A case of septicaemic anthrax in an intravenous drug user

<p><b>Background:</b> In 2000, Ringertz et al described the first case of systemic anthrax caused by injecting heroin contaminated with anthrax. In 2008, there were 574 drug related deaths in Scotland, of which 336 were associated with heroin and or morphine. We report a rare case of septicaemic anthrax caused by injecting heroin contaminated with anthrax in Scotland.</p> <p><b>Case Presentation:</b> A 32 year old intravenous drug user (IVDU), presented with a 12 hour history of increasing purulent discharge from a chronic sinus in his left groin. He had a tachycardia, pyrexia, leukocytosis and an elevated C-reactive protein (CRP). He was treated with Vancomycin, Clindamycin, Ciprofloxacin, Gentamicin and Metronidazole. Blood cultures grew Bacillus anthracis within 24 hours of presentation. He had a computed tomography (CT) scan and magnetic resonance imagining (MRI) of his abdomen, pelvis and thighs performed. These showed inflammatory change relating to the iliopsoas and an area of necrosis in the adductor magnus.</p> <p>He underwent an exploration of his left thigh. This revealed chronically indurated subcutaneous tissues with no evidence of a collection or necrotic muscle. Treatment with Vancomycin, Ciprofloxacin and Clindamycin continued for 14 days. Negative Pressure Wound Therapy (NPWT) device was applied utilising the Venturi™ wound sealing kit. Following 4 weeks of treatment, the wound dimensions had reduced by 77%.</p> <p><b>Conclusions:</b> Although systemic anthrax infection is rare, it should be considered when faced with severe cutaneous infection in IVDU patients. This case shows that patients with significant bacteraemia may present with no signs of haemodynamic compromise. Prompt recognition and treatment with high dose IV antimicrobial therapy increases the likelihood of survival. The use of simple wound therapy adjuncts such as NPWT can give excellent wound healing results.</p&gt

Potential role of PC-1 expression and pyrophosphate elaboration in the molecular etiology of the FGFR-associated craniosynostosis syndromes

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73652/1/j.1601-6343.2007.00387.x.pd

What Parents of Children Who Have Received Emergency Care Think about Deferring Consent in Randomised Trials of Emergency Treatments: Postal Survey

OBJECTIVE: To investigate parents' views about deferred consent to inform management of trial disclosure after a child's death. METHODS: A postal questionnaire survey was sent to members of the Meningitis Research Foundation UK charity, whose child had suffered from bacterial meningitis or meningococcal septicaemia within the previous 5 years. Main outcome measures were acceptability of deferred consent; timing of requesting consent; and the management of disclosure of the trial after a child's death. RESULTS: 220 families were sent questionnaires of whom 63 (29%) were bereaved. 68 families responded (31%), of whom 19 (28%) were bereaved. The majority (67%) was willing for their child to be involved in the trial without the trial being explained to them beforehand; 70% wanted to be informed about the trial as soon as their child's condition had stabilised. In the event of a child's death before the trial could be discussed the majority of bereaved parents (66% 12/18) anticipated wanting to be told about the trial at some time. This compared with 37% (18/49) of non-bereaved families (p = 0.06). Parents' free text responses indicated that the word 'trial' held strongly negative connotations. A few parents regarded gaps in the evidence base about emergency treatments as indicating staff lacked expertise to care for a critically ill child. Bereaved parents' free text responses indicated the importance of individualised management of disclosure about a trial following a child's death. DISCUSSION: Deferred consent is acceptable to the majority of respondents. Parents whose children had recovered differed in their views compared to bereaved parents. Most bereaved parents would want to be informed about the trial in the aftermath of a child's death, although a minority strongly opposed such disclosure. Distinction should be drawn between the views of bereaved and non-bereaved parents when considering the acceptability of different consent processes

Association of kidney function with inflammatory and procoagulant markers in a diverse cohort: A cross-sectional analysis from the Multi-Ethnic Study of Atherosclerosis (MESA)

Background: Prior studies using creatinine-based estimated glomerular filtration rate (eGFR) have found limited associations between kidney function and markers of inflammation. Using eGFR and cystatin C, a novel marker of kidney function, the authors investigated the association of kidney function with multiple biomarkers in a diverse cohort. Methods: The Multi-Ethnic Study of Atherosclerosis consists of 6,814 participants of white, African-American, Hispanic, and Chinese descent, enrolled from 2000-2002 from six U.S. communities. Measurements at the enrollment visit included serum creatinine, cystatin C, and six inflammatory and procoagulant biomarkers. Creatinine-based eGFR was estimated using the fourvariable Modification of Diet in Renal Disease equation, and chronic kidney disease was defined by an eGFR less than 60 mL/min/1.73 m2. Results: Adjusted partial correlations between cystatin C and all biomarkers were statistically significant: C-reactive protein (r = 0.08), interleukin-6 (r = 0.16), tumor necrosis factor-a soluble receptor 1 (TNF-aR1; r = 0.75), intercellular adhesion molecule-1 (r = 0.21), fibrinogen (r = 0.14), and factor VIII (r = 0.11; two-sided p less than 0.01 for all). In participants without chronic kidney disease, higher creatinine-based eGFR was associated only with higher TNF-aR1 levels. Conclusion: In a cohort characterized by ethnic diversity, cystatin C was directly associated with multiple procoagulant and inflammatory markers. Creatinine-based eGFR had similar associations with these biomarkers among subjects with chronic kidney disease.This research was supported by contracts N01-HC-95159 through N01-HC-95169 from the National Heart, Lung, and Blood Institute (NHLBI)

Assessment of soy phytoestrogens' effects on bone turnover indicators in menopausal women with osteopenia in Iran: a before and after clinical trial

BACKGROUND: Osteoporosis is the gradual declining in bone mass with age, leading to increased bone fragility and fractures. Fractures in hip and spine are known to be the most important complication of the disease which leads in the annual mortality rate of 20% and serious morbidity rate of 50%. Menopause is one of the most common risk factors of osteoporosis. After menopause, sex hormone deficiency is associated with increased remodeling rate and negative bone balance, leading to accelerated bone loss and micro-architectural defects, resulting into increased bone fragility. Compounds with estrogen-like biological activity similar to "Isoflavones" present in plants especially soy, may reduce bone loss in postmenopausal women as they are similar in structure to estrogens. This research, therefore, was carried out to study the effects of Iranian soy protein on biochemical indicators of bone metabolism in osteopenic menopausal women. MATERIALS AND METHODS: This clinical trial of before-after type was carried out on 15 women 45–64 years of age. Subjects were given 35 g soy protein per day for 12 weeks. Blood and urine sampling, anthropometric measurement and 48-h-dietary recalls were carried out at zero, 6 and 12 weeks. Food consumption data were analyzed using Food Proccessor Software. For the study of bone metabolism indicators and changes in anthropometric data as well as dietary intake, and repeated analyses were employed. RESULTS: Comparison of weight, BMI, physical activity, energy intake and other intervening nutrients did not reveal any significant changes during different stages of the study. Soy protein consumption resulted in a significant reduction in the urinary deoxypyridinoline and increasing of total alkaline phosphatase (p < 0.05), although the alterations in osteocalcin, c-telopeptide, IGFBP3 and type I collagen telopeptide were not significant. CONCLUSION: In view of beneficial effect of soy protein on bone metabolism indicators, inclusion of this relatively inexpensive food in the daily diet of menopausal women, will probably delay bone resorption, thereby preventing osteoporosis

Association of sICAM-1 and MCP-1 with coronary artery calcification in families enriched for coronary heart disease or hypertension: the NHLBI Family Heart Study

<p>Abstract</p> <p>Background</p> <p>Data accumulated from mouse studies and in vitro studies of human arteries support the notion that soluble intercellular adhesion molecule-1 (sICAM-1) and monocyte chemoattractant protein-1 (MCP-1) play important roles in the inflammation process involved in atherosclerosis. However, at the population level, the utility of sICAM-1 and MCP-1 as biomarkers for subclinical atherosclerosis is less clear. In the follow-up exam of the NHLBI Family Heart Study, we evaluated whether plasma levels of sICAM-1 and MCP-1 were associated with coronary artery calcification (CAC), a measure of the burden of coronary atherosclerosis.</p> <p>Methods</p> <p>CAC was measured using the Agatston score with multidetector computed tomography. Information on CAC and MCP-1 was obtained in 2246 whites and 470 African Americans (mean age 55 years) without a history of coronary heart disease (CHD). Information on sICAM-1 was obtained for white participants only.</p> <p>Results</p> <p>In whites, after adjustment for age and gender, the odds ratios (ORs) of CAC (CAC > 0) associated with the second, third, fourth, and fifth quintiles of sICAM-1 compared to the first quintile were 1.22 (95% confidence interval [CI]: 0.91–1.63), 1.15 (0.84–1.58), 1.49 (1.09–2.05), and 1.72 (1.26–2.36) (p = 0.0005 for trend test), respectively. The corresponding ORs for the second to fifth quintiles of MCP-1 were 1.26 (0.92–1.73), 0.99 (0.73–1.34), 1.42 (1.03–1.96), and 2.00 (1.43–2.79) (p < 0.0001 for trend test), respectively. In multivariable analysis that additionally adjusted for other CHD risk factors, the association of CAC with sICAM-1 and MCP-1 was attenuated and no longer statistically significant. In African Americans, the age and gender-adjusted ORs of CAC associated with the second and third tertiles of MCP-1 compared to the first tertile were 1.16 (0.64–2.08) and 1.25 (0.70–2.23) (p = 0.44 for trend test), respectively. This result did not change materially after additional adjustment for other CHD risk factors. Test of race interaction showed that the magnitude of association between MCP-1 and CAC did not differ significantly between African Americans and whites. Similar results were obtained when CAC ≥ 10 was analyzed as an outcome for both MCP-1 and sICAM-1.</p> <p>Conclusion</p> <p>This study suggests that sICAM-1 and MCP-1 are biomarkers of coronary atherosclerotic burden and their association with CAC was mainly driven by established CHD risk factors.</p

Genome-Wide Association Analysis of Soluble ICAM-1 Concentration Reveals Novel Associations at the NFKBIK, PNPLA3, RELA, and SH2B3 Loci

Soluble ICAM-1 (sICAM-1) is an endothelium-derived inflammatory marker that has been associated with diverse conditions such as myocardial infarction, diabetes, stroke, and malaria. Despite evidence for a heritable component to sICAM-1 levels, few genetic loci have been identified so far. To comprehensively address this issue, we performed a genome-wide association analysis of sICAM-1 concentration in 22,435 apparently healthy women from the Women's Genome Health Study. While our results confirm the previously reported associations at the ABO and ICAM1 loci, four novel associations were identified in the vicinity of NFKBIK (rs3136642, P = 5.4×10−9), PNPLA3 (rs738409, P = 5.8×10−9), RELA (rs1049728, P = 2.7×10−16), and SH2B3 (rs3184504, P = 2.9×10−17). Two loci, NFKBIB and RELA, are involved in NFKB signaling pathway; PNPLA3 is known for its association with fatty liver disease; and SH3B2 has been associated with a multitude of traits and disease including myocardial infarction. These associations provide insights into the genetic regulation of sICAM-1 levels and implicate these loci in the regulation of endothelial function

17β-Estradiol Prevents Early-Stage Atherosclerosis in Estrogen Receptor-Alpha Deficient Female Mice

Estrogen is atheroprotective and a high-affinity ligand for both known estrogen receptors, ERα and ERβ. However, the role of the ERα in early-stage atherosclerosis has not been directly investigated and is incompletely understood. ERα-deficient (ERα−/−) and wild-type (ERα+/+) female mice consuming an atherogenic diet were studied concurrent with estrogen replacement to distinguish the actions of 17β-estradiol (E2) from those of ERα on the development of early atherosclerotic lesions. Mice were ovariectomized and implanted with subcutaneous slow-release pellets designed to deliver 6 or 8 μg/day of exogenous 17β-estradiol (E2) for a period of up to 4 months. Ovariectomized mice (OVX) with placebo pellets (E2-deficient controls) were compared to mice with endogenous E2 (intact ovaries) and exogenous E2. Aortas were analyzed for lesion area, number, and distribution. Lipid and hormone levels were also determined. Compared to OVX, early lesion development was significantly (p < 0.001) attenuated by E2 with 55–64% reduction in lesion area by endogenous E2 and >90% reduction by exogenous E2. Compared to OVX, a decline in lesion number (2- to 4-fold) and lesser predilection (~4-fold) of lesion formation in the proximal aorta also occurred with E2. Lesion size, development, number, and distribution inversely correlated with circulating plasma E2 levels. However, atheroprotection was independent of ERα status, and E2 athero-protection in both genotypes was not explained by changes in plasma lipid levels (total cholesterol, triglyceride, and high-density lipoprotein cholesterol). The ERα is not essential for endogenous/exogenous E2-mediated protection against early-stage atherosclerosis. These observations have potentially significant implications for understanding the molecular and cellular mechanisms and timing of estrogen action in different estrogen receptor (ER) deletion murine models of atherosclerosis, as well as implications to human studies of ER polymorphisms and lipid metabolism. Our findings may contribute to future improved clinical decision-making concerning the use of hormone therapy