclonal mitogens and specific antigens demonstrated a significant depression in these parameters pretreatment and post-treatment. In addition, it was observed that the time course for elevation of selected serum proteins (i.e., IgA and SIC) correlated with concomitant drops in CMI activity. Investigations were also conducted into the effects of immune complex-rich serum fractions upon selected in vitro CMI correlates. Significant blockage of a normal donor leukocyte migration-inhibition assay was demonstrated. Also, a similar inhibition of the ability of normal human lymphocytes to form high affinity rosettes was accomplished with serum from H&N cancer patients.

Adult↗
PubMed1998

Addition of new cells to the olfactory bulb of adult zebrafish.

We have been examining patterns of cell proliferation in the brain of adult zebrafish. Understanding this process in fish may lead to important insights due to the tremendous regenerative capabilities of these animals. Fish were exposed to a 1% solution of the thymidine analog 5-bromo-2'-deoxyuridine (BrdU) for 1 hr before being returned to small aquaria that received frequent water changes. Animals were overanesthetized and perfused with Bouin's fixative solution after two survival periods (4 hr or 3-4 weeks). Paraffin immunohistochemistry using a monoclonal antibody against BrdU was used to visualize the newly generated cells. Quantitative analyses were performed on serial, 10-micron sections from 4 animals for each survival group. Statistical determinations were based on the nonparametric Mann-Whitney U test. The average number of BrdU-labeled nuclear profiles in the bulbs, from analysis of every 5th section, was significantly different between the two groups (22.0 +/- 6.8 [SEM] for the 4-hr group and 136.7 +/- 11.3 for the 4-wk group; p < 0.05). The volumes of the bulbs, however, were not different between the two groups (p > 0.5). These data indicate that either cells divided repeatedly during the longer survival period or cells migrated into the bulb from other brain regions. To examine this phenomenon further, the location of the new cells was analyzed in three mid-bulb sections (20 microns apart) from each animal. Both the area and number of labeled nuclei in each lamina were measured to obtain an average profile density. Comparison of the 4-hr and the 4-wk groups showed that density was significantly greater in all bulb layers in the long survival group (p < 0.05 for all). In the 4-hr survival group, cells were found mainly in the olfactory nerve layer. When examined after 4 wk, proportionately more labeled cells were found in the internal cell layer. This addition of new cells could be a result of neurogenesis, gliogenesis, and/or angiogenesis. We are currently performing double-labeling experiments to determine the types of cells that are added to the adult bulb. In addition, our future plans include investigating the origin of these cells and the signals that direct their formation.

Animals↗
PubMed1994

Inhibition of retinal growth cone activity by specific metalloproteinase inhibitors in vitro.

The developing neural retina expresses a set of extracellular proteases including plasminogen activator and gelatinases. Since neurites of retina cells cultured on fluorescent gelatin digest the substrate in their paths, we have suggested that the proteases are used by the tips of growing fibers to allow them to migrate within the mass of the tissue in vivo. In order to obtain further information about relationships between extracellular proteases and fiber growth, we have examined the effects of the specific inhibitors HS-LFA (HS-Leu-Phenylala-Ala, enantiomeric forms 1 and 2), bathophenanthroline sulfonate (BPS), phenylmethyl sulfonyl fluoride (PMSF), and relevant controls on the activity of retinal growth cones in vitro, monitored by time lapse video microscopy. Of the inhibitors tested, only the two enantiomeric forms of HS-LFA caused a reproducible cessation of both spike extension and filopodial processes at the growth cone ruffling, while control media had no effect. In some cases, the growth cone swelled and exhibited small protrusions. The behavior of growth cones was in sharp distinction to that of the cytoplasm of neural cells, and membrane ruffling of flat cells, which continued in activity throughout. Growth cone activity returned after several hours in the presence of the agent. BPS was toxic at concentrations above 2.5 mM. Below that, it had no effect. L-cysteine, PMSF, and control media had no effect. The relevance of these results to the possible role of proteases in fiber outgrowth from retinal cells is discussed.

Animals↗
PubMed1999

Chemokine mRNA expression in the cauda equina of Lewis rats with experimental allergic neuritis.

Chemokines play an important role in the migration of leukocytes to inflammatory sites. In this study, using the quantitative competitive reverse transcriptase PCR method, we analyzed sequential expression of certain chemokine mRNAs in the cauda equina (CE) of rats with experimental allergic neuritis (EAN). Interferon-gamma-inducible protein (IP)-10, monocyte chemotactic protein (MCP)-1, macrophage inflammatory protein (MIP)-1alpha, the regulated upon activation normal T cell expressed and secreted chemokine (RANTES), and lymphotactin were analyzed on days 0 (pre-immunization), 7 (preclinical stage), 10 (disease onset), 13 (clinical progression), 17 (disease peak), as well as on days 20, 24, and 34 post-immunization (p.i.) (recovery). MCP-1 message increased at the preclinical stage and peaked at day 17 p.i. The increase in the early stage was not detected in other tissues, indicating peripheral nerve-specific upregulation. MIP-1alpha and IP-10 messages surged at day 13, then returned to low in the recovery stage. RANTES message increased at day 13 and peaked at day 17 p.i.; however, unlike other chemokines, it showed a second peak of expression on day 24. Lymphotactin message was undetectable at any time point. MCP-1 protein was detected immunohistologically in endothelial cells at day 7 p.i. The sequential expression of these chemokines in relation to the inflammatory process in the nerve leading to demyelination is discussed.

Animals↗
PubMed2003

Pharmacodynamics of single doses of the novel immunosuppressant FTY720 in stable renal transplant patients.

FTY720, a new and potent immunosuppressant, causes in animal models a rapid, reversible reduction of all subsets of peripheral blood lymphocytes, inducing their migration to secondary lymphoid organs. In this human phase I trial, the pharmacodynamics of single oral doses of FTY720 were evaluated. A randomized, double-blind, placebo-controlled, time-lagged study of six different single ascending oral doses of FTY720 ranging from 0.25 to 3.5 mg was conducted in stable renal transplant patients receiving a cyclosporine-based regimen. Absolute and subset lymphocyte counts, as well as absolute differential leukocyte counts, were determined by differential blood counts and flow cytometry at screening and multiple intervals thereafter. A pharmacodynamic model was established. Twenty-four single doses of FTY720 that were administered caused a transient, reversible pan-lymphopenia within 4 h. Lymphocyte subgroup analysis revealed that almost all subsets declined, with CD4- and CD45RA-positive cells being affected the most. Natural killer cells, granulocytes and monocytes were not influenced by FTY720. The lymphocyte count returned to baseline within 72 h in all dosing cohorts except the highest. Pharmacokinetik/pharmacodynamic modelling revealed a nonlinear dose effect and resulted in a good fit with observed values. These data show that FTY720 is highly effective in humans, with single oral doses of FTY720 ranging from 0.25 to 3.5 mg causing a reversible selective panlymphopenia.

Fingolimod Hydrochloride↗
PubMedDate not supplied

Can clamping of splenic vessels prevent abrupt increase of portal vein pressure and migration of transplanted hepatocytes to the liver after intrasplenic hepatocyte transplantation?

BACKGROUND/AIMS: It is well known that hepatocyte transplantation can retain some proper functions, significantly improve the survival rate of rats with different models of acute fulminant hepatic failure, correct some congenital genetic disorders, and improve liver function in cirrhosis. Portal hypertension and hepatic embolization have been described following intrasplenic hepatocyte transplantation. We evaluated the effect of temporary occlusion of splenic vessels on changes in portal vein pressure and on distribution of transplanted hepatocytes after hepatocyte transplantation into the spleen in normal rats. METHODOLOGY: Liver cirrhosis has been induced in rats by 1% dimethylnitrosamine (Sigma, St. Louis, Mo) dissolved in normal saline at the dose of 10 ml of DMN/Kg, i.p., 3 consecutive days a week for 4 weeks. Donor hepatocytes were harvested by in situ ethylenediaminetetraacetic acid (EDTA) perfusion. Changes in portal vein pressures were monitored by a pressure monitor and distribution of transplanted hepatocytes was assayed by measurement of radioactivity of 51Cr-labeled transplanted hepatocytes according to clamping or non-clamping during intrasplenic hepatocyte transplantation. RESULTS: The changes in portal pressure remained significantly high 10 min after hepatocyte transplantation in the nonocclusion groups compared to the occlusion groups. However, the changes in portal vein pressures in cirrhotic rats returned to normal faster than in normal rats after cell transplantation in the nonocclusion groups. The distribution of 51Cr-labeled transplanted hepatocytes into the spleen significantly diminished radioactivity of the liver at 10 min, 2 hours, and 24 hours in the occlusion groups compared to the nonocclusion groups. Also, duration of clamping time of splenic vessels did not influence the initial distribution of transplanted hepatocytes at the time of intrasplenic hepatocyte injection. CONCLUSIONS: These results suggested that temporary occlusion of splenic vessels should be routinely used during intrasplenic hepatocyte transplantation.

Animals↗
PubMedDate not supplied

Aetiology of endomyocardial fibrosis (EMF).

On epidemiological basis EMF behaves like a vector transmitted disease. The cardiac pathologies of EMF and HES are identical. In some cases of HES, hypereosinophilia may return to normal, leaving residual heart disease that is exactly like EMF. Most temporary residents from Europe and North America who developed EMF while resident in the endemic areas of Africa had hypereosinophilia that was induced by helminths. In our case studies from the EMF endemic areas of Nigeria, most children with acute idiopathic myocarditis associated with helminth induced hypereosinophilia, developed clinical EMF on follow up. We showed also that the rate of decline in the incidence of hypereosinophilia in EMF cases was significantly related to the duration of symptoms. Our studies and other observations show that EMF, like HES is a multiple system disease with similar organ damage. The morphologic evolution of cardiac damage in EMF appears similar to that reported for HES; with a stage of myocarditis/pericarditis, followed by a stage of cardiac necrosis, a stage of thrombosis and by the chronic fibrotic stage. Also during larval migration, all the helminths associated with EMF induce the same spectrum of damage in the central and peripheral nervous system, in the lungs, kidneys and skin, as are reported for HES. The cardiovascular damage reported for these worms (which include hypersensitivity vasculitis, acute myocarditis/ pericarditis) are also similar to what is reported for HES. Acute endomyocardial necrosis and thrombosis that are similar to what is found in HES, have been documented in Trichinella Spiralis and in filariasis. Increased cerium concentrations have been documented in the endocardium of EMF cases from South India. It remains to be established whether cerium excess, which is known to stimulate collagen synthesis does accelerate the process of endomyocardial fibrosis, following cardiac necrosis (which may have been triggered by helminths and the associated hypereosinophilia).

Animals↗
PubMed1999

Prophylactic inferior vena cava filters in trauma patients at high risk: follow-up examination and risk/benefit assessment.

PURPOSE: The efficacy of prophylactic inferior vena cava filters in selected trauma patients at high risk has come into question in relation to risk/benefit assessment. To evaluate the usefulness of prophylactic inferior vena cava filters, we reviewed our experience and overall complication rate. METHODS: From February 1991 to April 1998, the trauma registry identified 7333 admissions. One hundred eighty-seven prophylactic inferior vena cava filters were inserted. After the exclusion of 27 trauma-related deaths (none caused by thromboembolism), 160 patients were eligible for the study. The eligible patients were contacted and asked to complete a survey and return for a follow-up examination to include physical examination, Doppler scan study, vena cava duplex scanning, and fluoroscopic examination. The patients' hospital charts were reviewed in detail. The indications for prophylactic inferior vena cava filter insertion included prolonged immobilization with multiple injuries, closed head injury, pelvic fracture, spine fracture, multiple long bone fracture, and attending discretion. RESULTS: Of the 160 eligible patients, 127 were men, the mean age was 40.3 years, and the mean injury severity score was 26.1. The mean day of insertion was hospital day 6. Seventy-five patients (47%) returned for evaluation, with a mean follow-up period of 19.4 months after implantation (range, 7 to 60 months). On survey, patients had leg swelling (n = 27), lower extremity numbness (n = 14), shortness of breath (n = 9), chest pain (n = 7), and skin changes (n = 4). All the survey symptoms appeared to be attributable to patient injuries and not related to prophylactic inferior vena cava filter. Physical examination results revealed edema (n = 12) and skin changes (n = 2). Ten Doppler scan studies had results that were suggestive of venous insufficiency, nine of which had histories of deep vein thrombosis. With duplex scanning, 93% (70 of 75) of the vena cavas were visualized, and all were patent. Only 52% (39 of 75) of the prophylactic inferior vena cava filters were visualized with duplex scanning. All the prophylactic inferior vena cava filters were visualized with fluoroscopy, with no evidence of filter migration. Of the total 187 patients, 24 (12.8%) had deep vein thrombosis develop after prophylactic inferior vena cava filter insertion, including 10 of 75 (13.3%) in the follow-up group, and one patient had a nonfatal pulmonary embolism despite filter placement. Filter insertion complications occurred in 1.6% (three of 187) of patients and included one groin hematoma, one arteriovenous fistula, and one misplacement in the common iliac vein. CONCLUSION: This study's results show that prophylactic inferior vena cava filters can be placed safely with low morbidity and no attributable long-term disabilities. In this patient population with a high risk of pulmonary embolism, prophylactic inferior vena cava filters offered a 99.5% protection rate, with only one of 187 patients having a nonfatal pulmonary embolism.

Adult↗
PubMed1986

Utilization of health services by Mexican immigrant women in San Diego.

The limited empirical data available on maternal health problems among Mexican immigrant women in the United States suggest that they underutilize health services, especially general preventive care. Research conducted among legal and undocumented women in the Mexican immigrant population in San Diego, California, support these findings. Among undocumented mothers, 11.5% of their births in the U.S. occurred with no prenatal care or care sought in the third trimester, which is much higher than Mexican women legally in the country (3.6%) and the general San Diego maternal population (3.8%). When we examine births which occurred within the last five years by immigration status, we find that women legally in the country have a much higher rate of cesarean delivery of both undocumented women and women in the general San Diego maternal population. Undocumented women in our sample were much less likely than their legal counterparts to return for postpartum examinations for themselves, to seek neonatal care for their infants, and to have had Pap examinations or carry out breast self-examinations.

California↗
PubMed1996

Emergency department presentation and misdiagnosis of imported falciparum malaria.

STUDY OBJECTIVE: To review the travel history, clinical presentation, laboratory findings, diagnostic accuracy, management, and outcome of the largest reported series of emergency department patients with imported falciparum malaria in the United States. METHODS: This is a retrospective case series at large, inner-city medical center in Los Angeles. Twenty cases of falciparum malaria with initial medical evaluation in the ED were identified from the period 1979 through 1993. RESULTS: Fifteen male and 5 female patients were identified, with an age range of 5 to 55 years. All had a recent history (within 2 months) of international travel in regions endemic for malaria. Most (85%) were recent immigrants or expatriates returning from a recent visit to their native country. The most common documented symptoms were fever (100%), chills (65%), vomiting (60%), anorexia (45%), and headache (45%). Tachycardia (85%) and hyperpyrexia (> 39 degrees C) (65%) were the most common presenting signs. Malaria was considered in the ED diagnoses in only 12 cases (60%). The specification of falciparum (malignant) malaria was established in only 2 cases (10%). Hepatitis and gastroenteritis were the most common misdiagnoses. Only four patients received antimalarial medication in the ED. There were no deaths, and complications were limited to thrombocytopenia and anemia. Two patients required transfusion. CONCLUSION: Imported falciparum malaria presenting to EDs in the United States is frequently misdiagnosed. Emergency physicians improve their ability to diagnose falciparum malaria by obtaining a thorough travel history on all patients with clinical features suggesting an infectious origin and considering this diagnosis in any patient with a history of travel to or migration from malaria-endemic areas.

Adolescent↗
PubMed2002

Effects of motilin on human interdigestive gastrointestinal and gallbladder motility, and involvement of 5HT3 receptors.

A plasma motilin peak and a partial gallbladder emptying precede the antral phase III of the migrating motor complex (MMC). To clarify the causal relationship between these factors, we aimed to study the role of motilin in interdigestive gastrointestinal and gallbladder motility simultaneously. In addition, involvement of 5HT3 receptors in the action of motilin was studied. Eight fasting, healthy male volunteers received 13Leu-motilin or 0.9% NaCl i.v. for 30 min, in randomized order on two separate occasions, from 30 min after phase III. Seven of the eight subjects also received the 5HT3 receptor antagonist ondansetron in addition to motilin, on a third occasion. Antroduodenal motility, gallbladder volumes and plasma motilin were measured. The interval between the start of infusion and phase III was 95.0 (57.6-155.7) min for saline, 28.7 (21.0-33.2) min for motilin, and 39.3 (30.7-100.5) min for motilin + ondansetron (P < 0.05). Gallbladder volume decreased by one-third from 10 min after both motilin and motilin + ondansetron infusion (P < 0.05), and returned to baseline with duodenal passage of phase III. In two of the seven subjects phase III was absent after motilin + ondansetron, although gallbladder volume decreased and only refilled during a later spontaneous phase III. We conclude that motilin induces both partial gallbladder emptying and antral phase III. Indeed, although gallbladder emptying clearly precedes antral phase III, ondansetron only prevented phase III in some cases and had no effect on gallbladder emptying. Passage of phase III in the duodenum makes an important contribution to gallbladder refilling.

Adult↗
PubMed1999

Reduced cadherin/catenin complex expression in celiac disease can be reproduced in vitro by cytokine stimulation.

Celiac disease is characterized by a chronic immune response to dietary gluten, in which T cell responses result in elevated mucosal levels of tumor necrosis factor (TNF)-alpha, interleukin (IL)-1, interferon (IFN)-gamma, and transforming growth factor (TGF)-beta, which induce profound mucosal remodeling associated with increased enterocyte proliferation, apoptosis, and migration. Reduced intestinal expression of the morphoregulatory cell adhesion molecule E-cadherin, which forms complexes with beta-catenin, can increase enterocyte proliferation and migration. However, its mechanism of action in gastrointestinal inflammatory conditions and any involvement in celiac disease is unknown. In this study, we describe changes in E-cadherin and beta-catenin expression in celiac disease tissue and determine the effect of cytokines on their expression in an in vitro model. We assessed E-cadherin and beta-catenin expression in intestinal biopsies from 24 patients with celiac disease, 12 patients with treated celiac disease, and 10 healthy patients by immunohistochemistry, Western blotting, and confocal microscopy. Using Caco-2 cells, we examined the effect of TNF-alpha, IL-1, IFN-gamma, and TGF-beta on E-cadherin expression. E-cadherin transcription was assessed in both intestinal biopsies and Caco-2 cells by in situ hybridization and RT-PCR, respectively. A marked reduction in protein expression of E-cadherin and beta-catenin that returns to normal levels after treatment was observed in celiac disease; this reduction was associated with reduced levels of E-cadherin mRNA. E-cadherin expression in Caco-2 cells was significantly reduced after TNF-alpha, IL-1, and IFN-gamma stimulation. The effect of TNF-alpha on E-cadherin expression was maximal after stimulation for 48 hours and also induced modest reductions in beta-catenin expression. The action of TNF-alpha on E-cadherin was reversible and was shown to act at the transcriptional level. These results demonstrate the novel findings that E-cadherin and beta-catenin expression are reversibly down-regulated in celiac disease and that such changes in epithelial cadherin/catenin complexes may be mediated by cytokines acting on cadherin transcription.

Base Sequence↗