Retrospective observational study of patient outcomes with local wound infusion vs epidural analgesia after open hepato-pancreato-biliary surgery.

BACKGROUND: Epidural analgesia is conventionally used as the mainstay of analgesia in open abdominal surgery but has a small life-changing risk of complications (epidural abscesses or haematomas). Local wound-infusion could be a viable alternative and are associated with fewer adverse effects. METHODS: A retrospective observational analysis of individuals undergoing open hepato-pancreato-biliary surgery over 1 year was undertaken. Patients either received epidural analgesia (EP) or continuous wound infusion (WI) + IV patient controlled anaesthesisa (PCA) with an intraoperative spinal opiate. Outcomes analyzed included length of stay, commencement of oral diet and opioid use. RESULTS: Between Jan 2016- Dec 2016, 110 patients were analyzed (WI n=35, EP n=75). The median length of stay (days) was 8 in both the WI and EP group (p=0.846), the median time to commencing oral diet (days) was 3 in WI group and 2 in EP group (p=0.455). There was no significant difference in the amount of oromorph, codeine or tramadol (mg) between WI and EP groups (p=0.829, p=0.531, p=0.073, respectively). CONCLUSIONS: Continuous wound infusion + IV PCA provided adequate analgesia to patients undergoing open hepato-pancreato-biliary surgery. It was non-inferior to epidural analgesia with respect to hospital stay, commencement of oral diet and opioid use.

Trichosporon fungemia in a pediatric patient with acute lymphoblastic leukemia.

Trichosporon fungemia is a life-threatening opportunistic infection that is increasing in frequency. Invasive disease occurs almost exclusively in immunocompromised hosts, particularly in neutropenic adults with hematological malignancies and uncommonly in children. We report the case of a pediatric patient where disseminated trichosporonosis progressed while on micafungin, between treatments with voriconazole and amphotericin B, demonstrating the difficulty with and importance of prolonged and continuous treatment.

Acute mercury toxicity modulates cytochrome P450, soluble epoxide hydrolase and their associated arachidonic acid metabolites in C57Bl/6 mouse heart.

Mercury exposure is associated with increased risk of cardiovascular disease and profound cardiotoxicity. However, the correlation between Hg(2+)-mediated toxicity and alteration in cardiac cytochrome P450s (Cyp) and their dependent arachidonic acid metabolites has never been investigated. Therefore, we investigated the effect of acute mercury toxicity on the expression of Cyp-epoxygenases and Cyp-ω-hydroxylases and their associated arachidonic acid metabolites in mice hearts. In addition, we examined the expression and activity of soluble epoxide hydrolase (sEH) as a key player in arachidonic acid metabolism pathway. Mercury toxicity was induced by a single intraperitoneal injection (IP) of 2.5 mg/kg of mercuric chloride (HgCl2). Our results showed that mercury treatment caused a significant induction of the cardiac hypertrophy markers, atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP); in addition to Cyp1a1, Cyp1b1, Cyp2b9, Cyp2b10, Cyp2b19, Cyp2c29, Cyp2c38, Cyp4a10, Cyp4a12, Cyp4a14, Cyp4f13, Cyp4f15, Cyp4f16 and Cyp4f18 gene expression. Moreover, Hg(2+) significantly increased sEH protein expression and activity levels in hearts of mercury-treated mice, with a consequent decrease in 14,15-, and 11,12-epoxyeicosatrienoic acids (EETs) levels. Whereas the formation of 14,15-, 11,12-, 8,9-dihydroxyeicosatrienoic acids (DHETs) was significantly increased. In conclusion, acute Hg(2+) toxicity modulates the expression of several Cyp and sEH enzymes with a consequent decrease in the cardioprotective EETs which could represent a novel mechanism by which mercury causes progressive cardiotoxicity. Furthermore, inhibiting sEH might represent a novel therapeutic approach to prevent Hg(2+)-induced hypertrophy.

Posttranslational mechanisms modulating the expression of the cytochrome P450 1A1 gene by methylmercury in HepG2 cells: a role of heme oxygenase-1.

Recently we demonstrated the ability of mercuric chloride (Hg(2+)) in human hepatoma HepG2 cells to significantly decrease the TCDD-mediated induction of Cytochrome P450 1A1 (CYP1A1) mRNA, protein, and catalytic activity levels. In this study we investigated the effect of methylmercury (MeHg) on CYP1A1 in HepG2 cells. For this purpose, cells were co-exposed to MeHg and TCDD and the expression of CYP1A1 mRNA, protein, and catalytic activity levels were determined. Our results showed that MeHg did not alter the TCDD-mediated induction of CYP1A1 mRNA, or protein levels; however it was able to significantly decrease CYP1A1 catalytic activity levels in a concentration-dependent manner. Importantly, this inhibition was specific to CYP1A1and was not radiated to other aryl hydrocarbon receptor (AhR)-regulated genes, as MeHg induced NAD(P)H:quinone oxidoreductase 1 mRNA and protein levels. Mechanistically, the inhibitory effect of MeHg on the induction of CYP1A1 coincided with an increase in heme oxygenase-1 (HO-1) mRNA levels. Furthermore, the inhibition of HO-1 activity, by tin mesoporphyrin, caused a complete restoration of MeHg-mediated inhibition of CYP1A1 activity, induced by TCDD. In addition, transfection of HepG2 cells with siRNA targeting the human HO-1 gene reversed the MeHg-mediated inhibition of TCDD-induced CYP1A1. In conclusion, this study demonstrated that MeHg inhibited the TCDD-mediated induction of CYP1A1 through a posttranslational mechanism and confirms the role of HO-1 in a MeHg-mediated effect.

Differential modulation of cytochrome P450 1a1 by arsenite in vivo and in vitro in C57BL/6 mice.

Heavy metals, typified by arsenite (As(III)), have been implicated in altering the carcinogenicity of aryl hydrocarbon receptor (AhR) ligands, typified by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), by modulating the induction of the Cyp1a1 enzyme, but the mechanism remains unresolved. In this study, the effects of As(III) on Cyp1a1 expression and activity were investigated in C57BL/6 mouse livers and isolated hepatocytes. For this purpose, C57BL/6 mice were injected intraperitoneally with As(III) (12.5 mg/kg) in the absence and presence of TCDD (15 µg/kg) for 6 and 24 h. Furthermore, isolated hepatocytes from C57BL/6 mice were treated with As(III) (1, 5, and 10 µM) in the absence and presence of TCDD (1 nM) for 3, 6, 12, and 24 h. At the in vivo level, As(III) decreased the TCDD-mediated induction of Cyp1a1 mRNA at 6h while potentiating its mRNA, protein, and catalytic activity levels at 24 h. At the in vitro level, As(III) decreased the TCDD-mediated induction of Cyp1a1 mRNA in a concentration- and time-dependent manner. Moreover, As(III) decreased the TCDD-mediated induction of Cyp1a1 protein and catalytic activity levels at 24 h. Interestingly, As(III) increased the serum hemoglobin (Hb) levels in animals treated for 24 h. Upon treatment of isolated hepatocytes with Hb alone, there was an increase in the nuclear accumulation of AhR and AhR-dependent luciferase activity. Furthermore, Hb potentiated the TCDD-induced AhR-dependent luciferase activity. Importantly, when isolated hepatocytes were treated for 5h with As(III) in the presence of TCDD and the medium was then replaced with new medium containing Hb, there was potentiation of the TCDD-mediated effect. Taken together, these results demonstrate for the first time that there is a differential modulation of the TCDD-mediated induction of Cyp1a1 by As(III) in C57BL/6 mouse livers and isolated hepatocytes. Thus, this study implicates Hb as an in vivo-specific modulator.

Modulation of cytochrome P450 1 (Cyp1) by vanadium in hepatic tissue and isolated hepatocyte of C57BL/6 mice.

The objective of the current study was to investigate the effect of vanadium (V(5+)) on Cyp1 expression and activity in C57BL/6 mice liver and isolated hepatocytes. For this purpose, C57BL6 mice were injected intraperitoneally with V(5+) (5 mg/kg) in the absence and presence of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) (15 µg/kg) for 6 and 24 h. Furthermore, isolated hepatocytes from C57BL6 mice were treated with V(5+) (5, 10, and 20 µM) in the absence and presence of TCDD (1 nM) for 3, 6, 12, and 24 h. In vivo, V(5+) alone did not significantly alter Cyp1a1, Cyp1a2, or Cyp1b1 mRNA, protein, or catalytic activity levels. Upon co-exposure to V(5+) and TCDD, V(5+) significantly potentiated the TCDD-mediated induction of the Cyp1a1, Cyp1a2, and Cyp1b1 mRNA, protein, and catalytic activity levels at 24 h. In vitro, V(5+) decreased the TCDD-mediated induction of Cyp1a1 mRNA, protein, and catalytic activity levels. Furthermore, V(5+) significantly inhibited the TCDD-induced AhR-dependent luciferase activity. V(5+) also increased serum hemoglobin (Hb) levels in animals treated for 24 h. Upon treatment of isolated hepatocytes with Hb alone or in the presence of TCDD, there was an increase in the AhR-dependent luciferase activity. When isolated hepatocytes were treated for 2 h with V(5+) in the presence of TCDD, followed by replacement of the medium with new medium containing Hb, there was further potentiation to the TCDD-mediated effect. The present study demonstrates that there is a differential modulation of Cyp1a1 by V(5+) in C57BL/6 mice livers and isolated hepatocytes and demonstrates Hb as an in vivo specific modulator.

Modulation of aryl hydrocarbon receptor-regulated genes by acute administration of ammonium metavanadate in kidney, lung and heart of C57BL/6 mice.

We recently reported that vanadium (V(5+) ) was able to decrease the 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-mediated induction of Cyp1a1 and Nqo1 at mRNA, protein and catalytic activity levels in mouse hepatoma Hepa 1c1c7 and human hepatoma HepG2 cells. However, little is known regarding the in vivo effects. Thus, the objective of this study was to investigate whether similar effects would occur at the in vivo level. Therefore, we examined the effect of exposure to V(5+) (5 mg kg(-1) ) with or without TCDD (15 µg kg(-1) ) on the AhR-regulated genes in kidney, lung and heart of C57BL/6 J mice. Our results demonstrated that V(5+) alone significantly decreased Cyp1b1 protein and catalytic activity levels in kidney at 24 h. Moreover, it significantly potentiated Nqo1 and Gsta1 gene expression in the heart, and only Gsta1 gene expression in the lung. Upon co-exposure, we found that V(5+) significantly inhibited the TCDD-mediated induction of Cyp1a1, Cyp1a2 and Cyp1b1 mRNA, protein and catalytic activity levels in the kidney at 24 h. On the other hand, V(5+) significantly potentiated the TCDD-mediated induction of Nqo1 and Gsta1 protein and activity levels in the kidney. Cyp1a1, Cyp1b1, Nqo1 mRNA, protein and catalytic activity levels in the lung were significantly potentiated at 6 h. Interestingly, all tested genes in the heart were significantly decreased at 6 h with the exception of Gsta1 mRNA. The present study demonstrates that V(5+) modulates TCDD-induced AhR-regulated genes. Furthermore, the effect on one of these enzymes could not be generalized to other enzymes even if it was in the same organ.

Mercury modulates the cytochrome P450 1a1, 1a2 and 1b1 in C57BL/6J mice: in vivo and in vitro studies.

In the current study C57BL/6J mice were injected intraperitoneally with Hg(2+) in the absence and presence of TCDD. After 6 and 24h the liver was harvested and the expression of Cyps was determined. In vitro, isolated hepatocytes were incubated with TCDD in the presence and absence of Hg(2+). At the in vivo level, Hg(2+) significantly decreased the TCDD-mediated induction of Cyps at 6h while potentiating their levels at 24h. In vitro, Hg(2+) significantly inhibited the TCDD-mediated induction of Cyp1a1 in a concentration- and time-dependent manner. Interestingly, Hg(2+) increased the serum hemoglobin (Hb) levels in mice treated for 24h. Upon treatment of isolated hepatocytes with Hb alone, there was an increase in the AhR-dependent luciferase activity with a subsequent increase in Cyp1a1 protein and catalytic activity levels. Importantly, when hepatocytes were treated for 2h with Hg(2+) in the presence of TCDD, then the medium was replaced with new medium containing Hb, there was potentiation of the TCDD-mediated effect. In addition, Hg(2+) increased heme oxygenase-1 (HO-1) mRNA, which coincided with a decrease in the Cyp1a1 activity level. When the competitive HO-1 inhibitor, tin mesoporphyrin was applied to the hepatocytes there was a partial restoration of Hg(2+)-mediated inhibition of Cyp1a1 activity. In conclusion, we demonstrate for the first time that there is a differential modulation of the TCDD-mediated induction of Cyp1a1 by Hg(2+) in C57BL/6J mice livers and isolated hepatocytes. Moreover, this study implicates Hb as an in vivo specific modulator of Cyp1 family.

Effect of mercury on aryl hydrocarbon receptor-regulated genes in the extrahepatic tissues of C57BL/6 mice.

The individual toxic effects of aryl hydrocarbon receptors (AhR) ligands such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) or heavy metals typified by mercury (Hg(2+)) has been previously demonstrated. However, little is known about the combined toxic effects of TCDD and Hg(2+)in vivo. Therefore, we examined the effect of exposure to Hg(2+) (2.5mg/kg) in the absence and presence of TCDD (15 µg/kg) on the AhR-regulated genes using C57Bl/6 mice. Hg(2+) alone did not affect kidney, lung, or heart Cyp1a1/1a2/1b1 mRNA levels. On the contrary, Hg(2+) alone significantly induced kidney Cyp1a1/1a2/1b1 and lung Cyp1b1 protein and catalytic activities. Hg(2+) also induced Nqo1, Gsta1, and HO-1 at the mRNA, protein, and activity levels in the kidney and heart but not in the lung. Upon co-exposure to Hg(2+) and TCDD, Hg(2+) significantly potentiated the TCDD-mediated induction of kidney and lung Cyp1a1/1a2/1b1 mRNA levels, while it decreased their kidney protein and catalytic activity and it increased their lung protein. In addition, Hg(2+) potentiated the TCDD-mediated induction of Nqo1, Gsta1, and HO-1 at mRNA, protein and activity levels in all tissues. The present study demonstrates that Hg(2+) modulates the constitutive and TCDD-induced AhR-regulated genes in a time-, tissue- and, AhR-regulated enzyme genes manner.

Differential modulation of aryl hydrocarbon receptor regulated enzymes by arsenite in the kidney, lung, and heart of C57BL/6 mice.

During the last couple of decades, efforts have been made to study the toxic effects of individual aryl hydrocarbon receptors (AhR) ligands such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) or heavy metals typified by arsenic As(III). However, little is known about the combined toxic effects of TCDD and As(III) in vivo. Previous reports from our laboratory and others have demonstrated that As(III), by itself or in the presence of AhR ligands, such as TCDD, is capable of differentially altering the expression of various phase I and phase II AhR-regulated genes in in vitro systems. Thus, the objective of the current study was to investigate whether or not similar effects would occur at the in vivo level. Therefore, we examined the effect of exposure to As(III) (12.5 mg/kg) in the absence and presence of TCDD (15 µg/kg) on the AhR-regulated genes using C57Bl/6 mice. Our results demonstrated that As(III) alone inhibited Cyp1a1 and Cyp1a2 in the kidney, while it induced their levels in the lung and did not affect their mRNA levels in the heart. As(III) also induced Nqo1 and Gsta1 in all tested tissues. Upon co-exposure to As(III) and TCDD, As(III) inhibited the TCDD-mediated induction of Cyp1a1 in the kidney and heart, Cyp1a2 in the kidney and heart, while it potentiated TCDD-mediated induction of Cyp1a1 in the lung, and Nqo1 and Gsta1 in the kidney and lung. In conclusion, the present study demonstrates for the first time that As(III) modulates constitutive and TCDD-induced AhR-regulated genes in a time-, tissue-, and AhR-regulated enzyme-specific manner.

Transcriptional modulation of the NAD(P)H:quinone oxidoreductase 1 by mercury in human hepatoma HepG2 cells.

NAD(P)H:quinone oxidoreductase (NQO1)-mediated detoxification of quinones plays a critical role in cancer prevention. Heavy metals such as mercury (Hg(2+)) alter the carcinogenicity of aryl hydrocarbon receptor ligands, mainly by modifying various xenobiotic-metabolizing enzymes such as NQO1. Therefore, we examined the effect of Hg(2+) on the expression of NQO1 in human hepatoma HepG2 cells. For this purpose HepG2 cells were incubated with various concentrations of Hg(2+) (2.5, 5, and 10µM) in the presence and absence of two NQO1 inducers, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and isothiocyanate sulforaphane (SUL), as bifunctional and monofunctional inducers, respectively. Analysis of the time-dependent effect of Hg(2+) revealed that Hg(2+) increased the expression of NQO1 mRNA in a time-dependent manner. In addition, Hg(2+) increased NQO1 at the mRNA, protein, and activity levels in the presence and absence of both NQO1 inducers, TCDD and SUL, which coincided with increased nuclear accumulation of Nrf2 protein. Investigating the effect of Hg(2+) at the transcriptional level revealed that Hg(2+) significantly induced the antioxidant-responsive element-dependent luciferase reporter gene expression in the absence and the presence of both NQO1 inducers. NQO1 mRNA and protein decay experiments revealed a lack of posttranscriptional and posttranslational mechanisms. Transfecting HepG2 cells with siRNA for Nrf2 significantly decreased the Hg(2+)-mediated induction of NQO1 mRNA and catalytic activity by approximately 90%. In conclusion, we demonstrated that Hg(2+) regulates the expression of the NQO1 gene through a transcriptional mechanism in human hepatoma HepG2 cells. In addition, Nrf2 is involved in the modulation of NQO1 by Hg(2+).

Mercury modulates the CYP1A1 at transcriptional and posttranslational levels in human hepatoma HepG2 cells.

Aryl hydrocarbon receptor (AhR) ligands such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and metals, such as mercury (Hg(2+)), are environmental co-contaminants and their molecular interaction may disrupt the coordinated regulation of the carcinogen-activating enzyme cytochrome P450 1A1 (CYP1A1). Therefore, we examined the effect of co-exposure to Hg(2+) and TCDD on the expression of the CYP1A1 in HepG2 cells. Our results showed that Hg(2+) significantly inhibited the TCDD-mediated induction of CYP1A1 at the mRNA, protein, and catalytic activity levels. At the transcriptional level, co-exposure to Hg(2+) and TCDD significantly decreased the TCDD-mediated induction of AhR-dependent luciferase reporter gene expression. Moreover, Hg(2+) did not affect CYP1A1 mRNA stability, while decreasing its protein half-life, suggesting the involvement of a posttranslational mechanism. Importantly, Hg(2+) increased the expression of heme oxygenase-1 (HO-1), a rate limiting enzyme in heme degradation, which coincided with further decrease in the CYP1A1 catalytic activity levels. Upon using a competitive HO-1 inhibitor, tin mesoporphyrin, heme precursor, hemin, or transfecting the HepG2 cells with siRNA for HO-1 there was a partial restoration of the inhibition of TCDD-mediated induction of CYP1A1 catalytic activity. In conclusion, we demonstrate that Hg(2+) down-regulates the expression of CYP1A1 at the transcriptional and posttranslational levels in HepG2 cells. In addition, HO-1 is involved in the modulation of CYP1A1 at the posttranslational level.

One-year outcomes and health care utilization in survivors of severe acute respiratory syndrome.

BACKGROUND: Severe Acute Respiratory Syndrome (SARS) became a global epidemic in 2003. Comprehensive information on 1-year outcomes and health care utilization is lacking. Research conducted during the SARS outbreak may help inform research planning for future public health emergencies. The objective of this study was to evaluate the 1-year outcomes in survivors of SARS and their family caregivers. METHOD: The study was prospective and observational. We evaluated 117 SARS survivors from Toronto, Ontario. Patients were interviewed and underwent physical examination, pulmonary function testing, chest radiography, a 6-minute-walk test, quality-of-life measures, and self-report of health care utilization. At 1 year, informal caregivers were identified for a survey on caregiver burden. RESULTS: The enrolled survivors of SARS were young (median age, 42 years), and most were women (67%) and health care workers (65%). At 1 year after hospital discharge, pulmonary function measures were in the normal range, but 18% of patients had a significant reduction in distance walked in 6 minutes. The Medical Outcomes Study 36-Item Short Form Health Survey (SF-36) domains were 0.3 to 1.0 SD below normal at 1 year. Of the patients, 17% had not returned to work by 1 year. Fifty-one patients required 668 visits to psychiatry or psychology practitioners. During the SARS epidemic, informal caregivers reported a decline of 1.6 SD below normal on the mental component score of the SF-36. CONCLUSIONS: Most SARS survivors had good physical recovery from their illness, but some patients and their caregivers reported a significant reduction in mental health 1 year later. Strategies to ameliorate the psychological burden of an epidemic on the patient and family caregiver should be considered as part of future pandemic planning.

Stronger nasal responsiveness to cold air in individuals with rhinitis and asthma, compared with rhinitis alone.

BACKGROUND: We have previously proposed that, compared with rhinitis alone, the constellation of upper and lower airway allergic disease is a manifestation of a more severe form of a syndrome affecting the entire airway. If this is correct, not only the lower, but also the upper airways of patients with asthma and rhinitis should demonstrate more abnormalities compared with patients with rhinitis alone, including higher sensitivity to irritant factors. Objective To test the hypothesis that, a previously well-studied natural nasal stimulus, cold, dry air (CDA), produces a stronger response in subjects with allergic rhinitis (AR) and asthma compared with subjects with AR alone. METHODS: We performed nasal provocation with CDA on 24 individuals with asthma and rhinitis and 17 with rhinitis alone. Prior to and after the challenge, nasal symptoms were recorded using visual analogue scales and nasal lavages were performed to determine histamine and lysozyme levels. RESULTS: The two groups reacted differently to CDA: after the challenge, patients with rhinitis and asthma reported significantly higher scores for nasal congestion, rhinorrhea and lacrimation. Also in this group, significant increases in histamine and in lysozyme levels in nasal lavage fluids were induced by CDA. In subjects with rhinitis alone, CDA failed to increase histamine or lysozyme levels above baseline. The CDA-induced change from baseline in histamine was significantly higher in the patients with rhinitis and asthma, compared with the rhinitis-only group. CONCLUSION: Patients with AR and asthma have stronger nasal responsiveness to CDA compared with patients with rhinitis alone. This observation is consistent with the notion that compared with rhinitis alone, the presence of asthma and rhinitis signifies a higher degree of functional abnormality of the entire airway.

Clinical features and short-term outcomes of 144 patients with SARS in the greater Toronto area.

CONTEXT: Severe acute respiratory syndrome (SARS) is an emerging infectious disease that first manifested in humans in China in November 2002 and has subsequently spread worldwide. OBJECTIVES: To describe the clinical characteristics and short-term outcomes of SARS in the first large group of patients in North America; to describe how these patients were treated and the variables associated with poor outcome. DESIGN, SETTING, AND PATIENTS: Retrospective case series involving 144 adult patients admitted to 10 academic and community hospitals in the greater Toronto, Ontario, area between March 7 and April 10, 2003, with a diagnosis of suspected or probable SARS. Patients were included if they had fever, a known exposure to SARS, and respiratory symptoms or infiltrates observed on chest radiograph. Patients were excluded if an alternative diagnosis was determined. MAIN OUTCOME MEASURES: Location of exposure to SARS; features of the history, physical examination, and laboratory tests at admission to the hospital; and 21-day outcomes such as death or intensive care unit (ICU) admission with or without mechanical ventilation. RESULTS: Of the 144 patients, 111 (77%) were exposed to SARS in the hospital setting. Features of the clinical examination most commonly found in these patients at admission were self-reported fever (99%), documented elevated temperature (85%), nonproductive cough (69%), myalgia (49%), and dyspnea (42%). Common laboratory features included elevated lactate dehydrogenase (87%), hypocalcemia (60%), and lymphopenia (54%). Only 2% of patients had rhinorrhea. A total of 126 patients (88%) were treated with ribavirin, although its use was associated with significant toxicity, including hemolysis (in 76%) and decrease in hemoglobin of 2 g/dL (in 49%). Twenty-nine patients (20%) were admitted to the ICU with or without mechanical ventilation, and 8 patients died (21-day mortality, 6.5%; 95% confidence interval [CI], 1.9%-11.8%). Multivariable analysis showed that the presence of diabetes (relative risk [RR], 3.1; 95% CI, 1.4-7.2; P =.01) or other comorbid conditions (RR, 2.5; 95% CI, 1.1-5.8; P =.03) were independently associated with poor outcome (death, ICU admission, or mechanical ventilation). CONCLUSIONS: The majority of cases in the SARS outbreak in the greater Toronto area were related to hospital exposure. In the event that contact history becomes unreliable, several features of the clinical presentation will be useful in raising the suspicion of SARS. Although SARS is associated with significant morbidity and mortality, especially in patients with diabetes or other comorbid conditions, the vast majority (93.5%) of patients in our cohort survived.

The Fun, Food, and Fitness Project (FFFP): the Baylor GEMS pilot study.

OBJECTIVE: The Girls health Enrichment Multisite Studies (GEMS) Fun, Food, and Fitness Project (FFFP) was designed to prevent obesity among 8-year-old African-American girls. DESIGN: Twelve-week, two-arm parallel group randomized controlled pilot study. SETTING: Summer day camp and homes in Houston, Texas. PARTICIPANTS: Thirty-five girls and their parents or caregivers were randomly assigned to treatment (N=19) or control groups (N=16). INTERVENTION: Girls in the intervention group attended a special 4-week summer day camp, followed by a special 8-week home Internet intervention for the girls and their parents. Control group girls attended a different 4-week summer day camp, followed by a monthly home Internet intervention, neither of which components included the GEMS-FFFP enhancements. MAIN OUTCOME MEASURES: Body mass index (BMI), consumption of fruit, 100% fruit juice, and vegetables (FJV), physical activity. RESULTS: After adjusting for baseline BMI, there were no significant differences in BMI between treatment and control group girls, either at the end of the 4-week summer day camp, or after the full 12-week intervention. By the end of the summer camp, the subgroup of treatment group girls heavier at baseline exhibited a trend (P<.08) toward lower BMI, compared to their heavier counterparts in the control group. Overall results at the end of the 12-week program demonstrated substantial, although not significant, differences between treatment and control groups in the hypothesized directions. On average, less than half the treatment sample logged onto the Website, which limited intervention dose. CONCLUSIONS: Summer day camp appears to offer promise for initiating health behavior change. Effective methods must be developed and tested to enhance log-on rates among healthy children and their parents before Internet programs can achieve their potential.