Postprandial induction of chaperone gene expression is rapid in mice.

Molecular chaperones assist in the biosynthesis and processing of proteins. Most chaperones are induced by physiological stresses. We have shown that dietary energy restriction decreases the mRNA and protein levels of many endoplasmic reticulum chaperones in the livers of mice. Here, we have investigated the response of chaperone mRNA to feeding. Control and 50% energy-restricted C3B10RF1 mice were deprived of food for 24 h, fed, and killed 0, 1.5, 5 or 12 h after feeding. Chaperone mRNAs were strongly induced as early as 1.5 h after feeding in control and energy-restricted mice. The integrated levels of these mRNA over 24 h were significantly lower in energy-restricted mice. The mRNA response to energy intake was mirrored over the course of days in the level of chaperone protein. A similar but smaller response to feeding was found in kidney and muscle. Puromycin and cycloheximide failed to inhibit the feeding response, suggesting that feeding releases chaperone expression from an unstable inhibitor. Studies with dibutyryl-cAMP- and glucagon-supplemented, normal and streptozotocin-diabetic mice suggest that glucagon and insulin may be mediators of the feeding response. Adrenalectomy enhanced the feeding induction, but dexamethasone administration had no effect. Thus, postprandial changes in insulin and glucagon may link chaperone gene expression to feeding, possibly in several tissues including liver.     

Fluconazole dosing in continuous veno-venous haemofiltration (CVVHF): need for a high daily dose of 800 mg

To cover intermediate sensitive Candida glabrata in ICU patients,fluconazole plasma peak levels at least in the range of 16–32µg/ml appear necessary for treatment. Previous studiesdid not reach these fluconazole levels under continuous veno-venoushaemofiltration (CVVHF) with dosages of 200–600 mg fluconzoledaily. In the present study, nine patients simultaneously requiringCVVHF for treatment of acute oligoanuric renal failure and antimycotictherapy of Candida septicemia received fluconazole 800 mg/day.Fluconazole plasma levels were determined to evaluate whetherthis dosage is adequate to reach the advised fluconazole levels.Patients were dialysed on two consecutive days with an ultrafiltrationrate (UF) of 1000 ml/h or 2000 ml/h, respectively, in a randomizedorder. The predilution was 800 ml/h and 1800 ml/h, respectively.The treatment was tolerated without adverse effects. All patientsreached plasma fluconazole concentrations between 16 and 32µg/ml, remaining in this range for a minimum of 1 up to24 h with a mean of 9.6 h and a UF rate of 2000 ml/h, and 15.7h with a UF rate of 1000 ml/h. So far, there are no in vivodata on the fluconazole plasma concentrations required for effectivetreatment. However, our data demonstrate, that at least thefluconazole concentrations desirable on the basis of in vitrosusceptibility testing can be reached in critically ill patientson CVVHF in an ICU setting. However, in these patients, 800mg fluconazole/day are necessary to achieve fungicidal drugconcentrations.     

Prognostic score systems and community-acquired bacteraemic pneumococcal pneumonia.

The aim of this study was to evaluate the accuracy of three score systems: the pneumonia severity index (PSI); CURB-65 (confusion; urea >7 mM; respiratory rate > or =30 breaths x min(-1); blood pressure <90 mmHg systolic or < or =60 mmHg diastolic; aged > or =65 yrs old); and modified American Thoracic Society rule for predicting intensive care unit (ICU) need and mortality due to bacteraemic pneumococcal pneumonia. All adult patients (n = 114) with invasive pneumococcal pneumonia at the Karolinska University Hospital, Sweden, 1999-2000, were included in the study. Severity scores were calculated and the independent prognostic importance of different variables was analysed by multiple regression analyses. PSI > or = IV, CURB-65 > or = 2, and the presence of one major or more than one minor risk factor in mATS all had a high sensitivity, but somewhat lower specificity for predicting death and ICU need. The death rate was 12% (13 out of 114). Severity score and treatment in departments other than the Dept of Infectious Diseases were the only factors independently correlated to death. Patients treated in other departments more often had severe underlying illnesses and were more severely ill on admission. However, a significant difference in death rates remained after adjustment for severity between the two groups. In conclusion, all score systems were useful for predicting the need for intensive care unit treatment and death due to bacteremic pneumococcal pneumonia. The pneumonia severity index was the most sensitive, but CURB-65 was easier to use.     

Komplexverletzungen des Fußes

Complex injuries of the foot are often overlooked, especially in the multiple injured patient, and they then lead to major loss of function. When the mechanism of injury suggests involvement of the foot, a clinical examination of the lower extremities should be included in the primary diagnostic procedures implemented in the multiply injured patient, followed by radiological examination once the patient's condition is stable. The condition of the soft tissues is of decisive importance in the prognosis of complex foot injuries, regardless of whether the damage to the foot is one component of a polytrauma or an isolated injury, which can also be life threatening. The diagnostic examinations selected should be adapted to the severity of the injuries in the particular multiply injured patient. Successful therapy involves stable internal fixation of injuries to bones and joints, though the external fixation options should be considered in the first instance, and carefully selected methods of temporary and definitive soft tissue reconstruction. The aim of treatment is the best possible reconstruction of the foot as a functional weight-bearing unit with intact soft tissue cover and a natural form. Good results can be achieved when there is close interdisciplinary cooperation between trauma (orthopedic) and plastic surgeons. Patient with severe injuries of this kind should be transferred to a trauma center as the first step toward this end.     

Muscular strength and bone mineral density in haemodialysis patients

Purpose. The objective of this study was to determine the relationship between muscular strength and bone mineral density (BMD) in patients undergoing regular haemodialysis. Methods. The BMD was measured in the lumbar spine (L2L4) and in the proximal femur (femoral neck and trochanter) with dual-energy X-ray absorptiometry (DEXA (Lunar DPX). Muscular strength of the extensors, flexors and abductors muscles of the femur (proximal muscles) and extensors muscles of the back was measured with an isometric cynamometer. Thirty patients, 15 women with a mean age of 33.7 years (18-43) and 15 men with a mean age of 15.5 years (18-65) were included in the study. Results. There was a positive and significant correlation between the BMD of the femoral neck and muscular strength of the flexors (r=0.490, P<0.005), the extensors (r=0.658, P<0.01) and the abductors muscles of the femur (r=0.671, P <0.0008), as well as between the muscular strength of the flexors (r=0.413, P <0.02) and extensors muscles of the femur (r=0.433, P <0.01) with BMD of the trochanter. There was no correlation between the muscular strength of the back extensor muscles and the BMD of the lumbar spine (r=-0.119, P NS). There was no correlation between the BMD and the number of years of haemodialysis therapy (r=-0.032, P NS), the patient's age (r=-159, P NS), or the value of serum PTH (r=0.369, P NS) respectively. However, there was a significant correlation between the BMD of the femoral neck with muscular strength (r=0.602, P <0.05). Conclusion. This study reveals the close relationship that exists between muscular strength of the proximal muscles and the BMD of proximal femur in patients undergoing haemodialysis.     

Peanut-induced anaphylaxis in children and adolescents: Data from the European Anaphylaxis Registry

Background

Peanut allergy has a rising prevalence in high-income countries, affecting 0.5%–1.4% of children. This study aimed to better understand peanut anaphylaxis in comparison to anaphylaxis to other food triggers in European children and adolescents.

Methods

Data was sourced from the European Anaphylaxis Registry via an online questionnaire, after in-depth review of food-induced anaphylaxis cases in a tertiary paediatric allergy centre.

Results

3514 cases of food anaphylaxis were reported between July 2007 - March 2018, 56% in patients younger than 18 years. Peanut anaphylaxis was recorded in 459 children and adolescents (85% of all peanut anaphylaxis cases). Previous reactions (42% vs. 38%; p = .001), asthma comorbidity (47% vs. 35%; p < .001), relevant cofactors (29% vs. 22%; p = .004) and biphasic reactions (10% vs. 4%; p = .001) were more commonly reported in peanut anaphylaxis. Most cases were labelled as severe anaphylaxis (Ring&Messmer grade III 65% vs. 56% and grade IV 1.1% vs. 0.9%; p = .001). Self-administration of intramuscular adrenaline was low (17% vs. 15%), professional adrenaline administration was higher in non-peanut food anaphylaxis (34% vs. 26%; p = .003). Hospitalization was higher for peanut anaphylaxis (67% vs. 54%; p = .004).

Conclusions

The European Anaphylaxis Registry data confirmed peanut as one of the major causes of severe, potentially life-threatening allergic reactions in European children, with some characteristic features e.g., presence of asthma comorbidity and increased rate of biphasic reactions. Usage of intramuscular adrenaline as first-line treatment is low and needs to be improved. The Registry, designed as the largest database on anaphylaxis, allows continuous assessment of this condition.