Neutrophil chemotaxis and receptor expression in clinical septic shock

Objective To examine the hypothesis that neutrophil chemotaxis to interleukin-8 (IL-8) is reduced in septic shock. Surface expression of neutrophil CXC chemokine receptors and the adhesion molecule CD11b were also examined and associations between disease severity, gas exchange and receptor expression were studied.Design Prospective cohort clinical study.Setting Intensive care unit in a tertiary referral teaching hospital.Patients Patients with septic shock (n=15) and healthy controls (n=8) were studied.Measurements and results Daily (for 5 consecutive days) flow cytometric measurements of chemokine and integrin surface expression. In vitro neutrophil chemotaxis to IL-8 was also compared between patients with sepsis and healthy controls. CXCR2 expression significantly fell, CD11b expression increased and CXCR1 expression was unchanged throughout the study in the septic group compared with healthy controls. CD11b positively correlated with increasing APACHE II scores (p<0.0001) and worsening PaO₂/FIO₂ ratios (p<0.0001). CXCR2 expression negatively correlated with both APACHE II scores (p=0.016) and PaO₂/FIO₂ ratios (p=0.01). There was no correlation between CXCR1 expression and either APACHE II score or PaO₂/FIO₂ ratios. Chemotaxis to IL-8 was reduced in patients with sepsis compared with healthy volunteers.Conclusions Surface expression of the chemokine receptor CXCR2 and the -integrin CD11b, but not CXCR1, were reduced on neutrophils isolated from patients with septic shock compared with healthy controls. Chemotaxis to IL-8 was also reduced in neutrophils from septic patients compared with healthy controls. The changes in receptor expression correlated with measures of disease severity.     

Spontaneous resolution of infantile nephrotic syndrome

Congenital nephrosis is a rare disease with universally accepted poor prognosis; despite developments in the pathogenesis and management, these children are always a challenge to the caregivers and families. Reported here, is a case of a 6-month-old female infant with infantile nephrotic syndrome, who went into spontaneous resolution within a week without therapy and remained asymptomatic for the following 2 years.     

A third ventricular meningioma in a child

A case is presented of a 10-year-old boy with von Recklinghausen's syndrome and multiple meningiomas, one of which was in the third ventricle. The investigation and management of the case is discussed.     

Intentional injury mortality in the European Union: how many more lives could be saved?

OBJECTIVE: To explore the scope for reducing the number of intentional injury deaths, hypothesizing that all European Union (EU) countries are able to match the experience of the country with the lowest mortality rate for intentional injuries. DESIGN: Intentional injury mortality data for the three last available years and denominator population estimates were obtained from the World Health Organisation mortality database for the 22 EU countries with more than one million population. To estimate the potential saving of lives, the yearly average age adjusted injury mortality rates were calculated. This issue done for children (0-14), adults (15-64), and elderly people (65 and over), both including and excluding deaths from undetermined cause. MAIN OUTCOME MEASURES: Number of lives that might potentially be saved if all EU member states matched the lowest intentional injury rate reported by an EU member state. RESULTS: Over 73% of all intentional injury deaths could have been avoided if all EU countries matched the country with the lowest intentional injury mortality rate. EU member states would have suffered about 600 fewer intentional injury deaths in children, about 40 000 fewer adult deaths, and over 14 000 fewer intentional injury deaths in the elderly. This amounts to over 55 000 lives in a single year. CONCLUSIONS: Many lives lost through injury might be saved if all countries were to achieve the lowest intentional injury mortality rates reported in the EU. How this theoretical observation might be translated into practice needs to be further explored as the international variation in intentional injury mortality rates in the EU results from a range of factors.     

The antidiabetic effect of Geigeria alata is mediated by enhanced insulin secretion, modulation of β-cell function, and improvement of antioxidant activity in streptozotocin-induced diabetic rats

In Sudanese folk medicine, Geigeria alata roots have been used for the management of diabetes for a long time. However, its antidiabetic activity is unreported. In this study, G. alata methanolic extract was tested for its antidiabetic, antioxidant, and β-cell modulatory effects in a streptozotocin-induced diabetic rat model. In this model of diabetic rats, the oral glucose tolerance test with G. alata extract at 125, 250, and 500?mg/kg doses revealed the efficacy of the 250?mg/kg dose in improving glucose tolerance comparable to the standard drug glibenclamide. Diabetic rats were treated with a 250?mg/kg dose of G. alata extract orally for 2?h (acute) or 14 days (chronic). In the case of acute treatment, the extract lowered blood glucose levels significantly at 120?min both in nondiabetic and diabetic rats. Chronic treatment of diabetic rats with 250?mg/kg of G. alata extract resulted in a significant decrease in blood glucose level closer to that of nondiabetic rats. Interestingly, increased serum insulin, improved β-cell function, and antioxidant status were observed in G. alata-treated diabetic rats. G. alata also showed strong antioxidant and α-glucosidase inhibitory activities in in vitro assays. These data show direct evidence that G. alata has antidiabetic activity and suggest that the antidiabetic activity is due to enhanced insulin secretion, modulation of β-cell function, and improvement of antioxidant status.     

Calpain-mediated regulation of platelet signaling pathways

PURPOSE OF REVIEW: There is considerable interest in understanding the function and mechanism of calpains in platelet aggregation, spreading, and granular secretion pathways. Recent insights from the calpain-1 knockout platelets suggest a pivotal role of these cysteine proteases in the regulation of outside-in signaling, aggregation, and clot retraction. RECENT FINDINGS: The calpain-1 knockout mouse provided direct evidence for the role of calpain-1 in platelet aggregation and clot retraction. Reduced tyrosine phosphorylation of platelet proteins correlated with reduced platelet aggregation and clot retraction. Future investigations of the mechanism of platelet defects in calpain-1 null mice may unveil the physiological functions of this important and elusive protease in mammalian cells. SUMMARY: This review focuses on the role of calpains in platelets with a particular emphasis on recent findings in calpain-1 null platelets. Previous studies used synthetic inhibitors to study the role of calpains in platelet function yielding useful information about the identification of calpain substrates. The development of calpain-1 null mice demonstrated that calpain-1 plays an important function in the regulation of platelet aggregation and clot retraction. Since the combined deletion of calpain-1 and calpain-2 genes results in embryonic lethality, the calpain-1 null mouse remains the only experimental model available to study the physiological role of calpains in mammalian cells.     

Combined transhepatic and transjugular approach for mechanical thrombectomy of massive TIPS thrombosis

Transjugular intrahepatic portosystemic shunt (TIPS) is a well-validated decompressive therapy option to manage ascites and variceal bleeding secondary to portal hypertension. Complications following TIPS procedures include hepatic encephalopathy, liver failure, and TIPS dysfunction. TIPS dysfunction is due to occlusion or stenosis of the TIPS shunt and can be caused by acute or chronic thrombosis. TIPS thrombosis is often treated with mechanical thrombectomy or catheter-directed thrombolytic therapy. Most cases of in-stent occlusion can be treated via a transjugular approach with recanalization or placement of additional stents. We present a case of a 72-year-old female who presented with worsening ascites 17 months after initial TIPS procedure; she was found to have a large thrombus completely occluding the TIPS stent. In our case, a combined transhepatic and transjugular approach was required for TIPS revision given the extent of well-organized clot located near the hepatic venous end of the stent, resulting from prolonged stent occlusion. This was an extremely challenging scenario with two overlapping covered stents and a bare metal stent at the hepatic venous end in the setting of chronic thrombosis and a well-organized fibrous cap. The case highlights the need for optimal initial placement of the primary TIPS shunt to avoid the need for subsequent complex interventions to maintain TIPS shunt patency.