During May and June 2003, the first cluster of human monkeypox cases in the United States was reported. Most patients with this febrile vesicular rash illness presumably acquired the infection from ...prairie dogs. Monkeypox virus was demonstrated by using polymerase chain reaction in two prairie dogs in which pathologic studies showed necrotizing bronchopneumonia, conjunctivitis, and tongue ulceration. Immunohistochemical assays for orthopoxviruses demonstrated abundant viral antigens in surface epithelial cells of lesions in conjunctiva and tongue, with less amounts in adjacent macrophages, fibroblasts, and connective tissues. Viral antigens in the lung were abundant in bronchial epithelial cells, macrophages, and fibroblasts. Virus isolation and electron microscopy demonstrated active viral replication in lungs and tongue. These findings indicate that both respiratory and direct mucocutaneous exposures are potentially important routes of transmission of monkeypox virus between rodents and to humans. Prairie dogs offer insights into transmission, pathogenesis, and new vaccine and treatment trials because they are susceptible to severe monkeypox infection.
Reduced appetite and weight loss were found in clinical trials of topiramate for epilepsy. Binge-eating disorder is characterized by recurrent episodes of binge eating that are not associated with ...regular use of inappropriate compensatory behaviors. Overweight and obesity may be common complications. To explore the effectiveness and tolerability of topiramate in binge-eating disorder, we describe the response of 13 consecutive outpatients with binge-eating disorder to naturalistic, open-label treatment with topiramate.
The response of 13 female outpatients with binge-eating disorder by DSM-IV criteria to naturalistic, open-label treatment with topiramate (100-1400 mg/day) was reviewed. Response of binge-eating disorder symptoms was clinically assessed as none, mild, moderate, marked, or remission. Weight and side effects were also evaluated.
All 13 patients had comorbid Axis I psychiatric disorders along with binge-eating disorder and were receiving psychotropic medications at the time of topiramate administration. After beginning topiramate treatment, 9 patients displayed a moderate or better response of binge-eating disorder symptoms that was maintained for periods ranging from 3 to 30 months (mean +/- SD = 18.7+/-8.0 months). Two other patients displayed moderate or marked responses that subsequently diminished. The remaining 2 patients had a mild or no response. The mean +/- SD weight of the 13 patients decreased from 99.3+/-26.4 kg to 87.5+/-20.4 kg (z = -2.4, df = 1, p = .02), but only 7 patients lost > or = 5 kg of weight. The mean topiramate treatment dose was 492.3+/-467.8 mg/day for all 13 patients. The mean topiramate dose was higher in patients who lost > or = 5 kg than in patients who lost < 5 kg. Also, topiramate dose correlated significantly with weight loss (p < .01). In general, topiramate was well tolerated, with neurologic side effects the most common. Of 3 patients who discontinued topiramate because of side effects, 2 resumed the drug at a later date without significant recurrence of these effects.
Topiramate may be an effective treatment for binge-eating disorder. Controlled studies of topiramate in binge-eating disorder appear warranted.
To determine whether the introduction of an intensive care unit-based medical emergency team, responding to hospital-wide preset criteria of physiologic instability, would decrease the rate of ...predefined adverse outcomes in patients having major surgery.
Prospective, controlled before-and-after trial.
University-affiliated hospital.
Consecutive patients admitted to hospital for major surgery during a 4-month control phase and during a 4-month intervention phase.
Introduction of a hospital-wide intensive care unit-based medical emergency team to evaluate and treat in-patients deemed at risk of developing an adverse outcome by nursing, paramedical, and/or medical staff.
We measured incidence of serious adverse events, mortality after major surgery, and mean duration of hospital stay. There were 1,369 operations in 1,116 patients during the control period and 1,313 in 1,067 patients during the medical emergency team intervention period. In the control period, there were 336 adverse outcomes in 190 patients (301 outcomes/1,000 surgical admissions), which decreased to 136 in 105 patients (127 outcomes/1,000 surgical admissions) during the intervention period (relative risk reduction, 57.8%; p <.0001). These changes were due to significant decreases in the number of cases of respiratory failure (relative risk reduction, 79.1%; p <.0001), stroke (relative risk reduction, 78.2%; p =.0026), severe sepsis (relative risk reduction, 74.3%; p =.0044), and acute renal failure requiring renal replacement therapy (relative risk reduction, 88.5%; p <.0001). Emergency intensive care unit admissions were also reduced (relative risk reduction, 44.4%; p =.001). The introduction of the medical emergency team was also associated with a significant decrease in the number of postoperative deaths (relative risk reduction, 36.6%; p =.0178). Duration of hospital stay after major surgery decreased from a mean of 23.8 days to 19.8 days (p =.0092).
The introduction of an intensive care unit-based medical emergency team in a teaching hospital was associated with a reduced incidence of postoperative adverse outcomes, postoperative mortality rate, and mean duration of hospital stay.
Considerable variation in clozapine utilization exists across the United States, and little is known about the perspective of psychiatrists in states with low clozapine use. To better understand ...clozapine practices, attitudes, and barriers, a survey was administered to a group of southeastern state conference attendees (SSCA; N = 86). The same survey was administered to psychiatrists belonging to a national community psychiatry organization (AACP; N = 57), and differences were analyzed across the two samples. In comparison to the AACP, the SSCA group felt less comfortable, perceived clozapine as less safe and effective, had fewer patients on clozapine, and were more likely to prefer antipsychotic polypharmacy to clozapine use. Across the sample, use of a myocarditis screening protocol was rare (N = 14/76; 18%) and less than half used plasma antipsychotic levels to guide dosage (N = 60/129; 47%). Continuing professional education on clozapine are needed for psychiatrists who see individuals with psychotic disorders.
A novel coronavirus (CoV) has been described in association with cases of severe acute respiratory syndrome (SARS). The virus, SARS-CoV, differs from the previously described human coronaviruses, ...229E and OC43. 229E was previously shown to productively infect human monocytes/macrophages, whereas OC43 poorly infected the cells. In this study, we examined whether SARS-CoV could productively infect purified monocytes/macrophages (PM) derived from human donor cells. Unlike 229E-infected cells, which produced viral titers of 10
3.5 to 10
6
TCID
50/ml, SARS-CoV replicated poorly in PM, producing titers of 10
1.75 to 10
2
TCID
50/ml. This finding was similar to results reported for OC43-infected cells, with titers ranging from 10
1.2 to 10
2.7
TCID
50/ml. Of interest, SARS-CoV proteins were detected only in PM that did not produce significant amounts of interferon (IFN)-α, and in one such case, preliminary electron microscope studies demonstrated that SARS-CoV-like particles could enter the cells, possibly via phagocytosis. These results suggest that SARS-CoV, like human CoV OC43, poorly infects human PM, and production of IFN-α by these cells further limits the infection. Given the importance of monocytes/macrophages to the immune response, it is possible that their infection by SARS-CoV and alteration of this infection by IFN-α may be important to the course of the infection in humans.
Protein interactions between MAP kinases and substrates, activators, and scaffolding proteins are regulated by docking site motifs, one containing basic residues proximal to Leu-X-Leu (DEJL) and a ...second containing Phe-X-Phe (DEF). Hydrogen exchange mass spectrometry was used to identify regions in MAP kinases protected from solvent by docking motif interactions. Protection by DEJL peptide binding was observed in loops spanning β7-β8 and αD-αE in p38α and ERK2. In contrast, protection by DEF binding to ERK2 revealed a distinct hydrophobic pocket for Phe-X-Phe binding formed between the P+1 site, αF helix, and the MAP kinase insert. In inactive ERK2, this pocket is occluded by intramolecular interactions with residues in the activation lip. In vitro assays confirm the dependence of Elk1 and nucleoporin binding on ERK2 phosphorylation, and provide a structural basis for preferential involvement of active ERK in substrate binding and nuclear pore protein interactions.
Rehabilitation increasingly addresses the International Classification of Functioning, Disability and Health's (ICF) concepts of activity and participation, but little is known about associations ...between changes in body functions and structures, activity, and participation. We conducted a before‐and‐after study of 35 ambulatory children with spastic diplegia or hemiplegic cerebral palsy, mean age 5 years 6 months (SD 2y 2mo). Children were in Gross Motor Function Classification System (GMFCS) Levels I (n=11), II (n=12), or III (n=12). We assessed body functions and structures, activity, and participation at baseline and at 2 months and 6 months post‐botulinum toxin type A (BoNT‐A) injection. Repeated‐measures analysis of variance evaluated change, and linear regression assessed relationships. Baseline score relationships were moderate to strong but, despite similar directions of change at 2 months, change score relationships between measures of body functions and structures (spasticity and timed walk), activity (Gross Motor Function Measure and Pediatric Evaluation of Disability Inventory), and participation (Pediatric Outcomes Data Collection Instrument) at 2 months and 6 months were poor to fair (r<0.40). Predictor combinations accounted for <69% of variation in activity and participation change scores. Predictors often pertained to baseline score, GMFCS level, or age. Relationships between changes at different ICF levels are complex, and activity and participation gains post‐BoNT‐A are likely to be influenced by the child and environment factors.
Prior research has shown that neighbourhood racial and income contexts remain similar across generations within White, Black and Latino families in the US. This article builds on this research by ...examining the extent to which geographical mobility during the transition to adulthood attenuates the perpetuation of residential segregation from Whites among Asians, Blacks and Latinos. Data from the National Education Longitudinal Study linked to 1990 and 2000 US census data were analysed. Results suggest that residential exposure to Whites is similar during youth and adulthood among young adults who live in the same metropolitan area where they lived as adolescents, regardless of race/ethnicity. Among those who migrate to another metropolitan area, adolescent exposure predicts exposure among Asian, Black and Latino young adults, but not among Whites themselves. Thus, limited experience with integrated neighbourhoods during adolescence among non-Whites and limited geographical mobility among all young adults help to perpetuate segregation.
The overproduction of reactive oxygen species has been linked to a wide array of health disorders. The ability to noninvasively monitor oxidative stress in vivo could provide substantial insight into ...the progression of these conditions and, in turn, could facilitate the development of better diagnosis and treatment options. A mononuclear Mn(II) complex with the redox-active ligand N,N′-bis(2,5-dihydroxybenzyl)-N,N′-bis(2-pyridinylmethyl)-1,2-ethanediamine (H4qtp2) was made and characterized. A previously prepared Mn(II) complex with a ligand containing a single quinol subunit was found to display a modest T 1-derived relaxivity response to H2O2. The introduction of a second redox-active quinol both substantially improves the relaxivity response of the complex to H2O2 and reduces the cytotoxicity of the sensor but renders the complex more susceptible to transmetalation. The addition of H2O2 partially oxidizes the quinol subunits to para-quinones, concomitantly increasing the r 1 from 5.46 mM–1 s–1 to 7.17 mM–1 s–1. The oxidation of the ligand enables more water molecules to coordinate to the metal ion, providing an explanation for the enhanced relaxivity. That the diquinol complex is only partially oxidized by H2O2 is attributed to its activity as an antioxidant; the complex can both catalytically degrade superoxide and serve as a hydrogen atom donor.
“Kangaroo mother care” was first described as an alternative method of caring for low birth weight infants in resource-limited countries, where neonatal mortality and infection rates are high because ...of overcrowded nurseries, inadequate staffing, and lack of equipment. Intermittent skin-to-skin care (SSC), a modified version of kangaroo mother care, is now being offered in resource-rich countries to infants needing neonatal intensive care, including those who require ventilator support or are extremely premature. SSC significantly improves milk production by the mother and is associated with a longer duration of breastfeeding. Increased parent satisfaction, better sleep organization, a longer duration of quiet sleep, and decreased pain perception during procedures have also been reported in association with SSC. Despite apparent physiologic stability during SSC, it is prudent that infants in the NICU have continuous cardiovascular monitoring and that care be taken to verify correct head positioning for airway patency as well as the stability of the endotracheal tube, arterial and venous access devices, and other life support equipment.
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